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I I

P OPOEI
010

Volume III

lliQfI'lVlllit

Government of India
Ministry of Health & Family Welfare

Published by
THE INDIAN PHARMACOPOEIA COMMISSION
GHAZIABAD
© 2010, Indian Pharmacopoeia Commission
Application for reproduction should be made to
The Secretary-cum-Scientific Director
INDIAN PHAR1vlACOPOEIA COMMISSION
Sector-23, Raj Nagar,
Ghaziabad-201 002, India
Tel: (91-120)-2783401
Fax: (91-120)-2783311
Website: www.ipc.gov.in
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ISBN 81-903436-8-8 (Vol. III)


ISBN 81-903436-9-6 (Set)

Sixth Edition (6.0)


Effective from 1st September, 2010

On behalfof Government of India


Ministry ofHealth & Family Welfare

Designed, produced & published by The Indian Pharmacopoeia Commission


Indian Pharmacopoeia Laboratory
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ISBN 81-903436-8-8 ISBN 81-903436-9-6

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INDIAN
PHARMACOPOEIA
2010

Volume III
INDIAN PHARMACOPOEIA 2010

CONTENTS

VOLUME I
Notices v
Preface Vl1

Indian Pharmacopoeia Commission IX

Acknowledgements xv
Introduction XVl1

General Chapters 7

VOLUME II
General Notices 711
General Monographs on Dosage Forms 719
Monographs on Drug substances, Dosage forms and
Pharmaceutical aids (A to M) 755

VOLUME III
General Notices 1729
Monographs on Drug substances, Dosage forms and
Pharmaceutical aids (N to Z) 1737
Monographs on Vaccines and Immunosera for Human Use 2345
Monographs on Herbs and Herbal Products 2463
Monographs on Blood and Blood-related Products 2555
Monographs on Biotechnology Products 2591
Monographs on Veterinary Products 2619
Index 2755

1725
INDIAN PHARMACOPOEIA 2007

VolumeIIl
CONTENTS

VOLUME 3

General Notices 1729


Monographs on Drug substances, Dosage fOTITIS and
Phannaceutical aids (N to Z) 1737
Monographs on Vaccines and Immunosera for Human Use 2345
Monographs on Herbs andHerbal Products 2463
Monographs on Blood and Blood-related Products 2555
Monographs on Biotechnology Products 2591
Monographs on Veterinary Products 2619
Index 2755

1727
INDIAN PHARMACOPOEIA 2010 GENERAL NOTICES

GENERAL NOTICES

General Statements 1731


Name 1731
Official and OfficialArticles 1731
Official Standards 1731
Added Substances 1731
Alternative Methods 1731
Meanings ofTerms 1732
Provisions Applicable to Monographs and Test Methods 1732
Expression ofContents 1732
Expression ofConcentrations 1732
Abbreviated Statements ~ ... 1732
Weights and Measures 1733
Monographs 1733
General Monographs 1733
Production 1733
Manufacture ofDrug Products 1733
Excipients 1" ••• 1733
Individual Monographs 1733
Titles 1733
Chemical Formulae 1733
Atomic and Molecular Weights 1733
Definitions 1733
Statement ofContent 1734
Category 1734
Dose 1734
Usual Strength 1734
Description 1734
Solubility 1734
Test Methods 1734
Identification 1734

1729
GENERAL NOTICES INDIAN PHARMACOPOEIA 2010

Tests and Assays 1734


Tests 1734
Other Tests 1735
Limits 1735
Quantities 1735
Apparatus 1735
Reagents and Solutions 1735
fudicators 1735
Reference Substances 1735
TestsAnimals 1735
Calculation ofResults 1735
Storage 1736
Storage Containers 1736
Labelling 1736

1730
IP 2010 GENERAL NOTICES

General Notices use but not necessarily to articles that may be sold under the
same name for other purposes.
The active pharmaceutical ingredients (drug substances),
General Statements
excipients (pharmaceutical aids), phannaceutical preparations
The General Notices provide the basic guidelines for the (dosage forms) and other articles described in the monographs
interpretation and application of the standards, tests, assays, are intended for human and veterinary use (unless explicitly
and other specifications of the Indian Phannacopoeia (IP), as restricted to one of these uses).
well as to the statements made in the monographs and other The requirements given in the monographs are not framed to
texts of the Phannacopoeia. provide against all possible impurities, contaminants or
A monograph is to be constructed in accordance with any adulterants; they provide appropriate limitation of potential
general monograph or notice or any appendix, note or other impurities only.
explanatory material that is contained in this Phannacopoeia A preparation must comply throughout the shelf-life assigned
and that is applicable to that monograph. All statements to it by the manufacturer; for opened or broached containers
contained in the monograph, except where a specific general the maximum period of validity for use may sometimes be
notice indicates otherwise and with the exceptions given stated in the individual monograph. Nevertheless, the
hereafter, constitute standards for the official articles. An article responsibility for assigning the period of validity shall be
is not ofpharmacopoeial quality unless it complies with all of with the manufacturer.
the requirements stated.
Added Substances. An official substance, as distinguished
Exceptions to the General Notices do exist, and where they from an official preparation, contains no added substances
do, the wording in the individual monograph or an appendix except when specifically pennitted in the individual monograph.
takes precedence and specifically indicates directions or the Unless otherwise specified in the individual monograph, or
intent. Thus, the specific wording of standards, tests, assays elsewhere in the General Notices, suitable substances may be
and other specifications is binding wherever deviations from added to an official preparation to enhance its stability,
the General Notices exist. Likewise, where there is no specific usefulness or elegance, or to facilitate its preparation. Such
mention to the contrary, the General Notices apply. auxiliary substances shall be hannless in the amounts used,
shall not exceed the minimum quantity required to provide
Name. The full name or title ofthis book, including addenda their intended effect, shall not impair the therapeutic'efficacy
thereto, is Indian Phannacopoeia 2010, abbreviated to IP 2010. or the bioavailability or safety ofthe preparation and shall not
In the texts, the term "Pharmacopoeia" or "IP" without interfere with the tests and assays prescribed for detennining
qualification means the Indian Phannacopoeia 2010 and any compliance with the official standards. Particular care should
addenda thereto. be taken to ensure that such substances are free from hannful
organisms. The freedom to the manufacturers to add auxiliary
Official and Official Articles. The word 'official' wherever
substances imposes on them the responsibility of satisfying
used in this Pharmacopoeia or with reference thereto, is
the licensing authorities on the purpose of the addition and
synonymous with 'pharmacopoeial', with 'IP' and with
the innocuity of such substances.
'compendial'. The designation IP in conjunction with the
official title on the label of an article is an indication that the Alternative Methods. The tests and assays described are the
article purports to comply with IP standards. official methods upon which the standards of the
Pharmacopoeia are based. Alternative methods of analysis
The following tenns are used where the articles for which
may be used for control purposes, provided that the methods
monographs are provided are to be distinguished.
used are shown to give results of equivalent accuracy and
An official substance is a single drug or a drug entity or a enable an unequivocal decision to be made as to whether
pharmaceutical aid for which the monograph title includes no compliance with the standards of the monographs would be
indication of the nature of a dosage fonn. achieved if the official methods were used. Automated
procedures utilising the same basic chemistry as the test
An official preparation is a drug product (dosage form) and is
procedures given in the monograph may also be used to
the finished or partially finished preparation or product ofone
determine compliance. Such alternative or automated
or more official substances fonnulated for use on the patient.
procedures must be validated.
An article is an item for which a monograph is provided,
In the event of doubt or dispute, the methods of analysis of
whether an official substance or an official preparation.
the Phannacopoeia are alone authoritative and only the result
Official Standards. The requirements stated in the obtained by the procedure given in this Phannacopoeia is
monographs apply to articles that are intended for medicinal conclusive.

1731
GENERAL NOTICES IP 2010

Meanings ofTerms per cent v/v (percentage, volume in volume) expressing


Alcohol. The term "alcohol" without qualification means the number ofmillilitres of substance in 100 millilitres of
ethanol (95 per cent). Other dilutions of ethanol are indicated final product.
by the term "ethanol" or "alcohol" followed by a statement of The expression "parts per million" refers· to the weight in
the percentage by volume of ethanol (C 2H60) required. weight, unless otherwise stated.
Desiccator. A tightly-closed container of suitable size and Where the content of a substance is expressed in terms of the
design that maintains an atmosphere oflow moisture content chemical formula for that substance an upper limit exceeding
by means of silica gel or phosphorus pentoxide or other 100 per cent may be stated. Such an upper limit applies to the
suitable desiccant. result ofthe assay calculated in terms ofthe equivalent content
ofthe specified chemical formula. For example, the statement
Drying and ignition to constant weight. Two consecutive 'contains not less than 99.0 per cent and not more than 101.0
weighings after the drying or igniting operations do not differ per cent of C 7H 60 2 implies that the result of-the assay is not
by more than 0.5 mg, the second weighing following an less than 99.0 per cent and not more than 101.0 per cent,
additional period of drying or of ignition respectively calculated in terms ofthe equivalent content of C 7H 60 2 .
appropriate to the nature and quantity of the residue.
Where the result ofan assay or test is required to be calculated
Ethanol. The term "ethanol" without qualification means with reference to the dried, anhydrous, ignited substance, or
anhydrous ethanol or absolute alcohol. the substance free from solvent, the determination of loss on
drying, water content, loss on ignition, content ofthe specified
Filtration. Unless otherwise stated, filtration is the passing of
a liquid through a suitable filter paper or equivalent device solvent, respectively is carried out by the method prescribed
in the relevant test in the m o n o g r a p h . ·
until the filtrate is clear.
Expression of Concentrations. The following expressions in
Freshly prepared. Made not more than 24 hours before it is
addition to the ones given under Expression of Content are
issued for use..
also used:
Label. Any printed packing material, including package inserts
per cent w/v (percentage, weight in volume) expressing
that provide information on the article.
the number of grams of substance in 100 millilitres of
Negligible. A quantity not exceeding 0.50 mg. product
Solution. Where the name of the solvent is not stated, per cent v/w (percentage, volume in weight) expressing
"solution" implies a solution in water. The water used complies the number of millilitres of substance in 100 grams of
with the requirements of the monograph on Purified Water. product.
The term 'distilled water' indicates Purified Water prepared by Usually, the strength of solutions of solids in liquids is
distillation. expressed as percentage weight in volume, ofliquids in liquids
Temperature. The symbol 0 used without qualification as percentage volume in volume, of solids in semi-solid bases
indicates the use of the Celsius thermometric scale. (e.g. creams) and of gases in liquids as percentage weight in
weight.
Water. Ifthe term is used without qualification it means Purified
Water of the Pharmacopoeia. The term 'distilled water' When the concentration of a solution is expressed as parts of
indicates Purified Water prepared by distillation. dissolved substance in parts of solution, it means parts by
weight (g) ofa solid in parts by volume (m!) ofthe final solution;
Water-bath. A bath of boiling water unless water at another as parts by weight (g) of a gas in parts by weight (g) of the
temperature is indicated. Other methods of heating may be final solution.
used provided the required temperature is approximately
When the concentration of a solution is expressed in molarity
maintained but not exceeded.
designated by the symbol M preceded by a number, it denotes
the number ofmoles ofthe stated solute contained in sufficient
Provisions Applicable to Monographs and Test Methods
Purified Water (unless otherwise stated) to produce 1 litre of
Expression of Contents. Where the content of a substance is solution.
defined, the expression "per cent" is used according to
Abbreviated Statements. Incomplete sentences are employed
circumstances with one of two meanings:
in parts of the monographs for directness and brevity (for
per cent w/w (percentage, weight in weight) expressing example, Iodine Value. Not more than ; Relative Density.
the number of grams of substance in 100 grams of fmal .......to ........) Where the tests are abbreviated, it is to be
product, understood that the test method referred to in brackets

1732
IP 2010 GENERAL NOTICES

provides the method to be followed and that the values Excipients. Any substance added in preparing an official
specified are the applicable limits. preparation shall be innocuous, shall have no adverse influence
in the therapeutic efficacy of the active ingredients and shall
Weights and Measures. The metric system of weights and
not interfere with the tests and assays of the Pharmacopoeia.
measures is employed in the Pharmacopoeia. All measures are
Care should be taken to ensure that such substances are free
required to be graduated at 25° and all measurements in tests
from halwful organisms.
and assays, unless otherwise stated, are to be made at that
temperature. Graduated glass apparatus used in analytical Individual Monographs
operations shall comply with the requirements stated in
Chapter 2.1.6 Drug products that are the subject ofan individual monograph
are also required to comply with the tests given in the general
monographs.
Monographs Titles. The main title for a drug substance is the International
(;eneralMonographs Non-proprietary Name (INN) approved by the World Health
Organization. Subsidiary names and synonyms have also been
General monographs on dosage fonus include requirements given in some cases; where included, they have the same
ofgeneral application and apply to all preparations within the significance as the main title.
scope of the Introduction section of the general monograph, The main titles of drug products are the ones commonly
except where a preamble limits the application. The recognised in practice. Synonyms drawn from the full non-
requirements are not necessarily comprehensive for a given proprietary name of the active ingredient or ingredients have
specific preparation; additional requirements may sometimes also been given. Where, however, a product contains one or
be given in the individual monograph for it. the other ofdifferent salts ofan active molecule, the main title
Production. Statements given under the heading Production is based on the full name ofthe active ingredient. For example,
relate to particular aspects of the mimufacturing process and Chloroquine Phosphate Tablets and Chloroquine
are not necessarily comprehensive. However, they are SulphateTablets.
mandatory instructions to manufacturers. They may relate, Chemical Formulae. When the chemical structure ofan official
for example, to source materials, to the manufacturing process substance is known or generally accepted, the graphic and
and its validation and control, to any in-process testing that molecular formulae are normally given at the beginning ofthe
is to be carried out by the manufacturer on the final product monograph for. information. This information refers to the
either on selected batches or on each batch prior to release. chemically pure substance and is not to be regarded as an
All this cannot be verified on a sample ofthe final product by indication of the purity of the official material. Elsewhere, in
an independent analyst. It is for the licensing authority to statement of purity and strength and in descriptions of
verify that the instructions have been followed. processes of assay, it will be evident from the context that the
The absence of a section on Production does not imply that formulae denote the chemically pure substances.
attention to features such as those given above is not required. Where the absolute stereochemical configuration is specified,
An article described in a monograph of the Pharmacopoeia is the International Union of Pure and Applied Chemistry
to be manufactured in accordance with the principles of good (IUPAC) RlS and E/Z systems of designation have been used.
manufacturing practice and in accordance with the If the substance is an enantiomer of unlmown absolute
requirements of the Drugs and Cosmetics Rules, 1945. The stereochemistry, the sign ofthe optical rotation, as determined
general principles applicable to the manufacture and quality in the solvent and under the conditions specified in the
assurance of drugs and preparations meant for human use monograph, has been attached to the systematic name. An
apply equally to veterinary products as well. indication ofsign ofrotation has also been given where this is
Manufacture of Drug Products. The opening definitive incorporated in a trivial name that appears on an IUPAC
statement in certain monographs for drug products is given in preferred list.
terms ofthe active ingredient(s) only. Any ingredient(s) other Atomic and Molecular Weights. The atomic weight or
than those included in the statement, must comply with the molecular weight is shown, as and when appropriate at the
general notice on Excipients and the product must conform to top right hand corner of the monograph. The atomic and
the Pharmacopoeial requirements. molecular weights and graphic formulae do not constitute .
Official preparations are prepared only from ingredients that analytical standards for the substances described.
comply with the requirements of the pharmacopoeial Definition. The opening statement of a monograph is one
monographs for those individual ingredients for which that constitutes an official definition of the substance,
monographs are provided. preparation or other article that is the subject of the

1733
GENERAL NOTICES IP 2010

monograph. In certain monographs for pharmaceutical Solubility. Statements on solubility are given in Chapter 2.4.26
preparations the statement is given in terms of the principal and are intended as infonnation on the approximate solubility
ingredient(s). at a temperature between 15° and 30°, unless otherwise stated,
In monographs on vegetable drugs, the definition indicates and are not to be considered as official requirements. However,
whether the subject of the monograph is, for example, the a test for solubility stated in a monograph constitutes part of
whole drug or the drug in powdered fonn. the standards for the substance that is the subject of that
monograph.
Certain pharmaceutical substances and other articles are
defined by reference to a particular method ofmanufacture. A Test Methods
statement that a substance or article is prepared or obtained
by a certain method constitutes part of the official definition References to general methods of testing are indicated by test
and implies that other methods are not permitted. A statement method numbers in brackets immediately after the heading of
that a substance may be prepared or obtained by a celiain the test or at the end of the text.
method, however, indicates that this is one possible method Identification. The tests given under the heading Identification
and does not imply that other methods are not permissible. are not necessarily sufficient to establish absolute proof of
Statement of content. The limits of content stated are those identity. They provide a means of verifying that the identity
detennined by the method described under Assay. of the material under examination is in accordance with the
label on the container.
Category. The statement of category is provided for
information and is indicative ofthe medical or pharmaceutical In celtain monographs alternative series ofidentification tests
basis for recognition in the Pharmacopoeia. It generally are given; compliance with either one or the other set of tests
represents an application of the best known pharmacological is adequate to verify the identity of the aIticle.
action of the article or of its active ingredient. In the case of When tests for infrared absorption are applied to material
pharmaceutical aids it may indicate the more common usage extracted fi'om fonnulated preparations, strict concordance
ofthe article. The statement is not intended to limit iIi any way with the specified reference spectrum may not always be
the choice or use of the article nor to indicate that it has no possible, but nevertheless a close resemblance between the
other activity or use. spectrum ofthe extracted material and the specified reference
Dose. Doses mentioned in the Pharmacopoeia are intended spectrum should be achieved.
merely for general guidance and represent, unless otherwise
stated, the average range of quantities which are generally Tests andAssays
regarded as suitable for adults when administered by mouth. The tests and assays are the official methods upon which the
They are not to be regarded as binding upon the prescribers. standards of the Pharmacopoeia depend. The requirements
The medical practitioner will exercise his own judgment and are not framed to take into account all possible impurities. It is
act on his own responsibility in respect of the amount of any not to be presumed, for example, that an impurity that is not
therapeutic agent he may prescribe or administer or the detectable by means of the prescribed tests is tolerated.
frequency of its administration. If it is usual to administer a Material found to contain such an impurity is not of
drug by a method other than by mouth, the single dose suitable pharmacopoeial quality ifthe nature or amount ofthe impurity
for that method of administration is mentioned. In the case of found is incompatible with good pharmaceutical practice.
some preparations notes have been given below the statement
of doses to show the approximate quantities of active Pharmacopoeial methods and limits should be used merely as
ingredients contained in the maximal doses as information for compliance requirements and not as requirements to guarantee
the prescriber. total quality assurance. Tests and assays are prescribed for
the minimum sample available on which the attributes ofthe
Usual Strength. The statement on the usual strength(s) of a
alticle should be measured. Assurance of quality must be
preparation given in the individual monograph indicates the
ensured by the manufacturer by the use of statistically valid
strength(s) usually marketed for information ofthe pharmacist
sampling and testing programmes.
and the medical practitioner. It does not imply that a strength
other than the one(s) mentioned in the individual monograph Tests. Unless otherwise stated, the assays and tests are carried
meeting all the prescribed requirements cannot be out at a temperature between 20° and 30°.
manufactured and marketed with the approval of the Where it is directed that an analytical operation is to be carried
appropriate authority. out 'in subdued light', precautions should be taken to avoid
Description. The statements under the heading Description exposure to direct sunlight or other strong light. Where a
are not to be interpreted in a strict sense and are not to be procedure is directed to be performed 'protected from light'
regarded as official requirements. precautions should be taken to exclude actinic light by the

1734
IP 2010 GENERAL NOTICES

use oflow-actinic glassware, working in a dark room or similar Unless otherwise stated, comparative tests are carried out
procedures. using identical tubes of colourless, transparent, neutral glass
with a flat base, commonly known as Nessler cylinders.
For preparations other than those of fixed strength, the
quantity to be taken for a test or an assay is usually expressed Reagents and Solutions. The reagents required for the tests
in terms of the active ingredient. This means that the quantity and assays of the Pharmacopoeia are defined in the various
ofthe active ingredient expected to be present and the quantity chapters showing their nature, degree of purity and the
of the preparation to be taken are calculated from the strength strengths of the solutions to be made from them. The
stated on the label. requirements set out are not intended to imply that the materials
are suitable for use in medicine; reagents not covered by
Other Tests. In the monographs on dosage forms and certain
monographs in the phannacopoeia shall not be claimed to be
preparations, under the sub-heading 'Other tests' it is stated
ofIP quality.
that the article complies with the tests stated under the general
monograph ofthe relevant dosage form or preparation. Details The term' analytical reagent grade of commerce' implies that
of such tests are provided in the general monographs. the chemical is ofa high degree ofpurity wherein the limits of
various impurities are known. Where it is directed to use a
Limits. The limits given are based on data obtained in normal
'general laboratory reagent grade ofcommerce' it is intended
analytical practice. They take into account nonnal analytical
that a chemically pure grade material, not necessarily required
errors, of acceptable variations in manufacture and of
to be tested for limiting or absence of certain impurities, is to
deterioration to an extent that is acceptable. No further
be used.
tolerances are to be applied to the limits for determining whether
or not the article under examination complies with the Indicators. Where the use ofan indicator solution is mentioned
requirements of the monograph. in an assay or test, approximately 0.1 ml of the solution shall
be added, unless otherwise directed.
Quantities. Unless otherwise stated, the quantities to be taken
for assays, limit tests and other tests are of the substance Reference Substances. Certain monographs require the use
under examination. of a chemical reference substance or a biological reference
preparation or a reference spectrum These are authentic
In tests with numerical limits and assays, the quantity stated
specimens chosen and verified on the basis oftheir suitability
to be taken for testing is approximate. The amount actually
for intended use as prescribed in the Pharmacopoeia and are
used, which may deviate by not more than 10 per cent from
not necessarily suitable in other circumstances.
that stated, is accurately weighed or measured and the result
ofanalysis is calculated from this exact quantity. In tests where IP Reference Substances, abbreviated to IPRS (and referred
the limit is not numerical but usually depends upon to as RS in the individual monographs) are issued by the
comparison with the behaviour of a reference in the same Indian Pharmacopoeia Commission (IPC). They are the official
conditions,. the stated quantity is taken for testing. Reagents standards to be used in cases of arbitration. Secondary
are used in the prescribed amounts. Standards (Working Standards) may be used for routine
analysis, provided they are standardized at regular intervals
Quantities are weighed or measured with an accuracy
against the Reference Substances
commensurate with the indicated degree of precision. For
weighings, the precision is plus or minus 5 units after the last Biological Reference Substances, .also abbreviated to IPRS
figure stated. For example, 0.25 g is to be interpreted as 0.245 and Standard Preparations of antibiotics are issued by
g to 0.255 g. For the measurement of volumes, if the figure agencies authorised by the IPC. They are standardized against
after the decimal point is a zero or ends in a zero, e.g. 10.0 ml or the International Standards and Reference Preparations
0.50 ml, the volume is measured using a pipette, a volumetric established by the World Health Organization (WHO). The
flask or a burette, as appropriate; in other cases, a graduated potency of these preparations is expressed in International
measuring cylinder or a graduated pipette may be used. Units. .
Volumes stated in microlitres are measured using a micropipette Reference spectra are published by the IPC and they are
or microsyringe. accompanied by information concerning the conditions used
The term 'transfer' is used generally to indicate a quantitative for sample preparation and recording of the spectra.
operation. Test Animals. Unless otherwise directed, animals used in a
Apparatus. Measuring and weighing devices and other test or an assay shall be healthy and are drawn from a unifOlID
apparatus are described in the chapter entitled'Apparatus for stock, and have not previously been treated with any material
Tests and Assays'. A specification for a definite size or type that will interfere with the test or the assay.
of container or apparatus in a test or assay is given merely as Calculation of Results. In determining compliance with a
a recommendation. numerical limit in assay or test, the result should be calculated

1735
GENERAL NOTICES IP 2010

to one decimal place more than the significant figures stated Where no specific storage directions or limitations are given
and then rounded up or down as follows: if the last figure in the monograph or by the manufacturer, it is to be understood
calculated is 5 to 9, the preceding figure is increased by 1; if it that the storage conditions include protection from moisture,
is 4 or less, the preceding figure is left unchanged. freezing and excessive heat (any temperature above 40°).
Storage. Statements under the side-heading Storage constitute Storage Containers. The requirements, guidance and
non-mandatory advice. The articles ofthe Pharmacopoeia are information on containers for pharmaceutical use are given in
to be stored under conditions that prevent contamination and, the chapter entitled Containers (6.1)
as far as possible, deterioration. Precautions that should be In general, an article should be packed in a well-closed
taken in relation to the effects of the atmosphere, moisture, container i.e. one that protects the contents from contamination
heat and light are indicated, where appropriate, in the individual by extraneous solids, liquids or vapours and from loss of the
monograph. article under normal conditions of handling and storage.
Where, additionally, loss or deterioration of the article from
Specific directions are given in some monographs with respect effervescence, deliquescence or evaporation under normal
to the temperatures at which Pharmacopoeial articies should conditions ofstorage is likely, the container must be capable
be stored, where it is considered that usage at a lower or of being tightly closed, and re-closed after use.
higher temperature may produce undesirable results. The
In certain cases, special requirements of pack have been
storage conditions are defined by the following terms:
indicated in some monographs under Storage, using
Store in a dry, well ventilated place at a temperature not expressions that have been defined in chapter 6.1.
exceeding 30°
Labelling. The labelling of drugs and pharmaceuticals is
Store in a refrigerator (20 to 8°). Do not freeze governed by the Drugs and Cosmetics Rules, 1945. The
Store in a freezer (-2° to -18°) statements that are given in the monographs under the side-
heading 'Labelling' are not comprehensive. Only those that
Store in a deep freezer (Below _18°)
are necessary to demonstrate compliance or otherwise with
Storage conditions not related to temperature are indicated in the monograph have been given and they are mandatory. For
the following terms: example, in the monograph on Betamethasone Sodium Tablets
the labelling statement is "The label states the strength in
Store protected from light
terms ofthe equivalent amount ofbetamethasone". Any other
Store protected from light and moisture statements are included as recommendations.

1736
INDIAN PHARMACOPOEIA 2010 MONOGRAPHS

DRUG SUBSTANCES, DOSAGE FORMS


AND
PHARMACEUTICAL AIDS

NtoZ .... 1739

1737
INDIAN PHARMACOPOEIA 2010 MONOGRAPHS

NalidixicAcid 1743
Nalidixic Acid Tablets 1743
Nalorphine Hydrochloride 1744
Nalorphine Injection 1745
Naloxone Hydrochloride 1745
Naloxone Injection 1747
Naltrexone Hydrochloride 1748
Naltrexone Tablets 1749
Nandrolone Decanoate 1750
Nandrolone Decanoate Injection 1751
Nandrolone Phenylpropionate 1751
Nandrolone Phenylpropionate Injection 1752
Naphazoline Nitrate 1753
Naproxen 1754
Naproxen Oral Suspension 1755
Naproxen Suppositories 1756
Naproxen Sustained-release Tablets 1757
Naproxen Tablets 1758
Nebivolol Hydrochloride 1758
Nebivolol Tablets 1759
NelfinavirMesylate 1760
Nelfinavir Mesylate Oral Powder 1761
Nelfinavir Tablets 1762
Neomycin Sulphate 1763
Neomycin Eye Drops 1764
Neomycin Eye Ointment 1765
Neostigmine Bromide 1766
Neostigmine Tablets 1767
I

Neostigmine Methylsulphate 1767


Neostigmine Injection 1768

1739
MONOGRAPHS INDIAN PHARMACOPOEIA 2010

Neotame 1769
Nevirapine 1770
Nevirapine Oral Suspension 1771
Nevirapine Tablets 1772
Niclosamide 1773
Niclosamide Tablets 1774
Nicotinamide 1775
Nicotinamide Tablets 1776
NicotinicAcid 1776
Nicotinic Acid Tablets 1777
Nicoumalone 1777
Nicoumalone Tablets 1778
Nifedipine 1779
Nifedipine Capsules 1780
Nifedipine Sustained-release Tablets 1781
Nifedipine Tablets 1782
Nikethamide 1783
Nikethamide Injection 1784
Nitrazepam 1784
Nitrazepam Tablets 1785
Nitrofurantoin 1786
Nitrofurantoin Tablets 1787
Nitrofurazone 1787
Nitrous Oxide 1788
Noradrenaline Bitartrate 1789
Noradrenaline Bitartrate Injection 1790
Norethisterone 1791
Norethisterone Tablets 1792
Norfloxacin 1793
Norfloxacin Eye Drops 1794
Norfloxacin Tablets 1794
Norgestrel 1795
Norgestrel and Ethinyloestradiol Tablets 1796

1740
INDIAN PHARMACOPOEIA 2010 MONOGRAPHS

Nortriptyline Hydrochloride 1797


Nortriptyline Tablets 1797
Noscapine 1798
Noscapine Linctus 1800
Novobiocin Sodium 1800
Nystatin 1801
Nystatin Ointment 1802
Nystatin Pessaries 1803
Nystatin Tablets 1803

1741
IP 2010 NALIDIXIC ACID TABLETS

Nalidixic Acid Reference solution (a). A 0.002 per cent w/v solution of the
substance under examination in dichloromethane.
Reference solution (b). A 0.0008 per cent w/v solution of the
substance under examination in dichloromethane.
Reference solution (c). A 0.1 per cent w/v solution of nalidixic
acid RS in dichloromethane.
Apply to the plate 10 III ofeach solution. After development,
dry the plate in air and examine in ultraviolet light at 254 nm.
Any secondary spot in the chromatogram obtained with test
Mol. Wt. 232.2 solution (a) is not more intense than the spot in the
chromatogram obtained with reference solution (a) and not
Nalidixic Acid is l-ethyl-l ,4-dihydro-7-methyl-4-oxo-l ,8-
more than one such spot is more intense than the spot in the
naphthyridine-3-carboxylic acid.
chromatogram obtained with reference solution (b).
Nalidixic Acid contains not less than 99.0 per cent and not
Heavy metals (2.3.13).1.0 g complies with the limit test for
more than 101.0 per cent of ClzHI2Nz03, calculated on the
heavy metals, Method B (20 ppm).
dried basis.
Sulphated ash (2.3.18) Not more than 0.1 per cent.
Category. Antibacterial.
Loss on drying (2.4.19). Not more than 0.5 per cent, determined
Dose. 2 to 4 g daily, in divided doses.
on 1.0 g by drying in an oven at 105 0 •
Description. A white to slightly yellow, crystalline powder.
Assay. Weigh accurately about 0.15 g, dissolve in 10 ml of
Identification dichloromethane, add 30 ml of 2-propanol and 10 mlof carbon
dioxide-free water and titrate with 0.1 M ethanolic sodium
Test A may be omitted iftests B, C andD are carried out. Tests hydroxide, determining the end-point potentiometrically
B, C and D may be omitted if test A is carried out. (2.4.25) and using a glass electrode as the indicator electrode
A. Determine by infrared absorption spectrophotometry (2.4.6). and a silver-silver chloride reference electrode with a sleeve
Compare the spectrum with that obtained with nalidixic acid diaphragm or a capillary tip filled with a saturated solution of
RS or with the reference spectrum ofnalidixic acid. lithium chloride in ethanol. Throughout the titration keep
the temperature ofthe solution at 15 0 to 20 0 and pass a current
B. When examined in the range 230 nm to 360 nm (2.4.7), a of nitrogen through the solution.
0.0005 per cent w/v solution in 0.1 M sodium hydroxide shows
absorption maxima at about 258 nm and 334 nm; ratio of the 1 ml of 0.1 M ethanolic sodium hydroxide is equivalent to
absorbance at about 258 nm to that at about 334 nm, 2.2 to 2.4. 0.02322 g ofClzHlzNz03.
C. In the test for Related substances, the principal spot in the Storage. Store protected from light and moisture.
chromatogram obtained with test solution (b) corresponds to
that in the chromatogram obtained with reference solution (c).
D. Dissolve 0.1 gin 2 ml of hydrochloric acid and add 0.5 ml Nalidixic Acid Tablets
of a 10 per cent w/v solution of 2-naphthol in ethanol (95 per
cent); an orange-red colour develops.
Nalidixic Acid Tablets contain not less than 95.0 per cent and
not more than 105.0 per cent ofthe stated amount ofnalidixic
Tests acid, ClzHlzNz03.

Related substances. Determine by thin-layer chromatography Usual strengths. 250 mg; 500 mg.
(2.4.17), coating the plate with silica gel HF254. ' Identification
Mobile phase. A mixture of 70 volumes of ethanol (95 per
To a quantity ofthe powdered tablets containing 1g ofNalidixic
cent), 20 volumes of dichloromethane and 10 volumes of5 M
Acid add 50 ml of chloroform, shake for 15 minutes, filter and
ammonia.
evaporate the filtrate to dryness. The residue, after drying at
Test solution (a). Dissolve 0.2 g of the substance under 105 0 , complies with the following tests.
examination in 10 ml of dichloromethane.
A. Determine by infrared absorption spectrophotometry (2.4.6).
Test solution (b). A 0.1 per cent w/v solution of the substance Compare the spectrum with that obtained with nalidixic acid
under examination in dichloromethane. RS or with the reference spectrum ofnalidixic acid.

1743
NALIDIXIC ACID TABLETS IP 2010

B. When examined in the range 230 nm to 360 nm (2.4.7), a Nalorphine Hydrochloride contains not less than 97.0 per cent
0.0005 per cent w/v solution in 0.1 M sodium hydroxide shows and not more than 103.0 per cent ofCI9HzIN03,HCl, calculated
absorption maxima at about 258 nm and 334 nm; ratio of the on the dried basis.
absorbance at about 258 nm to that at about 334 nm, 2.2 to 2.4.
Category. Narcotic antagonist.
Tests Dose. By intravenous injection, 5 mg, repeated twice at three
Related substances. Determine by thin-layer chromatography minute intervals, if necessary.
(2.4.17), coating the plate with silica gel HF254. Description. A white or almost white, crystalline powder;
Mobile phase. A mixture of 70 volumes of ethanol (95 per odourless. It slowly darkens on exposure to air and light.
cent), 20 volumes of dichloromethane and 10 volumes of
5 Mammonia.
Identification
Test solution. Shake a quantity of the powdered tablets Test A may be omitted if tests B, C, D and E are carried out.
containing 0.1 g ofNalidixic Acid with 50 ml of chloroform for Tests C and D may be omitted if tests A, Band E are carried
15 minutes, filter, evaporate the filtrate to dryness and dissolve out.
the residue in 5 ml of chloroform. A. Determine by infrared absorption spectrophotometry (2.4.6).
Reference solution. Dilute 1 volume of the test solution to Compare the spectrum with that obtained with nalorphine
200 volumes with chloroform. hydrochloride RS.
Apply to the plate 10 III of each solution. After development, B. When examined in the range 230 nm to 360 nm (2.4.7), a
dry the plate in air and examine in ultraviolet light at 254 nm. 0.01 per cent w/v solution in 0.1 M sodium hydroxide shows
Any secondary spot in the chromatogram obtained with the an absorption maximum only at about 298 nm; absorbance at
test solution is not more intense than the spot in the about 298 nm, about 0.6.
chromatogram obtained with the reference solution.
C. To 10 ml of a 2 per cent w/v solution add 0.05 ml of dilute
Other tests. Complies with the tests stated under Tablets. ammonia solution; a white precipitate soluble in sodium
Assay. Weigh and powder 20 tablets. Weigh accurately a hydroxide solution is produced.
quantity of the powder containing about 0.1 g of Nalidixic D. Dissolve 2 mg in 2 ml of water, add 0.15 ml ofpotassium
Acid, add 150 ml of 0.1 M sodium hydroxide, shake for 3 fen-icyanide solution containing, in each ml, 0.05 mlofferric
minutes, dilute to 200.0 ml with 0.1 M sodium hydroxide, mix chloride solution; a deep bluish green colour is produced
and allow to stand for 15 minutes. Dilute 2.0 ml ofthe solution immediately.
to 100.0 ml with water and measure the absorbance of the
resulting solution at the maximum at about 334 nm (2.4.7), E. Gives reaction A ofchlorides (2.3.1).
using 0.1 M sodium hydroxide as the blank Calculate the
content of C 12H 12N z0 3 taking 494 as the specific absorbance Tests
at 334 nm. Melting range (2.4.21). 260 0 to 263 0 •
Storage. Store protected from light and moisture. Acidity. Dissolve 0.2 g in 10 ml offreshly boiled and cooled
water and titrate with O. 02 M sodium hydroxide using methyl
red solution as indicator; not more than 0.2 ml of 0.02 M
Nalorphine Hydrochloride sodium hydroxide is required to change the colour of the
solution.
Specific optical rotation (2.4.22). -122 0 to -125 0 , determined
in a 2.0 per cent w/v solution.
Sulphated ash (2.3.18). Not more than 0.1 percent.
Loss on drying (2.4.19). Not more than 0.5 per cent, determined
on 1.0 g by drying in an oven at 1000 at a pressure not exceeding
0.7 kPa for 2 hours.
Assay. Weigh accurately about 25 mg and dissolve in sufficient
CI9HzIN03,HCl Mol. Wt. 347.8
water to produce 250 ml. Measure the absorbance of the
Nalorphine Hydrochloride is 17-allyl-7,8-didehydro-4,5a- resulting solution at the maximum at about 285 nm (2.4.7).
epoxymorphinan-3,6a-diol hydrochloride. Calculate the content ofCI9HzIN03,HCl from the absorbance

1744
IP 2010 NALOXONE HYDROCHLORIDE

obtained by repeating the operation with nalorphine by repeating the operation with nalorphine hydrochloride
hydrochloride RS in place of the substance under RS.
examination.
Storage. Store protected from light.
Storage. Store protected from light and moisture.

Naloxone Hydrochloride
Nalorphine Injection
Naloxone Hydrochloride Dihydrate
Nalorphine Hydrochloride Injection
Nalorphine Injection is a sterile solution of Nalorphine HO
Hydrochloride in Water for Injections containing suitable
buffering agents.
Nalorphine Injection contains not less than 90.0 per cent and N~CH2
not more than 110.0 per cent ofthe stated amount ofnalorphine 1Ilo...00..-'"

,-'
hydrochloride, CI9H21N03,HCl.
Usual strength. 10 mg per ml.
o
CI9H2IN04,HCI,2H20 Mol. Wt. 399.9
Identification Naloxone Hydrochloride is 17-allyl-4,5-a-epoxy-3,14-
dihydroxymorphinan-3-one hydrochloride dihydrate.
A. To a volume containing 50 mg ofNalorphine Hydrochloride
add dilute ammonia solution until the solution is alkaline and Naloxone Hydrochloride contains not less than 98.0 per cent
extract with 25 ml ofa mixture of 1 volume of ethanol (95 per and not more than 102.0 per cent of C19H22ClN04, calculated
cent) and 3 volumes of chloroform and evaporate the extract on the anhydrous basis.
to dryness. Dry the residue at a pressure not exceeding 2 kPa.
Category. Antidote for opioids poisoning.
The residue complies with the following test.
Description. A white to almost white, hygro$copic, crystalline
Determine by infrared absorption spectrophotometry (2.4.6).
powder.
Compare the spectrum with that obtained with nalorphine
hydrochloride RS. Identification
B. To a volume containing 0.1 g ofNalorphine Hydrochloride
Test A may be omitted if tests Band C are carried out. Test B
add 0.05 ml of dilute ammonia solution; a white precipitate
may be omitted if tests A and C are carried out.
soluble in sodium hydroxide solution is produced.
A. Determine by infrared absorption spectrophotometry
C. Gives reaction A ofchlorides (2.3.1).
(2.4.6).Compare the spectruin with that obtained with naloxone
Tests hydrochloride dihydrate RS or with the reference spectrum
of naloxone hydrochloride.
pH (2.4.24).6.0 to 7.5.
B. Detennine by thin-layer chromatography (2.4.17), coating
Other tests. Complies with the tests stated under Parenteral the plate with silica gel G
Preparations (Injections). Mobile phase. Mix 5 volumes of methanol and 95 volumes of
Assay. Transfer an accurately measured volume containing the upper layer from a mixture of60 ml of ammonia and 100 m1
about 10 mg of Nalorphine Hydrochloride to a separating of butan-I-ol.
funnel, add 1 ml of dilute hydrochloric acid and dilute to Test solution. Dissolve 8 mg of the substance under
10 ml with water. Extract with five successive quantities, each examination in 0.5 ml of water and dilute to 1 m1 with methanol.
of 5 ml, of chloroform, allowing the layers to separate before
drawing offeach cWoroform extract and discard the chloroform Reference solution. Dissolve 8 mg of naloxone hydrochloride
extracts. Transfer the aqueous layer to a 100-ml volumetric dihydrate RS in 0.5 ml of water and dilute to 1 ml with methanol.
flask with the aid of small quantities of water and dilute to Apply to the plate 5 I.d of each solution, Allow the mobile
volume with water. Measure'the absorbance of the resulting phase to rise 8 cm. Dry the plate in air and spray with a freshly
solution at the maximum at about 285 nm (2.4.7). Calculate prepared 0.5 per cent w/v solution ofpotassium ferricyanide
the content of C19H21N03,HCI from the absorbance obtained in ferric chloride solution and examine in daylight. The

1745
NALOXONE HYDROCHLORIDE IP 2010

principal spot in the chromatogram obtained with the test to pH 2.0 with a 50 per cent v/v solution of
solution corresponds to that in the chromatogram obtained orthophosphoric acid,
with the reference solution. - flow rate. 1.5 ml per minute,
- a linear gradient programme using the conditions given
C. Gives reaction A ofchlorides (2.3.1).
_below,
spectrophotometer set at 230 urn,
Tests
- injection volume. 20 /-ll.
Appearance ofsolution. A2.0 per cent w/v solution in carbon Time Mobile phase A Mobile phase B
dioxide-free water (Solution A) is clear (2.4.1) and colourless (in min.) (per cent v/v) (per cent v/v)
(2.4.1).
0~40 100~0 0~100
Acidity or alkalinity. To 10 ml of solution A add 0.05 ml of 40~50 0 100
methyl red solution. Not more than 0.2 ml of 0.02 M sodium
Inject reference solution (a). Adjust the sensitivity of the
hydroxide or 0.02 M hydrochloric acid is required to change
system so that the peak-to-valley ratio is minimum 2.0, where
the colour of the indicator.
Hp is height above the baseline of the peak due to impurity D
Specific optical rotation (2.4.22). -170° to -181°, detennined and H v is the height above the baseline of the lowest point of
in solution A. the curve separating this peak from the peak due to naloxone.
Related substances. Determine by liquid chromatography The relative retention time with reference to naloxone, for
(2.4.14). impurity C, impurity A, impurity F, impurity D, impurity E and
Test solution. Dissolve 0.125 g of the substance under impurity B is about 0.6 minute, 0.8 minute, 0.9 minute, 1.1
examination in 25 m1 of 0.1 M hydrochloric acid. minutes, 3.0 minutes and 3.2 minutes respectively.

Reference solution (a). Dissolve 5 mg of naloxone for peak Inject reference solution (b) and the test solution. In the
identification RS (containing naloxone impurity A (4,5cx -epoxy- chromatogram obtained with the test solution, the area of
3, 14-dihydroxymorphinan-6-one) (noroxymorphone), each secondary peak corresponding to naloxone impurities
naloxone impurity B (4,5cx-epoxy-14-hydroxy-17-(prop-2-enyl)- A, B, C, E, F is not more than the area ofthe principal peak in
3-(prop-2-enyloxy)morphinan-6-one) (3-0-allylnaloxone), the chromatogram obtained with reference solution (b) (0.2
naloxone impurity C (4,5cx -epoxy-3,1Oli,14-trihydroxy-17-(prop- per cent). The area of secondary peak corresponding to
2-enyl)morphinan-6-one) (1 Ocx -hydroxynaloxone), naloxone naloxone impurity D is not more than 1.5 times the area ofthe
impurity D (7,8-didehydro-4,5cx -epoxy-3,14-dihydroxy-17- principal peak in the chromatogram obtained with reference
(prop-2-enyl)morphinan-6-one) (7 ,8-didehydronaloxone), solution (b) (0.3 per cent).The area' of any other impurities is
naloxone impurity E (4,5 cx:4',5' cx-diepoxy-3,3',14,14'- not more than 0.5 times the area of the principal peak in the
tetrahydroxy-17,IT-bis(prop-2-enyl)-2,2'-bimorphinanyl-6,6'- chromatogram obtained with reference solution (b) (0.1 per
dione) (2,2'-bisnaloxone) and naloxone impurity F (4,5cx- cent). The sum ofthe areas of all other secondary peaks is not
epoxy-3,1013,14-trihydroxy-17- (prop-2-enyl)morphinan-6-one) more than 4 times the area of the principal peak in the
(lOcx-hydroxynaloxone) in 1 m1 of 0.1 M hydrochloric acid. chromatogram obtained with reference solution (b) (0.8 per
cent). Ignore any peak with an area less than 0.25 times the
Reference solution (b). Dilute 1.0 m1 ofthe test solution to 20 area of the principal peak in the chromatogram obtained with
m1 with 0.1 Mhydrochloric acid. Dilute 1.0 ml ofthis solution the reference solution (b) (0.05 per cent).
to 25.0 ml with 0.1 M hydrochloric acid.
Water (2.3.43). 7.5 per cent to 11.0 per cent, determined on
Chromatographic system O.2g.
- a stainless steel column 12.5 cm x 4 mm, packed with
octylsilane bonded to porous silica (5 /-lm), Sulphated ash (2.3.18). Not more than 0.2 per cent, determined
- column temperature. 40°, on 0.5 g.
- mobile phase: A. a mixture of20 volumes of acetonitrile, Assay. Weigh accurately about 0.3 g, dissolve in 50 ml of
40 volumes of tetrahydrofuran and 940 volumes of the ethanol (95 per cent) and add 5.0 ml of O. 01 M hydrochloric
solution prepared by dissolving 1.1 g of sodium acid. Titrate with 0.1 M ethanolic sodium hydroxide,
octanesulphonate in 1000 ml of water. Adjust to pH 2.0 determining the end-point potentiometrically (2.4.25). Carry
with a 50 per cent v/v solution of orthophosphoric acid, out a blank titration.
B. a mixture of 40 volumes of
1 ml of 0.1 M ethanolic sodium hydroxide is equivalent to
tetrahydrofuran , 170 volumes of acetonitrile and 790
0.03638 g ofC19H22ClN04.
volumes of the solution prepared by dissolving 1.1 g of
sodium octanesulphonate in 1000 ml of wate/: Adjust Storage. Store protected from light.

1746
IP 2010 NALOXONE INJECTION

Naloxone Injection the combined extracts over anhydrous sodium sulphate, filter,
evaporate the filtrate to dryness and dissolve the residue in 1
Naloxone Injection is a sterile solution of Naloxone ml of methanol.
Hydrochloride in Water for Injections.
Reference solution. Dilute 1 ml of the test solution to 200 ml
Naloxone Injection contains not less than 95.0 per cent and with methanol.
not more than 105.0 per cent ofthe stated amount ofnaloxone
hydrochloride, CI9H2IN04,HCI. Apply to the plate 20 Jll of each solution. Allow the mobile
phase to rise 10 cm, protecting the plate from light. After
Usual strength. 400 Jlg per ml. development, dry the plate in a cunent of air, spray with a
freshly prepared 0.5 per cent w/v solution of potassium
Identification
hexacyanoferrate(III) in iron(IIl) chloride solution and
A. In the Assay, the principal peak in the chromatogram examine in daylight. Any secondary spot in the chromatogram
obtained with the test solution conesponds to the peak in the obtained with the test solution is not more intense than the
chromatogram obtained with the reference solution. spot in the chromatogram obtained with the reference solution
(0.5 per cent). Ignore any spot remaining on the line of
B. Detennine by thin-layer chromatography (2.4.17), coating
application.
the plate with silica gel G
Bacterial endotoxins (2.2.3). Not more than 70 ill perml ofthe
Mobile phase. A mixture of 5 volumes of methanol and 95
injection, diluted ifnecessary, with water BETto give a solution
volumes ofthe upper layer from a mixture of60 ml ofMammonia
containing 0.04 per cent w/v of anhydrous Naloxone
and 100 ml of butan-I-ol.
Hydrochloride.
Test solution. Add 1 mlofammoniabufferpH 1O.0toavolume
Other tests. Complies with the tests stated under Parenteral
ofthe injection containing the equivalent of2 mg ofanhydrous
Preparations (Injections).
naloxone hydrochloride, extract with three 20 ml quantities of
a mixture of 1 volume of propan-2-o1 and 3 volumes of Assay. Detennine by liquid chromatography (2.4.14).
chloroform, illy the combined extracts over anhydrous sodium
Solvent mixture. 0.1 volume of orthophosphoric acid, 45
sulphate, filter, evaporate the filtrate to illyness and dissolve
volumes of methanol and 55 volumes of water.
the residue in 1 ml of methanol. Dilute 1 ml ofthis solution to
20 ml with methanol. Test solution. Dilute the injection' equivalent to 0.001 per cent
w/v ofNaloxone Hydrochloride with the solvent mixture.
Reference solution. A 0.01 per cent w/v solution of naloxone
hydrochloride RS in methanol. Reference solution (a). A 0.001 per cent w/v solution of
naloxone hydrochloride RS in the solvent mixture.
Apply to the plate 20 Jll of each solution. Allow the mobile
phase to rise 10 cm, protecting the plate from light. After Reference solution (b). A 0.001 per cent w/v solution of
development, illy the plate in a cunent of air, spray with a naloxone hydrochloride RS and 0.0005 per cent w/v solution
freshly prepared 0.5 per cent w/v solution of potassium of noroxymorphone in the solvent mixture.
hexacyanoferrate (Ill) in iron(III) chloride solution and
Chromatographic system
examine in daylight. The principal spot in the chromatogram
- a stainless steel column 25 cm x 4.6 mm, packed with
obtained with the test solution corresponds to that in the
end-capped octadecylsilane bonded to porous silica (5
chromatogram obtained with the reference solution.
to 10 Jlm)(such as Zorbax C18, 7 to 8 Jlm),
Tests mobile phase: a solution containing 0.068 per cent w/v
of sodium octanesulphonate and 0.1 per cent w/v of
pH (2.4.24).3.0 to 4.5. sodium chloride in the solvent mixture,
Related substances. Detennine by thin-layer chromatography - flow rate. 1 ml per minute,
(2.4.17), coating the plate with silica gel G - spectrophotometer set at 229 nm,
- injection volume. 20 Jll.
Mobile phase. A mixture of 5 volumes of methanol and 95
volumes of the upper layer from a mixture of 60 ml of 2 M Inject reference solution (b). The test is not valid unless the
ammonia and 100 ml of butan-I-of. resolution between the peaks due to naloxone and
noroxymorphone in the chromatogram obtained with reference
Test solution. Transfer a volume of the injection containing solution (b) is not less than 1.3.
about 2 mg of Naloxone Hydrochloride in 1 ml of ammonia
bufferpH I 0.0, extract with three 20 ml quantities ofa mixture Injection reference solution (a) and the test solution.
of 1 volume ofpropan-2-o1 and 3 volumes of chloroform, dry Calculate the content ofCI9H2IN04,HCl in the injection.

1747
NALTREXONE HYDROCHLORIDE IP 2010

Storage. Store protected from light. Specific optical rotation (2.4.22). - 187° to - 195°, determined
in a 2.0 per cent w/v solution in water.
Labelling. The label states the quantity ofactive ingredient in
terms of the equivalent amount of anhydrous naloxone Related substances. Determine by liquid chromatography
hydrochloride.When naloxone is prescribed for neonatal use, (2.4.14).
Neonatal Naloxone Injection (containing the equivalent of20 Test solution. Dissolve 20 mg of the substance under
micrograms per ml ofanhydrous naloxone hydrochloride) shall examination in 10 ml of 0.1 M hydrochloric acid.
be dispensed.
Reference solution (a). Dissolve 5 mg of 17-but-3-enyl-4,5 a-
epoxy-3,14-dihydroxymorphinan-6-one RS (naltrexone
impurity C RS) in 2.5 ml of 0.1 M hydrochloric acid.
Naltrexone Hydrochloride Reference solution (b). Dilute 1.0 ml of the test solution and
1.0 ml of reference solution (a) to 100 ml with 0.1 M
hydrochloric acid. Dilute 1.0 ml ofthis solution to 10 ml with
0.1 M hydrochloric acid.
Chromatographic system
, Hel - a stainless steel column 15 cm x 4.6 mm, packed with
.........._N~ octadecylsilane bonded to porous silica (5 Ilm),
- column temperature. 40°,
- mobile phase: A. a 0.11 per cent w/v solution ofsodium
octanesulphonate, adjust the pH to 2.3 with
Mol. Wt. 377.9 orthophosphoric acid,
Naltrexone Hydrochloride is 17-(cyclopropylmethyl)-4,5a- B. acetonitrile,
epoxy-3, 14-dihydroxymorphinan-6-one hydrochloride. - a linear gradient programme using the conditions given
below,
Naltrexone Hydrochloride contains not less than 98.0 per cent - flow rate. 1.2 ml per minute,
and not more than 102.0 per cent of CzoHz4ClN04, calculated - spectrophotometer set at 230 nm,
on the anhydrous and ethanol free basis. injection volume. 10 Ill.
Category. Antidote for opioids poisoning. Time Mobile phase A Mobile phase B
Description. A white or almost white powder, very (in min.) (per cent v/v) (per cent v/v)
hygroscopic. 0-45 9H55 1~5

45-47 55~90 45~10


Identification
47-55 ~ 10
A. Dissolve 20 mg ofthe substance under examination in 5 ml Inject reference solution (b). The test is not valid unless the
of water and make allmline with dilute ammonia. Shake with resolution between the peaks due to naltrexone and naltrexone
10 ml of dichloromethane, separate the organic layer and impurity C is not less than 2.0. The relative retention time with
evaporate the solvent. On the residue, determine by infrared reference to naltrexone for 17-formyl-4,5a-epoxy-3,14-
absorption spectrophotometry (2.4.6). Compare the spectrum dihydroxymorphinan-6-one (naltrexone impurity A) is about
with that obtained with naltrexone hydrochloride RS or with 0.4, for 4,5a-epoxy-3,14-dihydroxymorphinan-6-one
the reference spectrum of naltrexone hydrochloride. (noroxymorphone) (naltrexone impurity B) is about 0.7, For
B. Gives reaction A ofchlorides (2.3.1). 17-(cyclopropylmethyl)-4,5a-epoxy-3, lOa, 14-
trihydroxymorphinan-6-one (naltrexone impurity F) is about
Tests 0.8, for 17-(cyclopropylmethyl)-4,5a-epoxy-3,10~,14-
trihydroxymorphinan-6-one (naltrexone impurity G) is about
Appearance of solution. A2.0 per cent w/v solution in carbon-
0.9, for 17-but-3-enyl-4,5a-epoxy-3,14-dihydroxymorphinan-
dioxide free water is clear (2.4.1) and not more intensely
6-one (naltrexone impurity C) is about 1.05,for l7-butyl-4,5a-
coloured than reference solution YS5 or BS5 (2.4.1).
epoxy-3,14-dihydroxymorphinan-6-one (naltrexone impurity H)
Acidity or alkalinity. To 10 ml of2.0 per cent w/v solution in is about 1.1, for 17-(cyclopropylmethyl)-4,5a-:epoxy-3,14-
carbon-dioxidefree water, add 0.05 ml of methyl redsolution. dihydroxymorphinan-6,1O-dione (naltrexone impurity I) is
Not more than 0.2 ml of 0.02 M sodium hydroxide or 0.02. M about 1.2, for 7-(cyclopropylmethyl)-4,5a-epoxy-14-hydroxy-
hydrochloric acid is required to change the colour of the 3-methoxymorphinan-6-one (naltrexone impurity 1) is about
indicator. 1.3, for 17,17'-bis(cyclopropylmethyl)-4,5a:4',5'-a-diepoxy-

1748
IP 2010 NALTREXONE TABLETS

3,3' ,14,14' -tetrahydroxy-2,2' -bimorphinanyl-6,6' -dione Usual strength. 50 mg.


(pseudonaltrexone) (naltrexone impurity D) is about 1.4, for3-
(cyclopropylmethoxy)-17-(cyclopropylmethyl)-4,5(X-epoxy~ 14- Identification
hydroxymorphinan-6-one (naltrexone impurity E) is about 1.7.
In the Assay, the principal peak in the chromatogram obtained
Inject reference solution (b) and the test solution. In the with the test solution corresponds to the peak in the
chromatogram obtained with the test solution the area any chromatogram obtained with the reference solution.
peak corresponding to naltrexone impurity C, D, E, F and G is
not more than twice the area of the principal peak in the Tests
chromatogram obtained with reference solution (b) (0.2 per
cent); the area ofany peak corresponding to naltrexone impurity Dissolution (2.5.2).
A, B, H, I and J is not more than the area ofthe principal peak Apparatus No.1,
in the chromatogram obtainedwith reference solution (b) (0.1 Medium. 900 ml of water,
per cent); the area of any other secondary peak is not more Speed and time. 50 rpm and 60 minutes.
than the area of the principal peak in the chromatogram
obtained with reference solution (b)(0.1 per cent). The sum of Withdraw a suitable volume of the medium and fllter.
the areas of all secondary peaks is not more than 10 times the Detennine by liquid chromatography (2.4.14).
area ofthe principal peak in the chromatogram obtained with
reference solution (b) (l.0 per cent). Ignore any peak with an Test solution. Use the flltrate.
area less than 0.5 times the area of the principal peak in the Reference solution. A solution of naltrexone hydrochloride
chromatogram obtained with reference solution (b) (0.05 per RS in water to obtain the same concentration as given in the
cent). test solution.
Ethanol (2.3.45). Not more than 3.0 per cent v/v, determined by Chromatographic system
Method I using the following solutions. - a stainless steel column 15 cm x 3.9 mm, packed with
Test solution. Dissolve 0.25 g of the substance under octadecylsilane bonded to porous silica (5 Ilm),
examination in 10 ml of wate/: - column temperature. 45°,
- mobile phase: a mixture of600 volumes of0.05 M buffer
Reference solution. Dilute 0.75 g of anhydrous ethanol to solution prepared by dissolving 7 g of monobasic
1000 ml with water. sodium phosphate in 1000 ml of water, add 1.1 g of
Sulphated ash (2.3.18). Not more than 0.1 per cent. . sodium 1-octane sulphonate monohydrate and 400 ml
of methanol, adjust the pH to 6.7 with dilute sodium
Water (2.3.43). Not more than 10.0 per cent, determined on
hydroxide,
O.2g.
- flow rate. 1 ml per minute,
Assay. Weigh accurately about 0.2 g of the substance under - spectrophotometer set at 280 nm,
examination, dissolve in 60 ml of ethanol (95 per cent) and ~ injection volume. 100 Ill.
add 1.0 ml of 0.1 M hydrochloric acid. Titrate with 0.1 M
Inject the reference solution. The test is not valid unless the
sodium hydroxide, determining the end-point
relative standard deviation for replicate injections is not more
potentiometrically (2.4.25). The curve shows 3 points of
than 2.0.
inflexion. Read the volume added between the flrst 2 points of
inflexion. Inject the reference solution and the test solution.
1 ml of 0.1 M sodium hydroxide is equivalent to 0.03779 g of Calculate the content of CzoHz3N04.HCl in the tablets.
CzOHZ4ClN04.
D. Not less than 80 per cent of the stated amount of
Storage. Store protected from light and moisture. CzOHZ3N04.HCl.
Uniformity of content.-Comply with the test stated under
Tablets.
Naltrexone Tablets Determine by liquid chromatography (2.4.14), as described
under Assay, using the following solution as the test solution.
Naltrexone Hydrochloride Tablets
Test solution. Disperse 1 tablet in 100 ml of 0.1 M
Naltrexone Tablets contain not less than 90.0 per cent and not
orthophosphoric acid.
more than 110.0 per cent of the stated amount ofnaltrexone
hydrochloride, C ZO H23N04.HCl. Calculate the content ofCzoHz3N04.HCl in the tablets.

1749
NALTREXONE TABLETS IP 2010

Other tests. Comply with the tests stated under Tablets. Nandrolone Decanoate
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Weigh and powder 20 tablets. Shake a quantity
o
of powdered tablets containing about 250 mg ofNaltrexone H3 C O)lCH 2 (CH 2 hCH 3
with 80 ml of 0.1 M orthophosphoric acid, sonicate for 30
minutes and dilute to 100 ml with the same solvent, filter.
Reference solution (a). Dissolve 22.5 mg of naltrexone RS in
1.5 ml of methanol and 0.6 ml of 0.1 M hydrochloric acid.
Dilute to 10 ml with 0.1 M orthophosphoric acid. o
Reference solution (b). Dissolve about 3 mg of N-(3-butenyl)- CZ8~03 Mol. Wt. 428.7
noroxymorphone hydrochloride RS (naltrexone impurity A
Nandrolone Decanoate is 3-oxo-4-estren-1713-yl decanoate.
RS) in 3.0 ml of methanol and dilute to 10 ml with 0.1 M
orthophosphoric acid. To 0.5 ml ofthis solution, add 5.0 ml of Nandrolone Decanoate contains not less than 97.0 per cent
reference solution (a) and dilute to 10 ml with 0.1 M and not more than 103.0 per cent of CZ8H4403, calculated on
orthophosphoric acid. the dried basis.
Chromatographic system Category. Anabolic steroid.
- a stainless steel column 15 cm x 3.9 mm packed with Dose. By intramuscular injection, 25 to 50 mg, every 3 weeks.
octadecylsilane bonded to porous silica (5 ).1m),
column temperature. 45°, Description. A white to creamy-offwhite, crystalline powder;
mobile phase: A. dissolve about 1.08 g of sodium 1- odour, faint and characteristic.
octanesulphonate and 23.8 g of sodium acetate in 800 Identification
ml of water. Add 1.0 ml of triethylamine and 200 mlof
methanol, adjust the pH to 6.5 with glacial acetic acid, A. Determine by infrared absorption spectrophotometry (2.4.6).
B. dissolve about 1.08 g sodium 1- Compare the spectrum with that obtained with nandrolone
octanesulphonate and 23.8 g sodium acetate in 400 ml decanoate RS or with the reference spectrum of nandrolone
of water. Add 1.0 ml of triethylamine and 600 ml of decanoate.
methanol, adjust the pH to 6.5 with glacial acetic acid, B. When examined in the range 230 nm to 360 nm (2.4.7), a
a linear gradient programme using the conditions given 0.001 per cent w/v solution in ethanol (95 per cent) shows an
below, absorption maximum only at about 239 nm; absorbance at
flow rate. 1 ml per minute, about 239 nm, about 0.41.
spectrophotometer set at 280 nm,
injection volume. 20 ).11. C. Dissolve 25 mg in 1 ml of methanol, add 2 ml of
semicarbazide acetate solution, heat under a reflux condenser
Time Mobile phase A Mobile phase B
for 30 minutes and cool; the precipitate, after recrystallisation
(min.) (per cent v/v) (per cent v/v)
from ethanol (95 per cent), melts at about 175° (2.4.21).
o 100 o
Tests
1-35 100-70 0-7100
35-36 0-7100 100-70 Specific optical rotation (2.4.22). +32.0 ° to +36.0°, determined
in a 2.0 per cent w/v solution in dioxan.
Inject reference solution (b). The test is not valid unless the
resolution between the peaks due to naltrexone and naltrexone Related substances. Determine by thin-layer chromatography
impurity A is not less than 2.0, the tailing factor is not more (2.4.17), coating the plate with silica gel GF254.
than 1.4, and the relative standard deviation for replicate Mobile phase. A mixture of 70 volumes of heptane and
injections is not more than 2.0 per cent. The relative retention 30 volumes of acetone.
time with reference to naltrexone for noroxymorphone is about Test solution. Dissolve 0.1 g of the substance under
0.55, for 10-hydroxynaltrexone is about 0.7, for naltrexone examination in 10 ml of chloroform.
impurity A is about 1.26, for 2,2a-bisnaltrexone is about 1.80
and for 10-ketonaltrexoneis about 1.99. Reference solution (a). A 0.005 per cent w/v solution of the
substance under examination in chloroform.
Inject reference solution (a) and the test solution.
Reference solution (b). A 0.01 per cent w/v solution of
Calculate the content ofCzoHz3N04.HCl in the Tablets. nandrolone RS in chloroform.

1750
IP 2010 NANDROLONE PHENYLPROPIONATE

Apply to the plate 5 f.Ll of each solution. After development, Tests


dry the plate in air and examine in ultraviolet light at 254 run. In
Other tests. Complies with the tests stated under Parenteral
the chromatogram obtained with the test solution any spot
Preparations (Injections).
corresponding to nandrolone is not more intense than the
spot in the chromatogram obtained with reference solution Assay. To an accurately measured volume containing about
(b) and any other secondary spot is not more intense than the 0.1 g ofNandrolone Decanoate add sufficient chloroform to
spot in the chromatogram obtained with reference solution (a). produce 100.0 mL Dilute 3.0 ml ofthe solution to 50.0 ml with
chloroform. To 5.0 ml of this solution add 10 ml of isoniazid
Sulphated ash (2.3.18). Not more than 0.1 percent.
solution and sufficient methanol to produce 20.0 ml. Allow to
Loss on drying (2.4.19). Not more than 0.5 per cent, determined stand for 45 minutes and measure the absorbance of the
on 1.0 g by drying over phosphorus pentoxide at a pressure resulting solution at the maximum at about 380 nm (2.4.7),
not exceeding 0.7 kPa for 4 hours. using as the blank 5 ml of chloroform treated in the same
Assay. Weigh accurately about 10 mg and dissolve in sufficient manner. Calculate the content ofC2sH4403 from the absorbance
ethanol (95 per cent) to produce 100.0 mL Dilute 5.0 ml to obtained by repeating the operation using a suitable quantity
50.0 ml with ethanol (95 per cent) and measure the absorbance of nandrolone R8.
ofthe resulting solution at the maximwn at about 239 run (2.4.7). 1 mg ofCIsH2602 is equivalent to 1.562 mg ofC2sH4403.
Calculate the content of C 2s H44 0 3 taking 407 as the specific
Storage. Store protected from light.
absorbance at 239 nm.
Storage. Store protected from light and moisture.

Nandrolone Phenylpropionate
Nandrolone Phenpropionate
Nandrolone Decanoate Injection
Nandrolone Decanoate Injection is a sterile solution of
Nandrolone Decanoate in Ethyl Oleate or other suitable ester,
in a suitable fixed oil or in any mixture ofthese.
Nandrolone Decanoate Injection contains not less than 90.0
per cent and not more than 110.0 per cent ofthe stated amount
ofnandrolone decanoate, C2sH4403.
Usual strength. 25 mg per mL

Identification Mol.Wt. 406.6

Detennine by thin-layer chromatography (2.4.17), coating the Nandrolone Phenylpropionate is 3-oxo-4-estren-17~-yI3­


plate with silica gel GF254. phenylpropionate.

Mobile phase. A mixture of 70 volumes of heptane and Nandrolone Phenylpropionate contains not less than 97.0 per
30 volumes of acetone. cent and not more than 103.0 per cent ofC27H3403, calculated
on the dried basis.
Test solution. Dilute a suitable volume of the injection with
carbon tetrachloride to give a solution containing 0.5 per- Category. Anabolic steroid.
cent w/v solution of Nandrolone Decanoate. Dose. By deep intramuscular injection, 25 to 50 mg weeldy.
Reference solution. A 0.5 per cent w/v solution ofnandrolone Description. A white to creamy-white, crystalline powder;
decanoate RS in carbon tetrachloride. odour, characteristic.
Apply to the plate 5 f.LI of each solution. After development, Identification
dry the plate in air until the odour of solvent is no longer
detectable, spray with a 10 per cent v/v solution of sulphuric A. Detennine by infrared absorption spectrophotometry (2.4.6).
acid in ethanol (95 per cent), heat at 105° for 30 minutes and Compare the spectrum with that obtained with nandrolone
examine in ultraviolet light at 365 run. The principal spot in the phenylpropionate RS or with the reference spectrum of
chromatogram obtained with the test solution corresponds to nandrolone phenylpropionate.
that in the chromatogram obtained with the reference solution. B. When examined in the range 230 run to 360 nm (2.4.7), a
Ignore any subsidiary spots due to the vehicle. 0.001 per cent w/v solution in ethanol (95 per cent) shows an

1751
NANDROLONE PHENYLPROPIONATE IP 2010

absorption maximum only at about 240 nm; absorbance at Nandrolone Phenylpropionate Injection contains not less than
about 240 nm, about 0.43. 92.5 per cent and not more than 107.5 per cent of the stated
C. Dissolve 25 mg in I ml of methanol, add 2 ml of amount of nandrolone phenylpropionate, C27H3403'
semicarbazide acetate solution, heat under a reflux condenser Usual strengths. 25 mg per ml; 50 m per ml.
for 30 minutes and cool; the precipitate, after recrystallisation
f
from ethanol (95 per cent) melts at about 182° (2.4.21). Identification
Tests Dissolve a volume of the injection containing 50 mg of
Nandrolone Phenylpropionate in 8 ml of light petroleum
Specific optical rotation (2.4.22). +48.0 ° to +51.0°, determined (40° to 60°) and extract with three 8-ml quantities ofa mixture
in a 1.0 per cent w/v solution in dioxan. of 7 volumes of glacial acetic acid and 3 volumes of water.
Related substances. Determine by thin-layer chromatography Wash the combined extracts with 10 ml of light petroleum
(2.4.17), coating the plate with silica gel GF254. (40° to 60°), dilute with water until the solution becomes
turbid, allow to stand for 2 hours in ice and filter. The precipitate,
Mobile phase. A mixture of 70 volumes of heptane and
after washing with water and drying over phosphorus
30 volumes of acetone.
pentoxide at a pressure not exceeding 0.7 kPa, complies with
Test solution. Dissolve 0.1 g of the substance under the following test.
examination in 10 ml ofchloroform.
Determine by thin-layer chromatography (2.4.17), using a
Reference solution (a). A 0.005 per cent w/v solution of the silica gel GF254 precoated plate the surface of which has
substance under examination in chloroform. been modified by chemically-bonded octadecylsilyl groups.
Reference solution (b). A 0.01 per cent w/v solution of Mobile phase. A mixture of20 volumes ofwater, 40 volumes
nandrolone RS in chloroform. of acetonitrile and 60 volumes ofpropan-2-01.
Apply to the plate 5 Jll of each solution. After development, Test solution. A 0.5 per cent w/v solution of the dried
dry the plate in air and examine in ultraviolet light at 254 nm. In precipitate in chloroform.
the chromatogram obtained with the test solution any spot
Reference solution (a). A 0.5 per cent w/v solution of
corresponding to nandrolone is not more intense than the
nandrolone phenylpropionate RS in chloroform.
spot in the chromatogram obtained with reference solution
(b) and any other secondary spot is not more intense than Reference solution (b). A mixture of equal volumes ofthe test
the spot in the chromatogram obtained with reference solution and the reference solution.
solution (a). Apply to the plate 5 Jll of each solution. After development,
Sulphated ash (2.3.18). Not more than 0.1 per cent. dry the plate in air until the solvent has evaporated and heat it
at 100° for 10 minutes. Allow to cool and examine in ultraviolet
Loss on drying (2.4.19). Not more than 0.5 per cent, determined
light at 254 nm. The principal spot in the chromatogram
on 1.0 g by drying over phosphorus pentoxide at a pressure
obtained with the test solution corresponds to that in the
not exceeding 0.7 kPa for 4 hours.
chromatogram obtained with reference solution (a). The
Assay. Weigh accurately about 10 mg, dissolve in sufficient principal spot in the chromatogram obtained with reference
ethanol to produce 100.0 ml, dilute 5.0 ml to 50.0 ml with ethanol solution (b) appears as a single spot.
and measure the absorbance of the resulting solution at the
maximum at about 240 nm (2.4.7). Calculate the content of Tests
C27H3403 taking 430 as the specific absorbance at 240 nm.
Other tests. Complies with the tests stated under Parenteral
Storage. Store protected from light. Preparations (Injections).
Assay. To an accurately measured volume containing about
0.1 g of Nandrolone Phenylpropionate add sufficient
chloroform to produce 100.0 ml. Dilute 3.0 ml ofthis solution
Nandrolone Pbenylpropionate to 50.0 ml with chloroform. To 5.0 ml ofthe resulting solution
Injection add 10 ml of isoniazid solution and sufficient methanol to
produce 20.0 ml. Allow to stand for 45 minutes and measure
Nandrolone Phenylpropionate Injection is a sterile solution the absorbance of the solution at the maximum at about
of Nandrolone Phenylpropionate in Ethyl Oleate or other 380 nm (2.4.7), using as blank 5 ml ofchloroform treated in the
suitable ester, in a suitable fixed oil or in a mixture ofthese. same manner. Calculate the content of C27H3403 from the

1752
IP 2010 NAPHAZOLINE NITRATE

absorbance obtained from a 0.006 per cent w/v solution of Tests


nandrolone phenylpropionate RS treated in the same manner.
Appearance of solution. A 1.0 per cent w/v solution in carbon
Storage. Store protected from light. dioxide-free water is clear (2.4.1) and colourless (2.4.1).
Labelling. The label states that the preparation is for
pH (2.4.24).5.0 to 6.5, determined in a 1.0 per cent w/v solution.
intramuscular injection only.
Related substances. Determine by liquid chromatography
(2.4.14).
Test solution. Dissolve 50 mg of the substance under
N aphazoline Nitrate examination in 100 ml ofthe mobile phase.
Reference solution (a). Dissolve 5 mg of 1-naphthylacetic
acid in the mobile phase, add 5 ml of the test solution and
dilute to 100 ml with the mobile phase.
Reference solution (b). Dissolve 5 mg ofnaphazoline impurity
A RS in 100 ml ofthe mobile phase. Dilute 5.0 ml ofthis solution
to 100.0 ml with the mobile phase.
Reference solution (c). Dilute 2.0 ml of the test solution to
Mol. Wt. 273.3 10.0 ml with the mobile phase. Dilute 1.0 ml ofthis solution to
Naphazoline Nitrate is 2-(l-napthylmethyl)-2-imidazoline 100.0 ml with the mobile phase.
nitrate. Chromatographic system
Naphazoline Nitrate contains not less than 99.0 per cent and - a stainless steel column 25 cm x 4.0 mm, packed with
not more than 101.0 per cent of C4HI4N2,HN03 calculated on octadecylsilane bonded to porous silica (4 Jlm),
the dried basis. mobile phase: dissolve 1.1 g of sodium
octanesulphonate in a mixture of 5 volumes ofglacial
Category. Sympathomimetic.
acetic acid, 300 volumes ofacetonitrile and 700 volumes
Description. A white or almost white crystalline powder. ofwater,
flow rate. 1 ml per minute,
Identification spectrophotometer set at 280 nm,
Test A may be omitted iftests B, C andD are carried out. Tests injection volume. 20 Jll.
Band C may be omitted if tests A and D are carried out. Inject reference solution (a). The test is not valid unless the
A. Determine by infrared absorption spectrophotometry (2.4.6). resolution between the peaks due to naphazoline and
Compare the spectrum with that obtained with naphazoline naphazoline impurity B is not less than 5.0. The relative
nitrate RS. retention time with reference to naphazoline for
naphthylacetylethylenediamine (naphazoline impurity A) is
B. When examined in the range 230 nm to 360 nm (2.4.7), a about 0.76, for I-naphthylacetic acid (naphazoline impurity B)
0.002 per cent w/v solution in 0.01 Mhydrochloricacidshows is about 1.27, for 1-naphthylacetonitrile (naphazoline impurity
absorption maxima at about 270 nm, 280 nm, 287 nm and C) is about 2.8, for B-naphazoline (naphazoline impurity D) is
291 nm; absorbances at these maxima are about 0.43,0.50,0.35 about 1.28.
and 0.34 respectively.
Inject the test solution, reference solution (b) and (c). Run the
C. Dissolve about 0.5 mg in 1 ml ofmethanol, add 0.5 ml ofa
chromatogram 3 times the retention time ofthe principal peak.
freshly prepared 5 per cent w/v solution of sodium
In the chromatogram obtained with the test solution the area
nitroprusside and 0.5 ml ofa 2 per cent w/v solution ofsodium
ofthe peak due to naphazoline impurity A is not more than the
.hydroxide, allow to stand for 10 minutes and add 1 ml of a
area ofthe principal peak in the chromatogram obtained with
8 per cent w/v solution ofsodium bicarbonate; a violet colour
reference solution (b) (0.5 per cent). The area of any other
is produced.
secondary peak is not more than 0.5 times the area of the
D. Dissolve about 10 mg in 5 ml ofwater, add 0.2 g ofmagnesium principal peak in the chromatogram obtained with reference
oxide, shake mechanically for 30 minutes, add 10 ml of solution (c) (0.1 per cent). The sum ofall the secondary peaks
chloroform and shake vigorously. Allow to stand, separate is not more than 5 times the area of the principle peak in the
the chloroform layer, filter and evaporate the aqueous layer to chromatogram obtained with reference solution (c) (1.0 per
dryness. The residue gives reaction A for nitrates (2.3.1). cent), Ignore any peak with an area less than 0.25 times the

1753
NAPHAZOLINE· NITRATE IP 2010

area ofthe principal peak in the chromatogram obtained with Naproxen contains not less than 99.0 per cent and not more
reference solution (c) (0.05 per cent). than 101.0 per cent OfC14H1403, calculatedon the dried basis.
Naphthylacetylethylenediamine. D.etermine by thin-layer Category. Nonsteroidal antiinflammatory.
chromatography (2.4.17), coating the plate with silica gel G.
Description. A white oralmost white crystalline powder.
Mobile phase. A mixture of 100 volumes of methanol and
1.5 volumes of strong ammonia solution. Identification
Test solution. Dissolve 0.2 g of the substance under Test A may be omitted iftests Band C are carried out. Tests B
examination in 10 ml of methanOL and C may be omitted if test A is carried out.
Reference solution. A solution containing 2 per cent w/vof A. Determine by infrared absorption spectrophotometry (2.4.6).
naphazoline nitrate RS and 0.01 per cent w/v of Compare the spectrum with that obtained with naproxen RS
naphthylacetylethylenediamine hydrochloride RS. or with the reference spectrum of naproxen.
Apply to the plate 10 III of each solution. After development, B. When examined in the range 230 urn to 350 nm (2.4.7), a 0.04
dry the plate at 105° for 5 minutes, spray with a 0.5 percent per cent w/v solution in methanol shows absorption maxima
w/v solution of ninhydrin in methanol and heat at 105° for at about 262 nm, 271 run, 316 urn and 331 nm. The absorbance
10 minutes. Any spot corresponding to naphthylacetyl- at the maxima are216 to 238, 219 to 241, 61 to 69 and 79 to 87
ethylenediamine hydrochloride in the chromatogram obtained respectively.
with the test solution is not more intense than the
corresponding spot in the chromatogram obtained with the C. Melting range (2.4.21). 154° to 158°.
reference solution. The test is not valid unless the
chromatogram obtained with the reference solution shows Tests
two clearly separated spots.
Appearance of solution. A 5.0 per cent w/v solution in
Chlorides (2.3.12). 15.0 ml ofl.O per cent w/v solution in carbon methanol is clear (2.4.1) and not more intensely coloured than
dioxide-free water complies with the limit test for chlorides reference solution BYS6 (2.4.1).
(375 ppm).
Specific optical rotation (2.4.22). + 59° to + 62°, determined in
Sulphated ash (2.3.18). Not more than 0.1 per cent. a 2.0 per cent w/v solution in ethanol (95 per cent).
Loss on drying (2.4.19). Not more than 0.5 per cent, detennined Enantiomeric purity. Determine by liquid chromatography
on 1.0 g by drying in an oven at 105° for 3 hours. (2.4.14).
Assay. Weigh accurately about 0.2 g, dissolve in 30 ml of NOTE-Protect the solutions from light.
anhydrous glacial acetic acid. Titrate with 0.1 M perchloric
acid, detenriining the end-point potentiometrically (2.4.25). Test solution. Dissolve 25 mg of the substance under
Carry out a blank titration. examination in 50 ml of tetrahydrojitran.Dilute 2,0 ml ofthis
.solution to 20 ml with the mobile phase.
I ml of 0.1 M perchloric acid is equivalent to 0.02733 g of
C4HI4N2,HN03. Reference solution (a). Dilute 2.5 ml ofthe test solution to 100
ml with the mobile phase.
Storage. Store protected from light.
Reference solution (b). Dissolve 5 mg of racemic naproxen
RS in 10 ml of tetrahydrofitran, dilute to 100 ml with the mobile
phase.
Naproxen Chromatographic system
- a stainless steel column 25 cm x 4.6 mm, packed with
silica gel1t-acceptorht-donor for chiral separations (5
JllTI),
- column temperature. 25°,
- mobile phase: a mixture of 5 volumes of glacial acetic
acid, 50 volumes of acetonitrile, 100 volumes of 2-
propanol and 845 volumes of hexane,
CI~1403 Mol. Wt. 230.3
flow rate. 2 ml per minute,
Naproxen is (2S)-2-(6-methoxynaphthalen-2-yl)propionic spectrophotometer set at 263 nm,
acid. - injection volume. 20 Ill.

1754
IP 2010 NAPROXEN ORAL SUSPENSION

Inject reference solution (b). The test is not valid unless the solution (a) (0.1 per cent). The sum ofthe areas ofall impurities
resolution between the peaks due to (2R)-2-(6- is not more than 3 times the area of the principal peak in the
methoxynaphthalen-2-yl) propanoic acid (naproxen impurity chromatogram obtained with reference solution (a) (0.3 per
G) ((R)-enantiomer) and naproxen is not less than 3.0. cent). Ignore any peak with an area less than 0.5 times the area
of the principal peak in the chromatogram obtained with
Inject reference solution (a) and the test solution. Run the
reference solution (a) (0.05 per cent).
chromatogram 1.5 times the retention time of the principal
peak. The area of the peak due to naproxen impurity G is not Heavy metals (2.3.13). 1.0 g complies with the limit test for
more than the area ofthe principal peak in the chromatogram heavy metals, Method B (20 ppm).
obtained with reference solution (a) (2.5 per cent). Sulphated ash (2.3.18). Not more than 0.1 per cent.
Related substances. Determine by liquid chromatography Loss on drying (2.4.19). Not more than 0.5 per cent, determined
(2.4.14). on 1.0 g by drying in an oven at 105° for 3 hours.
NOTE-Protect the solutions from light. Assay. Weigh accurately about 0.2 g and dissolve in a mixture
Test solution. Dissolve 12 mg of the substance under of25 ml of water and 75 ml of methanol. Titrate with 0.1 M
examination in 20 ml ofthe mobile phase. sodium hydroxide using 1 ml of phenolphthalein solution as
indicator.
Reference solution (a). Dilute 1.0 ml of the test solution to 50
ml with the mobile phase. Dilute 1.0 ml ofthis solution to 20.0 1 ml of 0.1 M sodium hydroxide is equivalent to 0.02303 g of
ml with the mobile phase. C,JII403'
Reference solution (b). Dissolve 6 mg of 2-bromo-6- Storage. Store protected from light.
methoxynaphthalene RS (Naproxen impurity N RS), 6 mg of
1-(6-methoxynaphthalen-2-yl)ethanone RS( Naproxen
impurity L RS) and 6 mg of (1RS)-1-(6- methoxynaphthalen-
2-ylJethanol RS (Naproxen impurity K RS) in 10 ml of Naproxen Oral Suspension
acetonitrile. To 1.0 ml of this solution, add 1.0 ml ofthe test
solution and dilute to 50 ml with the mobile phase. Dilute 1.0 Naproxen Oral Suspension is an aqueous suspension of
ml ofthis solution to 20 ml with the mobile phase. Naproxen in a suitable flavoured vehicle.

Chromatographic system Naproxen Oral Suspension contains not less than 90.0 per
- a stainless steel column 10 cm x 4.0 mm, packed with cent and not more than 110.0 per cent ofthe stated amountof
octadecylsilane bonded to porous silica (3 Ilm), naproxen, C14H1403.
- column temperature. 50°, Usual strength. 25 mg per ml.
- mobile phase: a mixture of 42 volumes of acetonitrile
and 58 volumes of a 0.136 per cent w/v solution of Identification
potassium dihydrogen phosphate adjust the pH to 2.0
Evaporate 50 ml ofsolution A obtained in the Assay, to dryness
with orthophosphoric acid,
using a rotary evaporator. The residue complies with the
- flow rate. 1.5 ml per minute,
following tests.
- spectrophotometer set at 230 nm,
- injection volume. 20 Ill. A. Determine by infrared absorption spectrophotometry
(2.4.6).Compare the spectrum with that obtained with naproxen
Inject reference solution (b). The test is not valid unless the
RS or with the reference spectrum ofnaproxen.
resolution between the peaks due to naproxen impurity K and
naproxen is not less than 2.2. The relative retention time with B. When examined in the range 230 nm to 350 nm (2.4.7), a
reference to naproxen for naproxen impurity K is about 0.9, for 0.004 per cent w/v solution in methanol exhibits maxima at 262
naproxen impurity L is about 1.4 and naproxen impurity N is nm,27l nm,316nmand331 nm.
about 5.3.
Tests
Inject reference solution (a), (b) and the test solution. Run the
chromatogram 1.5 times the retention time ofnaproxen impurity pH (2.4.24).2.1 to 4.0.
N. The area ofthe peak due to naproxen impurity L is not more
Related substances. Determine by thin-layer chromatography
than the area ofthe corresponding peak in the chromatogram
(2.4.17), coating the plate with silica gel GF254.
obtained with reference solution (b) (0.1 per cent); the area of
any other secondary peak is not more than the area of the Mobile phase. A mixture of3 volumes of glacial acetic acid,
principal peak in the chromatogram obtained with reference 9 volumes of tetrahydrojU,:an and 90 volumes of toluene.

1755
NAPROXEN ORAL SUSPENSION IP 2010

Test solution. Evaporate solution A obtained in the Assay to B. When examined in the range 230 nm to 350 nm (2.4.7), a
dryness on a rotary evaporator and dissolve the residue in 0.004 per cent w/v solution in methanol exhibits maxima at 262
sufficient methanol to produce a solution containing 5.0 per nm,271 nm,316nmand331 nm.
cent w/v ofnaproxen.
Reference solution. Dilute 1 ml of the test solution to 200 ml Tests
with methanol. Related substances. Determine by thin-layer chromatography
Apply to the plate 10 III of each solution. After development, (2.4.17), coating the plate \yith silica gel GF254.
dry the plate in air and examine under ultraviolet light at 254 Mobile phase. A mixture of 3 volumes of glacial acetic acid,
nm. Any secondary spot in the chromatogram obtained with 9 volumes of tetrahydrofuran and 90 volumes of toluene.
the test solution is not more intense than the spot in the
chromatogram obtained with the reference solution (0.5 per Test solution. Weigh 20 suppositories and cut into small
cent). pieces. Dissolve a quantity of the suppositories containing
0.5 g ofNaproxen in 50 ml of 2,2,4-trimethylpentane and extract
Other tests. Complies with the tests stated under Oral Liquids. with four 25-ml quantities of methanol (80 per cent). Combine
Assay. To a quantity of the oral suspension containing 0.5 g the extracts, add 100 ml ofa2 per cent w/v solution of sodium
ofNaproxen add 20 ml of3.5 M hydrochloric acid; mix, extract chloride, extract with four 25-ml quantities of chloroform
with three 50 ml quantities of chloroform, filter each extract filtering each extract through a layer of anhydrous sodium
through anhydrous sodium sulphate, combine the filtrates sulphate on an absorbent cotton plug moistened with
and add sufficient chloroform to produce 200 ml (solution A). chloroform. Evaporate the combined filtrates to dryness using
To 5 ml of solution A add sufficient methanol to produce 250 a rotary evaporator with the aid of gentle heat. Shake the
ml and measure the absorbance of the resulting solution at residue with 10 ml of methanol, centrifuge and use the
the maximum at about 331 nm (2.4.7). supernatant liquid.
Calculate the content of Cl4Hl403 taking 81 as the specific Reference solution. Dilute1 ml of the test solution to 200 ml
absorbance at 331 nm. with methanol.
Apply to the plate 10 III of each solution. After development,
dry the plate in air and examine under ultraviolet light at 254
nm. Any secondary spot in the chromatogram obtained with
N aproxen Suppositories the test solution is not more intense than the spot in the
chromatogram obtained with the reference solution.
Naproxen Suppositories contain Naproxen in a suitable
Other tests. Comply with the tests stated under Suppositories.
suppository base.
Assay. Determine by liquid chromatography (2.4.14).
Naproxen Suppositories contain not less than 95.0 per cent
and not more than 105.0 per cent of the stated amount of Test solution. Disperse ten suppositories in 500 ml of methanol
naproxen, C14H1403. on a water-bath for 40 minutes with the aid of ultrasound and
by swirling the flask. Cool at 50 for 1 hour, centrifuge and use
Usual strength. 500 mg.
the clear, supernatant liquid; if the solution is still cloudy
Identification filter through glass-fibre paper (such as Whatrnan OFIe). To 5
ml ofthe filtrate add sufficient ofthe mobile phase to produce
Dissolve a quantity of the suppositories containing 0.5 g of a solution containing 0.01 per cent w/v ofnaproxen.
Naproxen in 50 ml of 2,2,4-trimethylpentane and extract with
Reference solution (a). A 0.01 per cent w/v solution of
four 25 ml quantities of methanol (80 per cent). To the
naproxen RS in the mobile phase.
combined extracts add 100 rnl of a 2 per cent w/v solution of
sodium chloride, extract with four 25 ml quantities of Reference solution (b). A 0.01 per cent w/v each ofnaproxen
chloroform, dry the combined extracts over anhydrous sodium RS and 2-naphthylacetic acid in the mobile phase.
sulphate, filter and add sufficient chloroform to produce 200 Chromatographic system
ml (solution A). Evaporate 100 ml of solution A to dryness a stainless steel column 20 cm x 4 mm, packed with end-
using a rotary evaporator. The residue complies with the capped octadecylsilane bonded to porous silica (5 Ilm)
following tests. (such as Nucleosil C18),
A. Determine by infrared absorption spectrophotometry (2.4.6). mobile phase: a mixture of 1 volume of a 0.52 per cent
Compare the spectrum with that obtained with naproxen RS w/v solution of sodium acetate, adjusted to pH 5.8
9r with the reference spectrum of naproxen. using glacial acetic acid and 1 volume of methanol,

1756
IP 2010 NAPROXEN SUSTAINED-RELEASE TABLETS

flow rate. 2 ml per minute, the absorbance obtained from a solution of known
spectrophotometer set at 254 nm, concentration of naproxen RS in the same medium.
- injection volume. 20 Ill. D. Not less than 80 per cent ofthe stated amount ofC14H1403.
Inject reference solution (b). The test is not valid unless the Uniformity of content. Comply with the test stated under
resolution between the peaks due to naproxen and 2- Tablets.
naphthylacetic acid in the chromatogram obtained with the
Determine by liquid chromatography (2.4.14), as described
reference solution (b) is more than 3.0.
under Assay using the following solutions.
Inject reference solution (a) and the test solution.
Test solution. Disperse 1 tablet in about 140 ml of solvent
Calculate the content of CI4HI403 in the suppositories. mixture B. Shake for 15 minutes, sonicate for 15 minutes, dilute
Storage. Store protected from light. to 200 ml with solvent mixture B, filter. Dilute 2.0 ml of the
filtrate to 50 ml with the mobile phase.
Reference solution. A 0.025 per cent wIv solution of naproxen
RS in solvent mixture A. Dilute 10 ml ofthis solution to 25 ml
Naproxen Sustained-release Tablets with solvent mixture B.
Calculate the content ofCI4HI403 in the tablet.
Naproxen Sustained-release Tablets contain not less than 90.0
per cent and not more than 110.0 per cent ofthe stated amount Other tests. Comply with the tests stated under Tablets.
ofnaproxen, C14H1403. Assay. Determine by liquid chromatography (2.4.14).
Usual strength. 375 mg. Solvent mixture A. 90 volumes of acetonitrile and 10 volumes
of water.
Identification
Solvent mixture B. 50 volumes of acetonitrile and 50 volumes
A. When examined in the range 200 TIm to 400 TIm (2.4.7), the of water.
solution used in test B of dissolution, exhibits an absorption
Test solution. Weigh and powder 20 tablets. Disperse a quantity
maximum at about 332 TIm.
of powder containing about 250 mg ofNaproxen in 70 ml of
B. In the Assay, the principal peak in the chromatogram solvent mixture B, sonicate for 15 minutes and dilute to 100.0
obtained with the test solution corresponds to that in the ml with solvent mixture B and filter. Dilute 2.0 ml ofthe filtrate
chromatogram obtained with the reference solution (b). to 50 ml with the mobile phase.
Reference solution (a). A 0.05 per cent wlv solution of
Tests
naproxen RS in solvent mixture A.
Dissolution (2.5.2). Reference solution (b). Dilute 10 ml of reference solution (a)
A. Apparatus No.1, to 50 ml with the mobile phase.
Medium. 1000 ml of0.1 M hydrochloric acid, Chromatographic system
Speed and time. 50 rpm and 2 hours. a stainless steel column 25 cm x 4.6 rom, packed with
octadecylsilane bonded to porous silica (5 11m),
Withdraw a suitable volume ofthe medium and filter. Measure
mobile phase: a mixture of 55 volumes of 1.0 per cent
the absorbance of the filtered solution, suitably diluted with
vlv solution of acetic acid and 45 volumes of
the medium if necessary, at the maximum at about 332 TIm
acetonitrile,
(2.4.7). Calculate the content ofC,4H1403in the medium from
- flow rate. 1ml per minute,
the absorbance obtained from a solution of known
spectrophotometer set at 254 nm,
concentration of naproxen RS in the same medium.
injection volume. 50 Ill.
D. Not more than 10 per cent ofthe stated amount ofC,4H,403.
Inject reference solution (b). The test is not valid unless the
B. Apparatus No.1, tailing factor ofthe principal peak is not more than 1.5 per cent
Medium. 1000 ml of 0.2 M phosphate bujferpH 6.8, and the relative standard deviation for replicate injections is
not more than 2.0 per cent.
Speed and time. 50 rpm and 45 minutes.
Inject the test solution and reference solution (b).
Withdraw a suitable volume ofthe medium and filter. Measure
the absorbance of the filtered' solution, suitably diluted with Calculate the content of CI4HI403 in the tablet.
the medium if necessary, at the maximum at about 332 nm Storage. Store protected from moisture, at a temperature not
(2.4.7). Calculate the content ofC,4H1403 in the medium from exceeding 30°.

1757
NAPROXEN TABLETS IP 2010

Naproxen Tablets Other tests. Comply with the tests stated under Tablets.
Assay. Weigh and powder 20 tablets. Shake a quantity of the
Naproxen Tablets contain not less than 95.0per cent and not
powder containing about 50 mg ofNaproxen with 70 ml of
more than 105.0 per cent of the stated amount ofnaproxen,
methanol for 30 minutes, add sufficient methanol to produce
C14H1403;
100 ml and filter. Dilute 10 ml of the filtrate to 50 ml with
Usual strengths. 250 mg; 500 mg. methanol and measure the absorbance at the maximum at about
331nm (2.4.7) using a 0.01 per cent wlv solution of naproxen
Identification
RS in methanol.
A. Extract a quantity of the powdered tablets containing 20
Calculate the content of CI4HI403 in the tablets.
mg ofNaproxen with 100 ml of methanol and filter. Evaporate
and dry the residue at 105°. On the residue, determine by Storage. Store protected from light.
infrared absorption spectrophotometry (2.4.6). Compare the
spectrum with that obtained with naproxen RS or with the
reference spectmm of naproxen.
Nebivolol Hydrochloride
B. When examined in the range 230 nm to 350 nm (2.4.7), a . . OH·. OH .
0.002 per cent w Iv solution in methanol exhibits maxima at 262
nm,271 nm,316nmand331 nm.
~O~~~O~ ,Hel
Tests F~ ~F
Dissolution (2.5.2). Mol. Wt. 441.9
Apparatus No.1; Nebivolol Hydrochloride is (IRS, 1'RS)-I, 1'-[(2RS,2'SR)-bis (6-
Medium. 900 ml ofa phosphate buffer prepared by dissolving flurochroman-2-yl)]-2,2'-iminodiethanol hydrochloride.
2.62 g of sodium dihydrogen orthophospate monohydrate Nebivolol Hydrochloride contains not less than 98.0 per cent
and 11.5 g of anhydrous disodium hydrogen orthophosphate and not more than 102.0 per cent of C22H2sF2N04,HCl,
in sufficient water to produce 1000 ml, adjusted to pH 7.4 with calculated on the anhydrous basis.
0.1 M sodium hydroxide or 0.1 M hydrochloric acid,
Speed and time. 50 rpm and 45 minutes. Category. Antihypertensive.

Withdraw a suitable volume ofthe medium and filter. Measure Description. A white to off-white powder.
the absorbance of the filtrate, suitably diluted with the Identification
dissolution medium ifnecessary, at the maximum at about 332
mn (2.4.7). Calculate the content ofC,4H,403, in the mediUlp Detennine by infrared absorption spectrophotometry (2.4.6).
from the absorbance obtained from a solution of known Compare the spectrum with that obtained with nebivolol
concentration of naproxen RS in the same medium. hydrochloride RS or with the reference spectrum ofnebivolol
hydrochloride.
D. Not less than 70 percent ofthe stated amount ofC14H1403.
Related substances. Determine by thin-layer chromatography Tests
(2.4.17), coating the plate with silica gel GF254.
Related substances. Determine by .liquid chromatography
Mobile phase. A mixture on volumes of glacial acetic acid, (2.4.14).
9 volumes of tetrahydrofitran and 90 volumes of toluene.
Test solution. Dissolve 30 mg of the substance under
Test solution. Shake a quantity of the powdered tablets examination in 5 ml of acetonitrile and dilute to 100.0 ml with
containing about 0.5 g ofNaproxen with 10 ml of methanol for the mobile phase.
15 minutes, centrifuge and use the supernatant liquid: Reference solution (a). Dissolve 30 mg of nebivolol
Reference solution. Dilute 1 ml of the test solution to 200 ml hydrochloride RS in 5 ml of acetonitrile and dilute to 100.0 ml
with methanol. with the mobile phase.
Apply to the plate 10 /ll of each solution. After development, Reference solution (b). Dilute 1 ml ofreference solution (a) to
dry the plate in air and examine under ultraviolet light at 254 100.0 ml with the mobile phase.
nm. Any secondary spot in the chromatogram obtained with Chromatographic system
the test solution is not more intense than the spot in the - a stainless steel column 25 cm x 4.6 mm, packed with
chromatogram obtained with the reference solution (0.5 per porous silica (5 /lm) with chemically bonded phenyl
cent). groups,

1758
IP 2010 NEBIVOLOL TABLETS

- mobile phase: a mixture of28 volumes of acetonitrile, Identification


72 volumes of a buffer solution prepared by dissolving
3.4 g of tetrabutyl ammonium hydrogen sulphate in In the Assay, the principal peak in the chromatogram obtained
1000 ml wate]; and 0.3 volume of diethylamine, with the test solution corresponds to the peak in the
- flow rate. 1 ml per minute, chromatogram obtained with the reference solution.
- spectrophotometer set at 220 nm,
Tests
- injection volume. 20 ,..t.l.
Inject reference solution (a). The test is not valid unless the Dissolution (2.5.2).
column efficiency in not less than 2000 theoretical plates and Apparatus No.1,
the tailing factor is not more than 2.0. Medium. 500 ml 0,1 M hydrochloric acid,
Inject the test solution and reference solution (b). In the Speed and time. 75 rpm and 30 minutes.
chromatogram obtained with the test solution, the area of any Withdraw a suitable volume ofthe medium and filter.
secondary peak is not more than 0.5 times the area ofthe peak
Detennine by liquid chromatography (2.4.14) as described
in the chromatogram obtained with reference solution (b) (0.5
under Assay using the following solutions and a flow rate of
per cent) and the sum of areas of all the secondary peaks is
not more than the area of the peak in the chromatogram 1.5 ml per minute.
obtained with reference solution (b) (1.0 per cent). Test solution. The filtrate obtained as given above.
Heavy metals (2.3.13). 1.0 g complies with the limit test for Reference solution. A solution containing nebivolol
heavy metals, Method B (20 ppm). hydrochloride RS equivalent to 0.001 per cent w/v of
Sulphated ash (2.3 .18). Not more than 0.2 per cent. nebivolol, in the dissolution medium.
Water (2.3.43). Not more than 1.0 per cent, determined on 0.3 g. D. Not less than 70 per cent of the stated amount of
C22H2sF2N04.
Assay. Determine by liquid chromatography (2.4.14).
Uniformity of content. Comply with the test stated under
Test solution. Dissolve 35 mg of the substance under
examination in 5 ml of acetonitrile and dilute to 50.0 ml with Tablets.
the mobile phase. Dilute 10.0 ml of this solution to 100.0 ml Determine by liquid chromatography (2.4.14), using the
with the mobile phase. chromatographic conditions and the reference solution
Reference solution. Dissolve 35 mg of nebivolol described in the Assay.
hydrochloride RS in 5 ml of acetonitrile and dilute to 50.0 ml Test solution. Disperse one tablet in the mobile phase, dilute
with the mobile phase. Dilute 10.0 ml ofthis solution to 100.0 to obtain a solution containing 0.005 per cent w/v ofnebivolol
ml with the mobile phase. in the mobile phase and filter.
Use the chromatographic system described under Related Calculate the content of C22H25F2N04 in the tablets.
substances.
Other tests. Comply with the tests stated under Tablets.
Inject the reference solution. The test is not valid unless the Assay. Determine by liquid chromatography (2.4.14).
relative standard deviation for replicate injections is not more
than 2.0 per cent. Test solution. Weigh and powder 20 tablets. Weigh accurately
a quantity of the powder containing about 5 mg ofnebivolol,
Inject the test solution and the reference solution. disperse in 100.0 ml ofthe mobile phase and filter.
Calculate the content ofC22H25F2N04,HCl. Reference solution. A solution containing nebivolol
Storage. Store protected from moisture, at a temperature not hydrochloride RS equivalent to 0.005 per cent w/v of
exceeding 30°. nebivolol, in the mobile phase.
Chromatographic system
a stainless steel column 25 cm x 4.6 mm, packed with
Nebivolol Tablets octadecylsilane bonded to porous silica (5 /lm),
Nebivolol Hydrochloride Tablets mobile phase: a mixture of45 volumes ofa buffer solution
prepared by dissolving 6.8 g of potassium dihydrogen
Nebivolol Tablets contain not less than 90.0 per cent and not
orthophosphate in 1000 ml of wate]; adding 2 ml of
more than 110.0 per cent of the stated amount ofnebivolol,
triethylamine and adjusting the pH to 3.0 with 10 per
C22H25F2N04. cent v/v orthophosphoric acid, 25 volumes of
Usual strength. 5 mg acetonitrile and 30 volumes of methanol,

1759
NELFINAVIR MESYLATE IP 2010

- flow rate. 1 ml per minute, Tests


- spectrophotometer set at 281 nm,
- injection volume. 20 111. Specific optical rotation (2.4.22). -105 0 to -120 0 , determined
in a 1.0 per cent w/v solution in methanol.
Inject the reference solution. The test is not valid unless the
relative standard deviation for replicate injections is not more Related substances. Determine by liquid chromatography
than 2.0 per cent. (2.4.14), using the chromatographic system described in the
Assay.
Inject the test solution and the reference solution.
Test solution. A 0.1 per cent w/v solution of the substance
Calculate the content of C22H2SF2N04 in the tablets, under examination in the mobile phase.
Storage. Store protected from light and moisture. Reference solution (a). A 0.001 per cent w/v solution of the
Labelling. The label states the strength in terms of the substance under examination in the mobile phase.
equivalent amount of nebivolol. Reference solution (b). A 0.01 per cent w/v solution of
methanesulphonic acid in the mobile phase.
Inject reference solution (a). The test is not valid unless the
column efficiency determined from the nelfinavir peak is not
Nelfinavir Mesylate , less than 4000 theoretical plates and the tailing factor is not
more than 2.0.
Separately inject reference solution (b) and record the
chromatograms. Separately inject the test solution and
continue the chromatography for at least three times the
retention time of the principal peak. In the chromatogram
obtained with the test solution, the area of any peak other
than the principal peak is not greater than half of the area of
the principal peak in the chromatogram obtained with reference
solution (a) (0.5 per cent) and the sum of the areas of all such
peaks is not greater than the area of the principal peak in the
chromatogram obtained with reference solution (a) (1.0 per
C32~sN304S,C~03S Mol. Wt. 663.9 cent). Ignore any peak due to methanesulphonic acid
corresponding to the retention time of the principal peak in
Nelfinavir Mesylate is (3S,4aS,8aS)-N-(tert-butyldecahydro- the chromatogram obtained with reference solution (b).
2-[(2R,3R)-3-(3-hydroxy-o-toluamido)-hydroxy-4-
(phenylthio)butyl]isoquinoline-3-carboxamide methyl Methanesulphonic acid. 13.5 per cent to 15.5 per cent w/w,
sulphonate. calculated on the anhydrous basis, determined by the following
method. Weigh accurately about 0.6 g, dissolve in 50 ml of
Nelfinavir Mesylate contains not less than 98.0 per cent and dimethylformamide and titrate with 0.1 M sodium hydroxide,
not more than 101.0 per cent of C32H4SN304S,CH403S, determining the end-point potentiometrically (2.4.25). Carry
calculated on the anhydrous basis. out a blank titration.
Category. Antiretroviral.
1 ml of 0.1 Msodium hydroxide is equivalentto 0.00961 g of
Dose. 1.25 g twice daily. CH3S03H.
Description. A white or almost white powder. Heavy metals (2.3.13). 1.0 g complies with the limit test for
heavy metals, Method B (20 ppm).
Identification Sulphated ash (2.3 .18). Not more than 0.1 per cent.
A. Determine by infrared absorption spectrophotometry (2.4.6). Water (2.3.43). Not more than 3.0 percent, determined on 0.5 g.
Compare the spectrum with that obtained with neljinavir
Assay. Determine by liquid chromatography (2.4.14).
mesylate RS or with the reference spectrum of nelfinavir
mesylate. Test solution. A 0.01 per cent w/v solution of the substance,
B. In the Assay, the principal peak in the chromatogram under examination in the mobile phase.
obtained with the test solution corresponds to the peak in the Reference solution. A 0.01 per cent w/v solution ofneljinavir
chromatogram obtained with the reference solution. mesylate RS in the mobile phase.

1760
IP 2010 NELFINAVIR MESYLATE ORAL POWDER

Chromatographic system Use the chromatographic system described under Assay.


a stainless steel column 25 em x 4.6 rom, packed with
Inject the test solution and the reference solution.
octadecylsilane bonded to porous silica (5 /lm),
mobile phase: a filtered and degassed mixture of D. Not less than 75 per cent of the stated amount of
45 volumes of acetonitrile, 20 volumes of methanol C32~5N304S,
and 35 volumes ofa buffer prepared by dissolving 4.0 g
Related substances. Determine by liquid chromatography
of sodium dihydrogen phosphate in 1000 ml of water,
(2.4.14).
to which 1 ml of dimethylamine solution and 1 g of
sodium octanesulphonate are added and mixed to "Test solution. Weigh accurately a quantity of the oral powder
dissolve, containing 50 mg ofNelfinavir Mesylate, disperse in 10 ml of
flow rate. 1 ml per minute, methanol, dilute to 50 ml with the mobile phase and filter.
spectrophotometer set at 215 nm, Reference solution (a). Dissolve 10 mg of nelfinavir mesylate
injection volume. 20 Ill. RS in 2 ml of methanol and dilute to 10 ml with the mobile
Inject the reference solution. The test is not valid unless the phase.
column efficiency determined from the nelfinavir peak is not Reference solution (b). Dilute 1 ml ofreference solution (a) to
less than 5000 theoretical plates, the tailing factor is not more 100 ml with the mobile phase.
than 2.0 and the relative standard deviation for replicate
injections is not more than 2.0 per cent. Chromatographic system
a stainless steel column 15 em x 4.6 mm, packed with
Separately inject the test solution and the reference solution octadecylsilane bonded to porous silica (5 /lm),
and measure the responses for the principal peak. Calculate column temperature. 45°,
the content ofC32H45N304S,CH403S. mobile phase: a mixture of 28 volumes ofa buffer solution
Storage. Storeprotected from light. prepared by dissolving 4.88 g of anhydrous sodium
dihydrogen phosphate in 1000 ml of water, adjusting
the pH to 3.4 with phosphoric acid and filtering,
27 volumes of acetonitrile, 20 volumes of methanol
Nelfinavir Mesylate Oral Powder and 25 volumes of water. Adjust the pH to 4.8 with
0.1 M sodium hydroxide or orthophosphoric acid.
Nelfinavir Mesylate Oral Powder contains not less than
flow rate. 1 ml per minute,
90.0 per cent and not more than 110.0 per cent of the stated
spectrophotometer set at 220 nm,
amount ofnelfinavir, C32~5N304S,
injection volume. 10 Ill.
Usual strength. 50 mg per g.
Inject the reference solution (a). The test is not valid unless
the tailing factor is not more than 2.0 and the column efficiency
Identification
in not less than 4000 theoretical plates.
In the Assay, the principal peak in the chromatogram obtained Inject the test solution and reference solution (b). In the
with the test solution corresponds to the peak in the chromatogram obtained with the test solution, the area of any
chromatogram obtained with the reference solution. secondary peak is not more than the area of the peak in the
Tests chromatogram obtained with the reference solution (b)
(1.0 per cent) and the sum of areas of all the secondary peaks
Dissolution (2.5.2). is not more than twice the area ofthe peak in the chromatogram
Apparatus. No 1 obtained with the reference solution (b) (2.0 per cent).
Medium. 900 ml of 0.1 M hydrochloric acid. Water (2.3.43). Not more than 12.0 per cent, determined on
Speed and time. 75 rpm and 45 minutes. 0.5g.
Withdraw a suitable volume ofthe medium and filter. Assay. De~'rmine by liquid chromatography (2.4.14).
Determine by liquid chromatography (2.4.14). Solvent mixture. 30 volumes of water and 70 volumes of
Test solution. Use the filtrate and, ifnecessary, dilute with the methanol.
dissolution medium. Test solution. Weigh accurately a quantity of the powder
Reference solution. A 0.065 per cent w Iv solution of nelfinavir containing 50 mg ofNelfinavir Mesylate, disperse in 50 ml of
mesylate RS in methanol. Dilute 10 ml ofthe solution to 100 ml 0.1 M hydrochloric acid, dilute to 250.0 ml with the solvent
with the dissolution medium. mixture and filter.

1761
NELFINAVIR MESYLATE ORAL POWDER IP 2010

Reference solution. Dissolve 10 mg ofneljinavir mesylate RS Tests


in 10 ml ofO.1Mhydrochloric acid and dilute to 50.0 ml with
the solvent mixture. Dissolution (2.5.2).
Apparatus No.1,
Chromatographic system
Medium. 900 mlofO.OI Mhydrochloric acid,
a stainless'steel column 15 cm x 4.6 mm,packed with
octadecylsilane bonded to porous silica (5 /lm), Speed and time. 50 rpm and 30 minutes.
- column temperature 40°, Withdraw a suitable volume ofthe medium and filter promptly
mobile phase: a mixture of 35 volumes ofa buffer solution through a membrane filter disc with an average pore diameter
prepared by dissolving 4 g of sodium dihydrogen not greater than 1.0 /lm. Reject the first few ml ofthefiltrate
phosphate dihydrate and 1g of I-octane sulphonic and dilute a suitable volume of the filtrate with the same
acid sodium salt into 1000 ml of water, adding 1ml of solvent. Measure the absorbance of the resulting solution at
dimethylamine and filtering, 45 volumes acetonitrile the maximum at about 250 nm (2.4.7). Calculate the content of
and 20 volumes of methanol, C32H4SN304S,CH403S from the absorbance of a solution of
flow rate. 2 ml per minute, known concentration of neljinavir mesylate RS.
spectrophotometer set at 220 nm, D. Not less thau 75 per cent of the stated amount of
iIljection volume. 10 Ill. C32~sN304S,C~03S,
Inject the reference solution. The test is not valid unless the Related substances. Determine by liquid chromatography
tailing factor is not more than 2.0, the column efficiency in not (2.4.14).
less than 2000 theoretical plates and the relative standard
Test solution. Weigh accurately a quantity of the powdered
deviation for replicate injections is not more than 2.0 per cent.
tablets containing about 100 mg ofNelfinavir Mesylate, add
Inject the test solution and the reference solution. about 20 ml of methanol, mix with the aid of ultrasound for
Calculate the content of C32H4SN304S in the oral powder. 10 minutes and dilute to 100 ml with.the mobile phase.

Storage. Store protected from moisture, at a temperature not Reference solution. Weigh accurately about 10 mg of
exceeding 30°. neljinavir mesylate RS, add about 10 ml of methanol, shake
for 10 minutes and dilute to 50 ml with the mobile phase.
Labelling. The label states the strength in terms of the
Chromatographic system
equivalent amount ofnelfinavir.
a stainless steel column 25 cm x 4.6 mm, packed with
octadecylsilane bonded to porous silica particles or
ceramic microparticles (5 /lm),
- mobile phase: a filtered and degassed mixture of
Nelfinavir Tablets 45 volumes of acetonitrile, 20 volumes of methanol
and 35 volumes ofa buffer prepared by dissolving 4.0 g
Nelfinavir Mesylate Tablets
of sodium dihydrogen phosphate in 1000 ml of water,
Nelfinavir Tablets contain not less than 90.0 per cent and not to which are added 1 ml of dimethylamine solution and
more than 110.0 per cent of the stated amount of nelfinavir 1 g of sodium octanesulphonate and mixing to dissolve,
mesylate, C32H4SN304S,CH403S. flow rate. 1 ml per minute,
Usual strengths. 250 mg; 625 mg. - spectrophotometer set at 215 urn,
injection volume. 20 Ill.
Identification Inject the reference solution. The test is not valid unless the
column efficiency determined from the nelfinavir mesylate peak
A. Shake a quantity ofthe powdered tablets containing about is not less than 4000 theoretical plates and the tailing factor is
0.1 g of Nelfinavir Mesylate with 80 ml of methanol for not more than 2.0.
10 minutes, add sufficient methanol to produce 100 ml, mix
Inject separately the diluent (10 ml of methanol diluted to
and filter. Dilute 5 ml ofthe filtrate to 100 ml with methanol.
50 ml with the mobile phase) and the test solution and continue
When examined in the range 200 nm to 300 urn the resulting the chromatography for 4 times the retention time of the
solution shows an absorption maximum only at about 254 nm principal peak. Examine the diluent chromatogram Jor any
(2.4.7). extraneous peaks and ignore the corresponding peaks
observed in the chromatogram obtained with the test solution.
B. In the Assay, the principal peak in the chromatogram
obtained with the test solution corresponds to the peak in the Any secondary peak observed in the chromatogram obtained
chromatogram obtained with the reference solution. with the test solution should not be more than 1.0 per cent

1762
IP 2010 NEOMYCIN SULPHATE

and the sum of the areas of all the secondary peaks should Mobile phase. A freshly prepared 3.85 per cent w/v solution
not be more than 2.0 per cent when calculated by percentage of ammonium acetate.
area normalisation. Inhibit integration of peak due to
Test solution. Dissolve 0.2 g of the substance under
methanesulphonic acid.
examination in 10 ml of water.
Other tests. Complies with the tests stated under Tablets.
Reference solution. A 2.0 per cent w/v solution of neomycin
Assay. Determine by liquid chromatography (2.4.14). sulphate RS in water.
Test solution. Weigh accurately a quantity of the powdered Apply to the plate 1 III of each solution. After development,
tablets containing about 200 mg ofNelfinavir Mesylate, add dry the plate in air for 10 minutes, heat at 100 0 for 1 hour and
about 20 ml of methanol, mix with the aid of ultrasound for spray with a 0.1 per cent w/v solution of ninhydrin in
10 minutes and dilute to 100.0 ml with the mobile phase. Filter I-butanol saturated with water. Heat again at 100 0 for
through a membrane filter disc with an average pore diameter 5 minutes. The principal spot in the chromatogram obtained
not greater than 1.0 11m, rejecting the first few ml ofthe filtrate. with the test solution corresponds to that in the chromatogram
Further dilute 5.0 ml ofthe filtrate to 100.0 ml with the mobile obtained with the reference solution.
phase.
B. Dissolve about 10 mg in 5 ml ofwater, add 0.1 ml ofpyridine
Reference solution. Weigh accurately about 50 mg of and 2 ml of a 0.1 per cent w/v solution of ninhydrin and heat
neifinavir mesylate RS, add about 10 ml ofmethanol, mix with on a water-bath at a temperature of about 70 0 for 10 minutes;
the aid ofultrasound to dissolve and dilute to 50.0 ml with the a deep violet colour is produced.
mobile phase. Dilute 5.0 ml ofthis solution to 50.0 ml with the
C. A 5 per cent w/v solution gives the reactions of sulphates
mobile phase.
(2.3.1).
Use the chromatographic system described in the test for
Related substances. Tests
Inject the reference solution. The test is not valid unless the
pH (2.4.24). 5.0to 7.5, determined in a 1.0 percentw/v solution.
column efficiency determined from the nelfmavir mesylate peak
is not less than 5000 theoretical plates, the tailing factor is not Specific optical rotation (2.4.22).+53.5 0 to +59.0 0 , determined
more than 2.0 and the relative standard deviation for replicate in a 10.0 per cent w/v solution.
injections is not more than 2.0 per cent.
Neamine. Determine by thin-layer chromatography (2.4.17),
Inject separately the test solution and the reference solution coating the plate with silica gel H
and measure the responses for the major peale Calculate the
Mobile phase. A mixture of 30 volumes of methanol, 20
content ofC32H4sN304S,CH403S in the tablets.
volumes of strong ammonia solution and 10 volumes of
Storage. Store protected from light. dichloromethane.
Test solution. Dissolve 0.25 g of the substance under
examination in 10 ml of water.
Neomycin Sulphate Reference solution. A 0.05 per cent w/v solution of neamine
Neomycin Sulphate is a mixture ofthe sulphates ofsubstances RSin water.
obtained by the growth of certain selected strains of Apply to the plate as 5-mm bands 5 III of each solution. Dry
Streptomyces fradiae. the bands; allow the mobile phase to rise at least 8 cm. Dry the
Neomycin Sulphate has a potency of not less than 600 Units plate in a current ofwann air, heat at 1100 for 10 minutes, spray
per mg, calculated on the dried basis. the plate with ninhydrin and stannous chloride reagent and
heat at 1100 for 15 minutes. Spray the plate again with the
Category. Antibacterial (topical and systemic). same reagent and heat at 110 0 for 15 minutes. Any band
Dose. 1 g every 4 hours. corresponding to neamine in the chromatogram obtained with
the test solution is not more intense than the spot in the
Description. A white or yellowish-white powder; odourless
chromatogram obtained with the reference solution.
or almost odourless; hygroscopic.
Neomycin C. Determine by thin-layer chromatography (2.4.17),
Identification coating the plate with silica gel of a suitable grade.
A. Determine by thin-layer chromatography (2.4.17), coating Mobile phase. A mixture of 80 volumes of a 20 per cent w/v
the plate with silica gel H solution of sodium chloride and 20 volumes of methanol.

1763
NEOMYCIN SULPHATE IP 2010

Test solution. Dissolve 40 mg of the substance under Mobile phase. A mixture of 60 volumes of methanol,
examination in water and dilute to 5 ml with the same solvent. 40 volumes of strong ammonia solution and 20 volumes of
Reference solution (a). Dissolve 30 mg ofjramycetin sulphate chloroform.
RS in water and dilute to 25 ml with the same solvent. Test solution. Dilute ifnecessary a volume ofthe eye drops to
produce a solution containing 0.5 per cent w/v of Neomycin
Reference solution (b). Dilute 5 ml ofreference solution (a) to
Sulphate in water.
25 ml with water.
Reference solution (a). A 0.5 per cent w/v solution of
Reference solution (c). Dissolve 40 mg of neomycin sulphate
neomycin sulphate RS in water.
RS in water and dilute to 5 ml with the same solvent.
Reference solution (b). A mixture of equal volumes ofthe eye
Apply to the plate as 5 mm bands 5 J..Ll of each solution. Dry
drops and reference solution (a).
the bands; allow the mobile phase to rise at least 12 cm. Dry
the plate at 100° to 105° for 10 minutes. Spray the plate with Apply to the plate 1 J..Ll of each solution. After development,
ethanolic ninhydrin solution and heat at 100° to 105° for dry the plate in air, spray with a 1 per cent w/v solution of
10 minutes. In the chromatogram obtained with the test ninhydrin in I-butanol and heat at 105° for 2 minutes. The
solution the principal band corresponds to the principal band principal red spot in the chromatogram obtained with the test
in the chromatogram obtained with reference solution (c) and solution corresponds to that in the chromatogram obtained
the band due to neomycin C with Rf value slightly less than with reference solution (a) and the principal red spot in the
that of the principal band is not more intense than the band chromatogram obtained with reference solution (b) appears
obtained with reference solution (a) (15 per cent) but is more as a single spot.
intense than the band in the chromatogram obtained with
reference solution (b) (3 per cent). The test is not valid unless Tests
in the chromatogram obtained with reference solution (c) a Neamine. Determine by thin-layer chromatography (2.4.17),
band appears with R f value slightly less than that of the coating the plate with silica gel H
principal band.
.Mobile phase. A mixture of 30 volumes of methanol,
Sulphated ash (2.3.18). Not more than 1.0 per cent. 20 volumes of strong ammonia solution and 10 volumes of
Loss on drying (2.4.19). Not more than 8.0 per cent, determined dichloromethane.
on 0.5 g by drying in an oven at 60° over phosphoruspentoxide Test solution. A volume of the eye drops containing 5 J..Lg
at a pressure not exceeding 0.7 kPa for 3 hours. (3.5 Units).
Assay. Determine by the microbiological assay ofantibiotics, Reference solution. The same volume of water containing
Method A (2.2.1 0). 0.1 J..Lg ofneamine RS.
Storage. Store protected from light and moisture. Apply to the plate each solution. After development, dry the
Labelling. The label states the strength in terms of Units of plate in a current ofwarm air, heat at 110° for 10 minutes, spray
neomycin per mg. the plate with ninhydrin and stannous chloride reagent and
heat at 11 0° for 15 minutes. Spray the plate again with the
same reagent and heat at 110° for 15 minutes. Any spot
corresponding to neamine in the chromatogram obtained with
Neomycin Eye Drops the test solution is not more intense than the spot in the
chromatogram obtained with the reference solution.
Neomycin Sulphate Eye Drops
Neomycin C. Determine by liquid chromatography (2.4.14).
Neomycin Sulphate Eye Drops are a sterile solution of
Neomycin Sulphate in Purified Water. Test solution. Dilute the eye drops with 0.02 M borax to
contain 1 mg (700 Units) per mI. To 0.5 mI ofthe diluted solution
Neomycin Sulphate Eye Drops contain not less than 90.0 per add 1.5 ml of a freshly prepared 2 per cent w/v solution of
cent and not more than 115.0 per cent w/v ofthe stated amount I-jluoro-2,4-dinitrobenzene in methanol, dilute to 25 ml with
of neomycin sulphate. the mobile phase, allow to stand and use the clear lower layer.
Usual strength. 0.5 per cent w/v (3500 Units per ml). Reference solution. Add 1.5 ml of the 1-fluoro-2,4-
dinitrobenzene solution to 0.5 ml ofa 0.1 per cent w/v solution
Identification
of neomycin sulphate RS in 0.02 M borax, heat in a water-
Determine by thin-layer chromatography (2.4.17), coating the bath at 60° for 1 hour and cool; dilute the solution to 25 ml with
plate with silica gel. the mobile phase, allow to stand and use the clear lower layer.

1764
IP 2010 NEOMYCIN EYE OINTMENT

Chromatographic system Usual strength. 0.5 per cent w/w (3500 Units per g).
a stainless steel column 20 em x 4.6 mm, packed with
porous silica particles (5 /-lm) (such as NucleosiI100-5), Identification
- mobile phase: a mixture of 97 ml of tetrahydrofuran, Determine by thin-layer chromatography (2.4.17), coating the
1.0 ml of water and 0.5 ml of glacial acetic acid diluted plate with silica gel.
with sufficient of a 2.0 per cent v/v solution of ethanol
Mobilephase. A mixture of60 volumes of methanol, 40 volumes
in ethanol-free chloroform to produce 250 ml,
of strong ammonia solution and 20 volumes of chloroform.
flow rate. 1.6 m1 per minute,
- spectrophotometer set at 350 nm, Test solution. Disperse a quantity of the eye ointment
- injection volume. 10 Ill. containing 20 mg ofNeoinycin Sulphate in 20 ml of chloroform,
extract with 5 ml of water and use the aqueous extract.
If necessary the tetrahydrofuran and water content of the
mobile phase may be adjusted so that the chromatogram Reference solution (a). A 0.4 per cent w/v solution of
obtained with the reference solution shows resolution similar neomycin sulphate RS in water.
to that in the specimen chromatogram supplied withframycetin Reference solution (b). A mixture of equal volumes of test
sulphate RS. The mobile phase should be passed through the solution and reference solution (a).
column for several hours before the solutions are injected.
Continue the chromatography for 1.4 times the retention time Apply to the plate 1 /-ll of each solution. After development,
dry the plate in air, spray with a 1 per cent w/v solution of
ofthe peak due to neomycin B.
ninhydrin in i-butanol and heat at 105° for 2 minutes. The
The column efficiency, determined using the peak due to principal red spot in the chromatogram obtained with the test
Neomycin B in the chromatogram obtained with the test solution corresponds to that in the chromatogram obtained
solution, should be not less than 13,000 theoretical plates. with reference solution (a) and the principal red spot in the
In the chromatogram obtained with the test solution the area chromatogram obtained with reference solution (b) app~ars
of the peak corresponding to neomycin C is not less than as a single spot.
3.0 per cent and not more than 15.0 per cent ofsum ofthe areas Tests
ofthe peaks corresponding to Neomycin B and Neomycin C.
Neamine. Determine by thin-layer chromatography (2.4.17),
Other tests. Complies with the tests stated under Eye Drops.
coating the plate with silica gel H.
Assay. Measure accurately a quantity containing 5 mg of Mobile phase. A mixture of 30 volumes of methanol,
Neomycin Sulphate and dilute to 50.0 ml with sterile phosphate 20 volumes of strong ammonia solution and 10 volumes of
bufferpH 8.0 and mix. Dilute 10.0 ml ofthe resulting solution dichloromethane.
to 100.0 ml with the same solvent.
Test solution. Disperse a quantity of the eye ointment
Determine by the microbiological assay ofantibiotics, Method containing 20 mg ofNeomycin Sulphate in 20 m1 of chloroform,
A (2.2.10) shake gently with 8 ml of water, allow the layers to separate
The upper fiducial limit of error is not less than 90.0 per cent and use the aqueous layer.
and the lower fiducial limit oferror is not more than 115.0 per Reference solution. A 0.005 per cent w/v solution of neamine
cent of the stated number of Units per ml. RSin water.
Storage. Store protected from light. Apply to the plate 2 /-l1 of each solution. After development,
Labelling. The strength is stated in terms of percentage w/v dry the plate in a current ofwarm air, heat at 110° for 10 minutes,
as well as the number ofUnits per ml. spray with ninhydrin and stannous chloride reagent and
heat at 110° for 15 minutes. Spray the plate again with the
same reagent and heat at 1l0° for 15 minutes. Any spot
corresponding to neamine in the chromatogram obtained with
Neomycin Eye Ointment the test solution is not more intense than the spot in the
chromatogram obtained with the reference solution.
Neomycin Sulphate Eye Ointment
Neomycin C. Determine by liquid chromatography (2.4.17)
Neomycin Sulphate Eye Ointment is a sterile preparation
Test solution. Disperse a quantity of the eye ointment
containing Neomycin Sulphate in a suitable basis.
containing 5 mg of Neomycin Sulphate in 20 ml of light
Neomycin Sulphate Eye Ointment contains not less than petroleum (120° to 160°), add 5 m1 of 0.02 Mborax, shake,
90.0 per cent and not more than 115.0 per cent of the stated separate the aqueous layer and centrifuge. To 0.5 m1 of the
amount of neomycin sulphate. separated aqueous layer add 1.5 ml ofa freshly prepared 2 per

1765
NEOMYCIN EYE OINTMENT IP 2010

cent w/v solution of I-jluoro-2,4-dinitrobenzenein methanol, Neostigmine Bromide


heat on a water-bath at 60° for 1 hour and cool. Dilute the
resulting solution to 25 ml with the mobile phase, allow to
stand and use the clear lower layer.
Refaence solution. Add 1.5 ml of the I-fluoro-2,4-
dinitr,obenzene solution to 0.5 ml ofa 0.1 per cent w/v solution
of neomycin sulphate RS in 0.02 M borax and proceed as for
the test solution.
Chromatographic system
a stainless steel column 20 cm x 4.6 mm, packed with
porous silica particles (5 Ilm), Mol. Wt. 303.2
mobile phase: 97 ml of tetrahydrojitran, 1.0 ml of water
Neostigmine Bromide is 3-(dimethylcarbamoyloxy)
and 0.5 ml of glacial acetic acid with sufficient of a
trimethylanilinium bromide.
2.0 per cent v/v solution of ethanol in ethanol-free
chloroform to produce 250 ml, Neostigmine Bromide contains not less than 98:0 per cent and
- flow rate. 1.6 ml per minute, not more than 101.0 per cent ofClzH19BrNzOz, calculated on
- spectrophotometer set at 350 run, the dried basis.
- injection volume. 10 Ill. Category. Anticholinesterase.
If necessary the tetrahydrofuran and water content of the
Dose. 15 to 30 mg, repeated at suitable intervals; total daily
mobile phase may be adjusted so that the chromatogram
dose, 75 to 300 mg.
obtained with reference solution shows resolution similar to
that in the specimen chromatogram supplied withji-amycetin Description. Colourless crystals or a white, clystalline powder;
sulphate RS. The mobile phase should be passed through the odourless; hygroscopic.
column for several hours before the solutions are injected.
Continue the chromatography for 1.4 times the retention time
Identification
of the peakdue to neomycin B. Test A may be omitted if tests B, C, D and E are carried out.
The column efficiency, determined using the peak due to Tests B, C and D may be omitted if tests A and E are carried
Neomycin B in the chromatogram obtained with the test out.
solution, should be not less than 13,000 theoretical plates. A. Detennine by infrared absorption spectrophotometly (2.4.6).
In the chromatogram obtained with the test solution the area Compare the spectrum with that obtained with neostigmine
of the peak corresponding to neomycin C is not less than bromide RS.
3.0 per cent and not more than 15.0 per cent ofthe sum ofthe B. When examined in the range 230 nm to 360 nm (2.4.7), a
areas ofthe peaks corresponding to Neomycin B and Neomycin 0.02 per cent w/v solution in 0.5 M sulphuric acid shows
C. absorption maxima at about 260 nm and 266 nm.
Other tests. Complies with the tests stated under Eye C. Warm about 50 mg with 1 ml of dilute sodium hydroxide
Ointments. solution; an odour of dimethylamine develops slowly.
Assay. Weigh accurately a quantity containing 5 mg of D. Warm about 50 mg with 0.4 g ofpotassium hydroxide and
Neomycin Sulphate, dissolve in 25 ml of chloroform, extract 2 ml of ethanol (95 per cent) on a water-bath for 3 minutes,
with four quantities, each of20 ml, of sterile phosphate buffer replacing the evaporated ethanol. Cool, add 2 ml of dilute
pH 8.0, combine the extracts and add sufficient of the buffer diazobenzenesulphonic acid solution; an orange-red colour
solution to produce 100.0 ml. is produced.
Cany out the microbiological assay of antibiotics, Method A E. Gives the reactions ofbromides(2.3.1).
(2.2.10).
The upper fiducial limit of error is not less than 90.0 per cent Tests
and the lower fiducial limit ofelTor is not more than 115.0 per Appearance of solution. A 0.5 per cent w/v solution is clear
cent of the stated number of Units per g. (2.4.1), and colourless (2.4.1).
Storage. Store protected from light. Acidity. Dissolve 0.2 g in20 ml of carbondioxide-free water
Labelling. The strength is stated in terms of percentage w/v and titrate to pH 7.0 with 0.02 Msodium hydroxide (carbonate-
as well as the number of Units per ml. free); not more than 0.1 ml is required.

1766
IP 2010 NEOSTIGMINE METHYLSULPHATE

3-Hydroxytrimethylanilinium bromide. Dissolve 50 mg in a Bromide, transfer to a semi-micro ammonia-distillation


mixture of 1 ml of sodium carbonate solution and 9 ml of apparatus, add 20 ml of a 50 per cent w/v solution of sodium
water. Absorbance of the resulting solution at about 294 nm, hydroxide and 0.5 ml ofa 2 per cent w/v solution of 2-octanol
measured immediately after preparation, not more than in liqUidparaffin. Pass a current ofsteam through the mixture,
0.25 (2.4.7). . collect the distillate in 50 ml of 0.01 Msulphuric acid until the
volume is about 200 ml and titrate the excess of acid with
Sulphates (2.3.17). 0.75 g complies with the limit test for
sulphates (200 ppm). 0.02 M sodium hydroxide using methyl red solution as
indicator. Repeat the operation without the substance unde~'
Sulphated ash (2.3.18). Not more than 0.1 percent. examination. The difference between the titrations represents
Loss on drying (2.4.19). Not more than 1.0 per cent, detennined the amount of sulphuric acid required to neutralise the
on 1.0 g by drying in an oven at 105°. dimethylamine produced.

Assay. Weigh accurately about 0.5 g, dissolve in 20 ml of 1 ml of 0.01 M sulphuric acid is equivalent to 0.006064 g of
anhydrous glacial acetic acid, add 5 ml of acetic anhydride. C12H19BrN202'
Titrate with 0.1 M perchloric acid, using crystal violet Storage. Store protected from light and moisture.
solution as indicator. Carry out a blank titration.
1 ml of 0.1 M perchloric acid is equivalent to 0.03032 g of
C,2HI9BrN202. Neostigmine Methylsnlphate
Storage. Store protected from light and moisture.
Mol. Wt. 334.4
Neostigmine Methylsulphate is 3-(dimethylcarbamoyloxy)-
trimethylanilinium methyl sulphate.
Neostigmine Tablets
Neostigmine Methylsulphate contains not less than 98.5 per
Neostigmine Bromide Tablets cent and not more than 101.0 per cent of CI3H22N206S,
calculated on the dried basis.
Neostigmine Bromide Tablets contain not less than 92.5 per
cent and not more than 107.5 per cent of the stated amount of Category. Anticholinesterase.
neostigmine bromide, CI2H,9BrN202.
Dose. By subcutaneous or intramuscular injection, 1 to 2.5
Usualstrength. 15 mg. mg, repeated at suitable intervals; total daily dose,S to 20 mg.

Identification Description. Colourless crystals or a white, crystalline powder;


hygroscopic.
Triturate a quantity of the powdered tablets containing about
0.3 g of Neostigmine Bromide with three quantities, each of Identification
5 ml of ether and discard the ether. Macerate the residue with Test A may be omitted iftests B, C andD are carried out. Tests
several quantities, each of 10 ml of ethanol (95 per cent), B, C and D may be omitted if test A is carried out.
filtering after each maceration. Evaporate the combined filtrates
on a water-bath and dry the residue at 105° for 1 hour. The A. Detennine by infrared absorption spectrophotometry (2.4.6).
residue melts at about 167°, with decomposition. The residue Compare the spectrum with that obtained with neostigmine
complies with the following tests. methylsulphate RS or with the reference spectrum of
neostigmine methylsulphate.
A. Wann about 50 mg with 0.4 g ofpotassium hydroxide and
2 ml of ethanol (95 per cent) on a water-bath for 3 minutes, B. When examined in the range 230 nm to 360 nm (2.4.7), a
replacing the evaporated ethanol. Cool, add 2 ml of dilute 0.05 per cent w/v solution in 0.5 M sulphuric acid shows
diazobenzenesulphonic acid solution; an orange-red colour absorption maxima, at about 261 nm and 267 nm. The ratio of
is produced. the absorbance at the maximum at about 267 run to that at the
maximum at261nm is 0.84 to 0.87.
B. Gives the reactions ofbromides (2.3.1).
C. Dissolve 0.1 g in 5 ml of distilled water and add 1 ml of a
Tests 6 per cent w/v solution of barium chloride; no precipitate is
produced. Add 2 ml of hydrochloric acid and heat in a water-
Other tests. Complies with the tests stated under Tablets. bath for 10 minutes; a white precipitate is produced.
Assay. Weigh and powder 20 tablets. Weigh accurately a D. Wann about 50 mg with 0.4 g ofpotassium hydrOXide and
quantity ofthe powder containing about 0.15 g ofNeostigmine 2 ml of ethanol (95 per cent) on a water-bath for 3 minutes,

1767
NEOSTIGMINE METHYLSULPHATE IP 2010

replacing the evaporated ethai1Ol. Cool, add 2 ml of dilute Usualstrengths. 0.5 mgperml; 2.5 mg per ml.
diazobenzenesulphonic acid solution; an orange-red colour
is produced. Identification
Tests A. Dilute, if necessary, a volume of the injection containing
2.5 mg of Neostigmine Methylsulphate to 5 ml with water,
Appearance ofsolution. A 5.0 per cent w/v solution in distilled shake with three quantities, each of 10 ml, of ether and discard
water is clear (2.4.1), and colourless (2.4.1). the ether extracts.
Acidity or alkalinity. To 4.0ml ofa 5.0 per centw/v solution in When examined in the range 230 urn to 360 urn (2.4.7), a 2 cm
distilled water add 6.0 ml of water and 0.1 ml of phenol- layer of the resulting solution shows absorption maxima at
phthalein solution; the solution is colourless. Add about 260 urn and 267 urn.
0.3 ml of O. 01 M sodium hydroxide; the solution becomes red.
B. Determine by thin-layer chromatography (2.4.17), coating
Add 0.4 ml of 0.01 M hydrochloric acid; the solution becomes
the plate with silica gel G
colourless. Add 0.1 ml of methyl red solution; the solution
becomes red or yellowish-red. Mobile phase. A mixture of 50 volumes of chloroform,
35 volumes of methanol, 10 volumes of formic acid and
3-Hydroxytrimethylanilinium methyl sulphate. Dissolve
5 volumes of water.
50 mg in a mixture of 1 ml of sodium carbonate solution and
9 ml of water. Absorbance of the resulting solution at about Test solution. Dilute the injection under examination, if
294 urn, measured immediately after preparation, not more than necessary, with water to produce a solution containing
0.20(2.4.7). 0.05 per cent w/v ofNeostigmine Methylsulphate.
Chlorides (2.3.12). 1.0 g complies with the limit test for Reference solution (a). A 0.05 per cent w/v solution of
chlorides (250 ppm). neostigmine methylsulphate RS in water.
Sulphates (2.3.17). 0.75 g complies with the limit test for Reference solution (b). A mixture of equal volumes ofthe test
sulphates (200 ppm). solution and reference solution (a).

Loss on drying (2.4.19). Not more than 1.0 per cent, determined Apply to the plate 10 /!l ofeach solution. After development,
on 1.0 g by drying in an oven at 105°. dry the plate in air, spray with dilute potassium
iodobismuthate solution. The principal spot in the
Sulphated ash (2.3.18). Not more than 0.1 per cent. chromatogram obtained with the test solution corresponds to
Assay. Weigh accurately about 0.3 g and dissolve in 150 m1 of that in the chromatogram obtained with reference solution (a).
water. Add 100 ml of2 M sodium hydroxide, distill and collect The principal spot in the chromatogram obtained with
the distillate in 50 ml ofa 4 per cent w/v solution of boric acid reference solution (b) appears as a single, compact spot.
until a total volume of250 ml is reached. Titrate the distillate C. To 1 ml add 0.5 ml of sodium hydroxide solution and
with 0.1 M hydrochloric acid using 0.25 ml of methyl red- evaporate to dryness on a water-bath. Heat quickly in an oil-
methylene blue solution as indicator. Repeat the operation bath to about 250° and maintain at this temperature for about
without the substance under examination. The difference 30 seconds. Cool, dissolve the residue in 1 ml of water, cool in
between the titrations represents the amount of hydrochloric ice water and add 1 ml of diazobenzenesulphonic acid
acid required. solution; an orange-red colour is produced.
1 ml of 0.1 M hydrochloric acid is equivalentto 0.03344 g of
Tests
C13H22N206S.
Storage. Store protected from light and moisture. pH. (2.4.24) 4.5 to 6.5.
3-Hydroxy trimethylanilinium methyl sulphate. Determine
by liquid chromatography (2.4.14).
Test solution. Dilute the injection if necessary, with water to
Neostigmine Injection contain a 0.05 per cent w/v solution of Neostigmine
Neostigmine Methylsulphate Injection Methylsulphate.
Neostigmine Injection is a sterile solution of Neostigmine Reference solution (a). Dilute 1 volume ofthe test solution to
Methylsulphate in Water for Injections. 100 volumes with water.
Neostigmine Injection contains not less than 90.0 per cent Reference solution (b). Add 0.05 ml of5 M sodium hydroxide
and not more than 110.0 per cent of the stated amount of to 1 ml of the test solution and allow to stand for 5 minutes.
neostigmine methylsulphate, C13H22N206S. Add 0.1 ml of 5 M hydrochloric acid and use immediately.

1768
IP 2010 NEOTAME

Chromatographic system Category. Non-nutritive sweetener.


a stainless steel column 25 em x 4.6 rom packed with
Description. A white crystalline powder.
octadecylsilane chemically bonded to porous silica
particles (5 f.!m)(such as Lichrosphere 60 RP-selectB), Identification
mobile phase: 0.0015 M solution of sodium
heptanesulphonate in a mixture of 15 volumes of A. Determine by infrared absorption spectrophotometry
acetonitrile and 85 volumes of 0.05 M potassium (2.4.6). Compare the spectrum with that obtained with neotame
dihydrogen orthophosphate adjusted to pH 3.0 with RS or with the reference spectrum ofneotame.
orthophosphoric acid, B. In the Assay, the principal peak in the chromatogram
flow rate. of 1.1 m1 per minute, obtained with the test solution corresponds to the peak in the
spectrophotometer set at 215 nm, chromatogram obtained with the reference solution.
injection volume. 10 f.!l.
In the chromatogram obtained with reference solution (b) the Tests
principal peak has a retention time of about 6.8 minutes Specific optical rotation (2.4.22). -40° to-43.4°, determined in
(neostigmine methylsulphate) and there is a peak with a a 0.5 per cent w/v solution.
relative retention time of about 0.5 (3-hydroxy)
trimethylani1inium methylsulphate. In the chromatogram Related substances. Determine by liquid chromatography
obtained with the test solution, the area of any secondary (2.4.14).
peak with a retention time corresponding to that ofthe peak Test solution. Dissolve 100 mg ofsubstance under examination
due to (3-hydroxy)trimethylanilinium methylsulphate in the in 50.0 ml ofthe mobile phase.
chromatogram obtained with reference solution (b) is not
Reference solution (a). A 0.002 per cent w/v solution of
greater than the area ofthe principal peak in the chromatogram
neotame RS in the mobile phase.
obtained with reference solution (a) (1 per cent).
Reference solution (b). A 0.003 per cent w/v solution of
Other tests. Complies with the tests stated under Parenteral
neotame impurity A RS in the mobile phase.
Preparations (Injections).
Use the chromatographic system as described under Assay.
Assay. Dilute an accurately measured volume containing about
25 mg ofNeostigmine Methy1sulphate to 50.0 ml with water. Inject reference solution (b). The test is not valid unless the
Measure the absorbance of the resulting solution at the relative standard deviation for replicate injections is not more
maximum at about 260 nm (2.4.7). Calculate the content of than 5.0 per cent.
C 13 H zzNz0 6 S taking 14.35 as the specific absorbance at Inject the test solution and reference solution (a). In the
260nm. chromatogram' obtained with the test solution, the area of
Storage. Store protected from light. peak corresponding to neotame impurity A is not more than
1.5 times the area of the principal peak in the chromatogram
obtained with reference solution (a) (1.5 percent) and the sum
of the areas of all other secondary peaks is not more than
Neotame twice the area of the principal peak in the chromatogram
obtained with reference solution (a) (2.0 per cent).
Loss on ignition (2.4.20). Not more than 0.2 per cent.
Water (2.3.43). NotmorethaiJ. 5.0 per cent, determined on 1.0 g.
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 50 mg ofsubstance under examination
in 25.0 ml ofmobile phase. Dilute 5.0 ml ofthis solution to 10.0
ml with the mobile phase.
Mol.Wt. 378.4
Reference solution. A 0.1 per cent w/v solution ofneotame RS
Neotame isN-(3,3-dimethylbuty1)-L-a-aspartyl-L- in the mobile phase.
phenylalanine 2-methy1 ester.
Chromatographic system
Neotame contains not less than 97.0 per cent and not more - a stainless steel column 10 em x 4.6 mm, packed with
than 102.0 per cent of CzoH30NzOs, calculated on the dried endcapped octadecylsilane bonded to porous silica (5
basis. f.!ID),

1769
NEVlRAPINE IP2010

column temperature. 45°, Test solution. Dissolve 0.1 g of the substance under
mobile phase: dissolve 3 gm of sodium 1- examination in· 100 ml of methanol.
heptanesulphonate and 3.8 ml of tri~thylamine in 750 Reference solution. Dilute 1 ml of the test solution to 100 ml
ml of water, adjust the pH to 3.5 with orthophosphoric
with methanol.
acid. Add 250 ml of acetonitrile, adjust the pH to 3.7
with orthophosphoric acid, Chromatographic system
flow rate. 1.5 ml per minute, a stainless steel column 25 cm x 4.6 mm, packed with
spectrophotometer set at 210 urn, octadecylsilane bonded to porous silica or ceramic
injection volume. 20 Ill. microparticles (5 Ilm),
mobile phase: a filtered and degassed mixture of
Inject the reference solution; The test is not valid unless the 20 volumes of methanol, 20 volumes of acetonitrile
tailing factor is not more than 2.0 and the relative standard and 60 volumes of a buffer prepared by dissolving
deviation for replicate injections is not more than 2.0 per cent. 12.0 g of sodium dihydrogen phosphate in about 800 ml
Inject the test solution and the reference solution. of water, adjusting the pH to 3.0 with phosphoric acid
and diluting to 1000.0 ml with water;
Calculate the content of C2oH30N20s.
- flow rate. 1.2 ml per minute,
Storage. Store protected from moisture. spectrophotometer set at 230 urn,
- injection volume. 20 Ill.
Inject the reference solution. The test is not valid unless the
Nevirapine column efficiency determined from the nevirapine peak is not
less than 5000 theoretical plates and the tailing factor is not
more than 2.0.
Separately inject the test solution and the reference solution.
In the chromatogram obtained with the test solution, the area
of any peak other than the principal peak is not greater than
half of the area of the principal peak in the chromatogram
obtained with the reference solution (0.5 per cent) and the
sum of the areas of all such peaks is not greater than the area
of the principal peak in the chromatogram obtained with the
Mol. Wt. 266.3 reference solution (1.0 per cent).
Nevirapine is ll-cyclopropyl-5,11-dihydro-4-methy-6H- Heavy metals (2.3.13). 1.0 g complies with the limit test for
dipyrido[3,2-b:2' ,3' -e][l,4]diazepin-6-one. heavy metals, Method B (20 ppm).
Nevirapine contains not less than 98.0 per cent and not more Sulphated ash (2.3.18). Not more than 0.2 per cent.
than 102.0 per cent ofClsHl4N40, calculated on the dried basis. Loss on drying (2.4.19). Not more than 0.5 per cent, detennined
Category. Antiretroviral. on 1.0 g by drying at 105° for 3 hours.

Dose. 200 mg once or twice daily. Assay: Determine by liquid chromatography (2.4.14).

Description. A white or almost white crystalline powder. Test solution. A 0.005 per cent w/v solution of the substance
under examination in methanol.
Identification Reference solution. A 0.005 per cent w/v solution of
nevirapine RS in methanol.
A. Determine by infrared absorption spectrophotometry (2.4.6).
Compare the spectrum with that obtained with nevirapine RS Chromatographic system
or with the reference spectrum of nevirapine. - a stainless steel column 25- cm x 4.6 mm, packed with
octadecylsilane bonded to porous silica or ceramic
B. In the Assay, the principal peak in the chromatogram
microparticles (5Ilm),
obtained with the test solution corresponds to that in the
mobile phase: a filtered and degassed mixture of
chromatogram obtained with the reference solution.
20 volumes of methanol, 20 volumes of acetonitrile
Tests and 60 volumes of a buffer prepared by dissolving
12.0 g of sodium dihydrogen phosphate in about 800 ml
Related substances. Determine by liquid chromatography of water, adjusting the pH to 3.0 with orthophosphoric
(2.4.14). acid and diluting to 1000.0 ml with wate/;

1770
IP 2010 NEVIRAPINE ORAL SUSPENSION

flow rate. 1.2 ml per minute, Test solution. To an accurately measured volume of the
spectrophotometer set at 230 urn, preparation under examination containing about 25 mg of
- injection volume. 20 ,.ti. Nevirapine add about 10 ml of methanol, mix with the aid of
Inject the reference solution. The test is not valid unless the ultrasound for 10 minutes, dilute to 50 ml with water, mix and
column efficiency determined from the nevirapine peak is not filter.
less than 3000 theoretical plates, the tailing factor is not more Reference solution. Weigh accurately about 25 mg of
than 2.0 and the relative standard deviation for the replicate nevirapine RS, add about 10 ml of methanol, mix with the aid
injections is not more than 2.0 per cent. of ultrasound to dissolve and dilute to 50 ml with water.
Separately inject the test solution and the reference solution Chromatographic system
and measure the responses for the principal peak. Calculate a stainless steel column 25 cm x 4.6 mm, packed with
the content ofClsHl4N40. octylsilyl silica gel for chromatography (5Ilm) (Such as
Storage. Store protected from moisture. Hypersil C8),
mobile phase: A. 0.1 M ammonium acetate,
B. methanol,
- flow rate. 1 ml per minute,
Nevirapine Oral Suspension a linear gradient programme using the conditions given
below,
Nevirapine Oral Suspension is a suspension ofNevirapine in spectrophotometer set at 270 nm,
a suitable flavoured vehicle. injection volume. 20 ,.ti.
Nevirapine Oral Suspension contains not less than 90.0 per Time Mobile phase A Mobile phase B
cent and not more than 110.0 per cent ofthe stated amount of (in min.) (per cent v/v) (per cent v/v)
nevirapine, ClsH14N40.
o 95 5
Usual strength. 50 mg in 5 ml. 5 95 5
25 20 80
Identification
30 20 80
A. Detennine by thin-layer chromatography (2.4.17), coating 31 95 5
the plate with silica gel GF254. 40 95 5
Mobile phase. A mixture of 40 volumes of 1-butanol, Inject the reference solution. The test is not valid unless the
30 volumes of heptane, 30 volumes of acetone and 10 volumes column efficiency determined from the nevirapine peak is not
of strong ammonia solution. less than 3000 theoretical plates and the tailing factor is not
Test solution. Dilute the preparation under examination with more than 2.0.
methanol to obtain a solution containing 1 mg ofNevirapine Inject separately the diluent (dilute 10 ml of methanol to 50 ml
perml. with water) and the test solution. Examine the diluent
Reference solution. A 0.1 per cent w/v solution of nevirapine chromatogram for any extraneous peaks and ignore the
RS in a mixture of75 volumes of methanol and 25 volumes of corresponding peaks observed in the chromatogram obtained
water. with the test solution. Ignore any peaks due to preservatives
Apply to the plate 10 III of each solution. After development, also.
dry the plate in air and examine in ultraviolet light at 254 urn. Any secondary peak observed in the chromatogram obtained
The principal spot in the chromatogram obtained with the test with the test solution should not be more than 1.0 per cent
solution corresponds to that in the -chromatogram obtained and the sum of the areas of all the secondary peaks should
with the reference solution. not be more than 2.0 per cent when calculated by percentage
B. In the Assay, the principal peak in the chromatogram area normalisation.
obtained with the test solution corresponds to the peak in the Other tests. Comply with the tests stated under Oral Liquids.
chromatogram obtained with the reference solution. Assay. Detennine by liquid chromatography (2.4.14).
Tests Test solution. Weigh accurately a quantity of the preparation
under examination containing 25 mg ofNevirapine, add abol1t
pH (2.4.24). 5.0to 7.0.
10 ml ofmethanol, mix with the aid ofultrasound for 10 minutes,
Related substances. Determine by liquid chromatography dilute to 50.0 ml with water, mix and filter. Further dilute 10.0 ml
(2.4.14). ofthe :filtrate to 25.0 ml with water.

1771
NEVIRAPINE TABLETS IP 2010

Reference solution. Weigh accurately about 50 mg of containing 0.05 per cent w/v ofNevirapine and filter through
nevirapine RS, add about 20 ml ofmethanol, mix with the aid a membrane filter disc with an average diameter not exceeding
of ultrasound to dissolve and dilute to 100.0 ml with water. 1.0 /lm, rejecting the first few ml ofthe filtrate.
Dilute 10.0 ml ofthis solution to 25.0 ml with water.
Reference solution. A 0.05 per cent w/v solution ofnevirapine
Use the chromatographic system described under the test for RS in the mobile phase.
Related substances.
Chromatographic system
Inject the reference solution. The test is not valid unless the a stainless steel column 25 cm x 4.6 mm, packed with
relative standard deviation for replicate injections is not more octadecylsi1ane bonded to porous silica or ceramic
than 2.0 per cent. microparticles (5/lm),
mobile phase: a filtered and degassed mixture of
Inject separately the test solution and the reference solution
20 volumes of methanol, 20 volumes of acetonitrile
and measure the responses for the princip~l peak.
and 60 volumes of a buffer prepared by dissolving
Determine the weight per ml of the oral suspension (2.4.29) 12.0 g ofsodium dihydrogen phosphate in about 800 ml
and calculate the content of CIsHI4N40 weight in volume. of water, adjusting the pH to 3.0 with orthophosphoric
Storage. Store protected from light. acid and diluting to 1000.0 ml with water;
flow rate. 1.2 ml per minute,
spectrophotometer set at 230 nm,
injection volume. 20 Ill.
Nevirapine Tablets Inject the reference solution. The test is not valid unless the
Nevirapine Tablets contain not less than 90.0 per cent and not column efficiency determined from the nevirapine peak is not
more than 110.0 per cent of the stated amount ofnevirapine, less than 7500 theoretical plates and the tailing factor is not
ClsH14N40. more than 1.5 and the relative standard deviation for replicate
injections is not more than 2 per cent.
Usual strength. 200 mg.
Inject the test solution and continue the chromatography for
Identification at least five times the retention time of the principal peak.
A. When examined in the range 200 urn to 400 nm (2.4.7) a Determine the amount of related substances by the area
0.001 per cent w/v solution in the mobile phase described normalisation method. Any individual impurity is not more
under Assay, shows an absorption maximum at about 230 urn. than 1.0 per cent and the sum ofall impurities is not more than
2.0 per cent.
B. In the Assay, the principal peak in the chromatogram
obtained with the test solution corresponds to the peak in the Other tests. Comply with the tests stated under Tablets.
chromatogram obtained with the reference solution. Assay. Determine by liquid chromatography (2.4.14).
Dissolution (2.5.2). Test solution. Weigh and powder 20 tablets. Shake a quantity
Apparatus No.1, of powder containing about 100 mg of Nevirapine with
Medium. 900 ml of 0.1 M hydrochloric acid, . sufficient of the mobile phase to obtain a mixture containing
Speed and time. 50 rpm and 45 minutes. 0.05 per cent w/v of Nevirapine. Mix and filter through a
membrane filter disc with an average pore diameter not greater
Withdraw a suitable volume of the medium and filter through
than 1.0 /lm, rejecting the first few ml ofthe filtrate.
a membrane filter disc with an average pore diameter not greater
than 1.0 /lm, rejecting the first few ml of the filtrate. Dilute Reference solution. A 0.05 per cent w/v solution ofnevirapine
suitably, ifnecessary. Measure the absorbance ofthe resulting RS in the mobile phase.
solution, at the maximum at about 313 urn (2.4.7). Chromatographic system
Calculate the content of CIsHI4N40 from the absorbance a stainless steel column 25 cm x 4.6 mm, packed with
obtained from a solution ofknown concentration ofnevirapine octadecylsilane bonded to porous silica or ceramic
RS in 0.1 M hydrochloric acid. microparticles (5 /lm),
D. Not less than 70 per cent ofthe stated amount ofC,sH'4N40. mobile phase: a filtered and degassed mixture of
20 volumes of methanol, 20 volumes of acetonitrile
Related substances. Determine by liquid chromatography and 60 volumes of a buffer prepared by dissolving
(2.4.14). 12.0 g ofsodium dihydrogen phosphate in about 800 ml
Test solution. Shake a quantity ofthe powdered tablets with a of water, adjusting the pH to 3.0 with phosphoric acid
suitable quantity of the mobile phase to obtain a mixture and diluting to 1000.0 ml with water;

1772
IP 2010 NICLOSAMIDE

flow rate. 1.2 ml per minute, cent w/v solution of ammonium sulphamate, shake, allow to
- spectrophotometer set at 230 nm, stand for 3 minutes and add 2 ml ofa 0.5 per cent w/v solution
injection volume. 20 Ill. ofN-(l-naphthyl) ethylenediamine dihydrochloride; a violet
colour is produced.
Inject the reference solution. The test is not valid unless the
column efficiency determined from the nevirapine peak is not C. Heat the substance under examination on a copper wire in
less than 7500 theoretical plates, the tailing factor is not more a non-luminous flame; a green colour is imparted to the flame.
than 1.5 and the relative standard deviation for replicate
injections is not more than 2.0 per cent. Tests
Separately inject the test solution and the reference solution Related substances. Determine by liquid chromatography
and measure the responses for the principal peale Calculate (2.4.14).
the content ofCIsHI4N40 in the tablets. .
Test solution. Dissolve 50 mg of the substance under
Storage. Store protected from moisture at a temperature not examination in 50 ml ofthe methanol.
exceeding 30°.
Reference solution. Dilute 1.0 ml ofthe test solution to 100.0
ml with acetonitrile. Dilute 1.0 ml of this solution to 20.0 ml
with acetonitrile.
Niclosamide Chromatographic system
Anhydrous Niclosamide - a stainless steel column 12.5 cm x 4.0 mm, packed with
octadecylsilane bonded to porous silica (5 Ilm),
mobile phase: a mixture of 50 volumes of acetonitrile,

~~xrN02
50 volumes ofa solution containing 0.2 per cent w/v of
potassium dihydrogen orthophosphate, 0.1 per cent

yH CI
w/v of disodium hydrogen phosphate and 0.2 per cent
w/v of tetrabutylammonium hydrogen sulphate,
flow rate. 1 ml per minute,
spectrophotometer set at 230 nm,
- injection volume. 20 Ill.
Mol. Wt. 327.1 Inject the reference solution. Adjust the sensitivity so that
Niclosamide is 2' ,5-dichloro-4' -nitrosalicylanilide. the height of the principal peak is not less than 20 per cent of
full scale ofthe recorder.
Niclosamide contains not less than 98.0 per cent and not more
than 101.0 per cent ofC 13H gChNz0 4, calculated on the dried Inject the test solution and the reference solution. Run the
basis. chromatogram twice the retention time of the principal peak.
In the chromatogram obtained with the test solution, the sum
Category. Anthelmintic. ofthe areas ofall the secondary peaks is not more than 4 times
Dose. 2 g as a single dose after a light breakfast followed by a the area of the principle peak in the chromatogram obtained
purgative 2 hours later. with the reference solution. Ignore any peak with an area less
than 10 per cent of the area of the principal peak in the
Description. A yellowish white to yellowish, fine crystals or
chromatogram obtained with the reference solution.
powder; odourless.
Chlorides (2.3.12). T02.0 g add a mixture of40 ml of water and
Identification 1.2 ml of 5 M acetic acid, boil for 2 minutes, cool and filter;
10 ml ofthe filtrate diluted to 15 ml with water complies with
Test A may be omitted if tests Band C are carried out. Tests B
the limit test for chlorides (500 ppm).
and C may be omitted if test A is carried out.
2-Chloro-4-nitroaniline. Not more than 100 ppm, determined
A. Determine by infrared absorption spectrophotometry (2.4.6). by the following method. Boil 0.25 g with 5 ml of methanol,
Compare the spectrum with that obtained with niclosamide cool, add 45 ml of 1 M hydrochloric acid, heat to boiling,
RS or with the reference spectrum of nic1osamide.
coot filter and dilute the filtrate to 50.0 ml with 1 M
B. Heat 50 mg with 5 ml of 1 Mhydrochloric acid and 0.1 g of hydrochloric acid. To 10.0 ml ofthis solution add 0.5 ml of a
zinc powder in a water-bath for 10 minutes, cool and filter. To 0.5 per cent w/v solution of sodium nitrite and allow to stand
the filtrate add 1 ml of a 0.5 per cent w/v solution of sodium for 3 minutes. Add 1.0 ml of a 2 per cent w/v solution of
nitrite and allow to stand for 3 minutes. Add 2 ml of a 2 per ammonium sulphamate, shake, allow to stand for 3 minutes

1773
NICLOSAMIDE IP 2010

and add 1.0 ml ofa 0.5 per cent w/v solution ofN-(I-naphthyij B. Heat 50 mg with 5 ml of 1 Mhydrochlodc acid and 0.1 g of
ethylenediamine dihydrochloride. Any.pinldsh violet colour zinc powder in a water-bath for 10 minutes, cool and filter. To
produced is not more intense than that obtained in a solution the filtrate add 1 ml of a 0.5 per cent w/v solution of sodium
prepared at the same time and in the same manner using nitrite and. allow to stand for 3 minutes. Add 2 ml of a 2 per
10.0 ml of a solution prepared by diluting 2.0 ml of a cent w/v solution of ammonium sulphamate, shake, allow to
0.00050 per cent w/v solution of 2-chloro-4-nitroaniline in stand for 3 minutes apd add 2 ml of a 0.5 per cent w/v solution
methanol to 20 ml with 1 M hydrochloric acid and beginning ofN- (I-naphthyl) ethylenediamine dihydrochloride; a violet
at the words "add 0.5 ml of a 0.5 per cent w/v solution of colour is produced.
sodium nitrite.....".
Tests
5-Chlorosalicylic acid. Not more than 60 ppm, detenniiled by
the following method. Boil 1.0 g with 15 ml of water for Related substances. Detennine by liquid chromatography
2 minutes, cool, filter through a membrane filter (pore size (2.4.14).
0.45 !lm), wash the filter and dilute the combined filtrate and
Test solution. Shake a quantity of the powdered tablets
washings to 20 ml with water: (solution A). Dissolve 30 mg of
containing about 100 mg ofanhydrous nicolsamide with 80 ml
5-chlorosalicylic acid in20 ml of methanol and add sufficient
of methanol for 15 minutes and dilute to 100.0 ml with the
water to produce 100.0 ml. Dilute 1.0 ml of this solution to
same solvent.
100.0 ml with water (solution B). To 10.0 ml ofeach ofsolutions
A and B add separately 0.1 ml offerrie chloride solution; any Reference solution. Dilute 1.0 ml ofthe test solution to 100.0
violet colour produced in solution A is not more intense than ml with acetonitrile and further dilute 1.0 ml ofthis solution to
that obtained in solution B. 20.0 ml with acetonitrile.
Sulphated ash (2.3.18). Not more than 0.1 per cent. Chromatographic system
a stainless steel column 10 cm x 4.6 mm, packed with
Loss on drying (2.4.19). Not more than 0.5 per cent, detennined
octadecylsilane bonded to porous silica (5 !lm) ,
on 1.0 g by drying in an oven at 105° for 4 hours.
- mobile phase: a mixture of 50 volumes of acetonitrile
Assay. Weigh accurately about 0.3 g, dissolve in 80 ml of a and 50 volumes ofa solution containing about 0.2 per
mixture of equal volumes of acetone and methanol. Titrate cent w/v ofpotassium dihydrogen orthophosphate, 0.2
with 0.1 M tetrabutylammonium hydroxide, determining the per cent w/v of tetrabutylammonium hydrogen sulphate
end-point potentiometrically (2.4.25). Carry out a blank titration. and 0.1 per cent w/v of disodium hydrogen
1 ml of 0.1 M tetrabutylammonium hydroxide is equivalent to orthophosphate,
flow rate. I ml per minute,
0.03271 gofCl3HsChN204'
spectrophotometer set at 230 nm,
Storage. Store protected from light and moisture. injection volume. 20 Ill.
Inject the reference solution. Adjust the sensitivity so that
the height of the principal peak is not less than 20 per cent of
full scale of the recorder.
Niclosainide Tablets
Inject the test solution and the reference solution. Run the
Niclosamide Tablets contain not less than 95.0 per cent and chromatogram twice the retention time of the principal peak.
not more than 105.0 per cent of the stated amount of In the chromatogram obtained with the test solution, the sum
niclosamide, C13HsC12N204' The tablets may contain ofthe areas of all the secondary peaks is not more than 4 times
sweetening and flavouring agents. the area of the principle peak in the chromatogram obtained
Usual strength. 500 mg. with the reference solution. Ignore any peak with an area less
than 10 per cent of the area of the principal peak in the
Identification chromatogram obtained with the reference solution.
2-Chloro-4-nitroaniline. Not more than 100 ppm, Boil a
Heat a quantity of the powdered tablets containing 0.5 g of
quantity of the powdered tablets containing 0.1 g of
Niclosamide with 25 ml of hot ethanol (95 per cent), filter
Niclosamide with 20 ml of methanol and 20 ml ofa solution in
while hot and evaporate the filtrate to dryness on a water-
methanol containing 10 !lg of 2-chloro-4-nitroaniline, cool,
bath. The residue complies with the following tests.
add 45 ml of 1 M hydrochloric acid, heat to boiling, cool, filter
A. Detennine by infrared absorption spectrophotomeuy (2.4.6). and dilute the filtrate to 50.0 ml with 1 M hydrochloric acid.
Compare the spectrum with that obtained with niclosamide To 10.0 ml of this solution add 0.5 ml of a 0.5 per cent w/v
RS or with the reference spectrum of niclosamide. solution of sodium nitrite and allow to stand for 3 minutes.

1774
IP 2010 NICOTINAMIDE

Add 1.0 ml of a 2 per cent w/v solution of ammonium Identification


sulphamate, shake, allow to stand for 3 minutes and add
Test A may be omitted iftests B, C andD are carried out. Tests
1.0 ml of a' 0.5 per cent w/v solution of N-(l-naphthyl)
ethylenediamine dihydrochloriqe. Any pinkish violet colour B, C and D may be omitted if test A is carried out.
produced is not more intense than that obtained in a solution A. Determine by infrared absorption spectrophotometry (2.4.6).
prepared at the same time and in the same manner using Compare the spectrum with that obtained with nicotinamide
10.0 ml ofa solution prepared by diluting 2.0 ml ofa 0.0005 per RS or with the reference spectnllTI of nicotinamide.
cent w/v solution of 2-chloro-4-nitroaniline in methanol to
B. Heat about 5 mg in a dry tube; pyridine is evolved.
20.0 ml with 1 M hydrochloric acid and beginning at the
words "add 0.5 ml of a 0.5 per cent w/v solution of sodium C. Boil 0.1 g with 1 ml of dilute sodium hydroxide solution;
nitrite.....". ammonia is evolved.
5-ChlorosaUcyUc acid. Boil a quantity ofthe powdered tablets D. To 2 ml ofa 0.1 per cent w/v solution add 6 ml of cyanogen
containing 0.5 g of Niclosamide with 10 ml of water for bromide solution and I ml of a 2.5 per cent w/v solution of
2 minutes, cool, filter and to the filtrate add 0.2 ml offerric aniline; a golden yellow colour develops.
chloride solution; no red or violet colour is produced.
Tests
Other tests. Comply with the tests stated under Tablets.
Appearance of solution. A 5.0 per cent w/v solution in carbon
Assay. Weigh and powder 20 tablets. Weigh accurately a dioxide-fi-ee water is clear (2.4.1), and not more intensely
quantity of the powdered tablets containing about 0.3 g of coloured than reference solution BYS7 (2.4.1).
Niclosamide dissolved in 60 ml of dimethylformamide. Titrate
pH(2.4.24). 6.0 to 7.5, determined in a 5.0 per centw/v solution.
with 0.1 M teirabutylammonium hydroxide, determining the
end-point potentiometrically (2.4.25). Carry out a blank titration. Related substances. Determine by thin-layer chromatography
(2.4.17), coating the plate with silica gel GF254.
1 ml of 0.1 M tetrabutylammonium hydroxide is equivalent to
0.03271 gofC13HsC12N204' Mobile phase. A mixture of 48 volumes of chloroform,
45 volumes of ethanol and 4 volumes of water.
Storage. Store protected from light and moisture.
Test solution. Dissolve 0.8 g of the substance under
Labelling. The label states that the tablets should be chewed
examination in 10 ml of ethanol (50 per cent).
thoroughly before swallowing.
Reference solution. A 0.02 per cent w/v solution of the
substance under examination in ethanol (50 per cent).
Apply to the plate 5 f..ll of each solution. Allow the mobile
Nicotinamide phase to rise 10 cm. Dry the plate in air and examine in ultraviolet
Niacinamide light at 254 mTI. Any secondary spot in the chromatogram
obtained with the test solution is not more intense than the
N spot in the chromatogram obtained with the reference solution.

OyNH 2
Heavy metals (2.3.13). Dissolve 0.67 gin 10 mlofwater, 7.5 ml
of 1 M hydrochloric acid and sufficient water to produce
o 25 ml. The solution complies with the limit test for heavy metals,
Method A (30 ppm).
C6H6N 20 Mol. Wt. 122.1
Chlorides (2.3.12). 1.0 g complies with the limit test for
Nicotinamide ispyridine-3-carboxamide. chlorides (250 ppm).

Nicotinamide contains not less than 99.0 per cent and not Sulphates (2.3.17). 1.2 g complies with the limit test for
more than 101.0 per cent ofC6H6N 20, calculated on the dried sulphates (125 ppm).
basis. Sulphated ash (2.3.18). Not more than 0.1 per cent.

Category. B-group vitamin. Loss on drying (2.4.19). Not more than 0.5 per cent, determined
on 1.0 g by drying over phosphorus pentoxide at a pressure
Dose. Orally, prophylactic, 15 to 30 mg daily; therapeutic, 50 of 1.5 to 2.7 kPa for 18 hours.
to 250 mg daily. By intravenous injection, .50 to 250 mg daily.
Assay. Weigh accurately about 0.25 g, dissolve in 20 ml of
DescriptioR Colourless crystals or a white, crystalline powder; anhydrous glacial acetic acid, heating slightly if necessary.
odour, faint and characteristic. Add 5 ml of acetic anhydride. Titrate with 0.1 M perchloric

1775
NICOTINAMIDE TABLETS IP 2010

acid, using crystal violet solution as indicator. Carry out a light at 254 urn. Any secondary spot in the chromatogram
blank titration. obtained with the test solution is not more intense than the
spot in the chromatogram obtained with the reference solution.
I ml of 0.1 M perchloric acid is equivalent to 0.01221 g of
C6H6NzO. Other tests. Comply with the tests stated under Tablets.
Storage. Store protected from moisture. Assay. Weigh and powder 20 tablets. Weigh. accurately a
quantity of the powder containing about 50 mg of
Nicotinamide, shake with 50 ml of ethanol (95 per cent) for 15
minutes and dilute to 100.0 ml with ethanol (95 per cent). Mix,
Nicotinamide Tablets filter, dilute 5.0 ml ofthe filtrate to 100.0 ml with ethanol (95
Niacinamide Tablets per cent) and measure the absorbance ofthe resulting solution
at the maximum at about 262 nm (2.4.7). Calculate the content
Nicotinamide Tablets contain not less than 92.5 per cent and of C6H 6N zO taking 241 as the specific absorbance at 262 nm.
not more than 107.5 per cent of the stated amount of
nicotinamide, C6H 6N zO. Storage. Store protected from light and moisture.

Usual strength. 50 mg.

Identification Nicotinic Acid


Shake a quantity of the powdered tablets containing 0.2 g of Niacin
Nicotinamide with 50 ml of ethanol for 15 minutes, filter and
evaporate the filtrate to dryness on a water-bath. The residue N
complies with the following tests. ~")
A. Determine by infrared absorption spectrophotometry (2.4.6). ~COOH
Compare the spectrum with that obtained with nicotinamide
RS or with the reference spectrum of nicotinamide. C6HsNOz Mol. Wt. 123.1

B. Boil 0.1 g with I ml of dilute sodium hydroxide solution; Nicotinic Acid is pyridine-3-carboxylic acid.
ammonia is evolved. Nicotinic Acid contains not less than 99.5 per cent and not
C. To 2 ml ofa 0.1 per cent w/v solution add 6 ml of cyanogen more than 100.5 per cent ofC 6H sNOz, calculated on the dried
bromide solution and 1 ml of a 2.5 per cent w/v solution of basis.
aniline; a golden yellow colour develops. Category. B-group vitamin.
D. When examined in the range 230 nm to 360 nm (2.4.7), the Dose. Prophylactic, 15 to 30 mg daily; therapeutic, 50 to 250
solution obtained in the Assay shows an absorption maximum mgdaily.
only at about 262 nm and two shoulders at about 258 urn and
Description. A white or creamy-white, crystalline powder.
269nm.

Tests Identification
Related substances. Determine by thin-layer chromatography Test A may be omitted iftests B, C andD are carried out. Tests
(2.4.17), coating the plate with silica gel GF254. B, C and D may be omitted if test A is carried out.
Mobile phase. A mixture of 48 volumes of chloroform, A. Determine by infrared absorption spectrophotometry (2.4.6).
45 volumes of ethanol and 4 volumes of water. Compare the spectrum with that obtained with nicotinic acid
RS or with the reference spectrum of nicotinic acid.
Test solution. Shake a quantity of the powdered tablets
containing 0.1 g of Nicotinamide with 15 ml of ethanol for B. Heat a small quantity with twice its weight of soda lime;
15 minutes, filter, evaporate to dryness on a water-bath and pyridine is evolved.
dissolve the residue as completely as possible in 1 ml of C. Dissolve about 50 mg in 20 ml of water, neutralise to litmus
ethanol. paper with 0.1 M sodium hydroxide, add 3 ml of copper
Reference solution. Dilute 1 volume of the test solution to sulphate solution; a blue precipitate is gradually produced.
400 volumes with ethanol D. To 2 ml ofa 0.1 per cent w/v solution add 6 ml of cyanogen
Apply to the plate 5 III of each solution. Allow the mobile bromide solution and I ml of a 2.5 per cent w/v solution of
phase to rise 10 cm. Dry the plate in air and examine in ultraviolet aniline; a golden yellow colour is produced.

1776
IP 2010 NICOUMALONE

Tests Test solution. Shake a quantity of the powdered tablets


containing 50 mg ofNicotinic Acid with 50 ml of hot ethanol
Related substances. Determine by thin-layer chromatography
(95 per cent), filter and allow the filtrate to cool.
(2.4.17), coating the plate with silica gel GF254.
Mobile phase. A mixture of 85 volumes of I-propanol, Reference solution. A 0.1 per cent w/v solution of nicotinic
10 volumes of anhydrousformic acid and 5 volumes of water.
acid RS in ethanol (95 per cent).

Test solution. Dissolve 0.2 g of the substance under Apply to the plate 5 !!l of each solution. After development,
examination in 10 ml of water. Warm slightly, ifnecessary. dry the plate in air and examine in ultraviolet light at 254 om.
The principal spot in the chromatogram obtained with the test
Reference solution. A 0.01 per cent w/v solution of the
solution corresponds to that in the chromatogram obtained
substance under examination in water.
with the reference solution.
Apply to the plate 5 !!l of each solution. After development,
B. Triturate a quantity of the powdered tablets containing
dry the plate at 105° for 10 minutes and examine in ultraviolet
50 mg ofNicotinic Acid with 10 ml of water and filter. To 2 ml
light at 254 nm. Any secondary spot in the chromatogram
ofthe filtrate add 6 ml of cyanogen bromide solution and 1 ml
obtained with the test solution is not more intense than the
of a 2.5 per cent w/v solution of aniline; a golden yellow
spot in the chromatogram obtained with the reference solution.
precipitate is produced.
Heavy metals (2.3.13). Mix 1.0 g with 1.5 ml of dilute
hydrochloric acid and sufficient water to produce 25 ml, heat C. Shake a quantity of the powdered tablets containing 0.1 g
gently and cool to room temperature. The resulting solution of Nicotinic Acid with ethanol (95 per cent), filter and
complies with the limit test for heavy metals, Method B evaporate the filtrate to dryness. Add to the residue 10 mg of
(20 ppm). citric acid and 0.15 ml of acetic anhydride and heat on a
water-bath; a reddish-violet colour is produced.
Chlorides (2.3.12). 1.0 g complies with the limit test for
chlorides (250 ppm). Tests
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Other tests. Comply with the tests stated under Tablets.
Loss on drying (2.4.19). Not more than 1.0 per cent, determined
on 1.0 g by drying in an oven at 105° for 1 hour. Assay. Weigh and powder 20 tablets. Weigh accurately a
quantity of the powder containing about 0.25 g of Nicotinic
Assay. Weigh accurately about 0.25 g, dissolve in 50 ml of Acid, add 40 ml of hot ethanol (95 per cent), previously
carbon dioxide-free water and titrate with 0.1 M sodium neutralised to phenolphthalein solution, and shake. Allow to
hydroxide using phenol red solution as indicator. Repeat the stand for 15 minutes, swirling occasionally, and then shake
operation without the substance under examination. The for 10 minutes. Filter through a plug of cotton and wash the
difference between the titrations represents the amount of filter with ethanol (95 per cent). Add 50 ml of carbon dioxide-
sodium hydroxide required. free water and titrate with 0.1 M sodium hydroxide using
1 ml of 0.1 M sodium hydroxide is equivalent to 0.01231 g of phenol red solittion as indicator.
C6H sNOz.
1 ml of 0.1 M sodiilm hydroxide is equivalent to 0.01231 g of
Storage. Store protected from light and moisture. C6H sNO z. '
Storage. Store protected from light and moisture.

Nicotinic Acid Tablets


Niacin Tablets Nicoumalone
Nicotinic Acid Tablets contain not less than 92.5 per cent and
Acenocoumarol
not more than 107.5 per cent ofthe stated amount ofnicotinic
acid, C6H sNO z.
NOz
Usual strengths. 25 mg; 50 mg; 100mg.
Identification
A. Determine by thin-layer chromatography (2.4.17), coating
the plate with silica gel GF254.
Mobile phase. A mixture of 48 volumes of chloroform,
45 volumes of ethanol (95 per cent) and 8 volumes of water. CI9HISN06
° Mol. Wt. 353.3

1777
NICOUMALONE IP 2010

Nicoumalone is (RS)-4-hydroxy-3-[ 1-(4-nitrophenyl)-3- Sulphated ash (2.3.18). Not more than 0.1 per cent.
oxobutyl]coumarin.
Loss on drying (2.4.19). Not more than 0.5 per cent; determined
Nicoumalone contains not less than 98.5 per cent and not on 1.0 g by dIying in an oven at 105°.
more than 100.5 percent ofC19HlsN06, calculated on the dried
Assay. Weigh accurately about 0.75 g, dissolve in 50 ml of
basis.
acetone and titrate with 0.1 M sodium hydroxide using
Category. Anticoagulant. bromothymol blue solution as indicator.. Repeat the operation
without the substance under examination. The difference
Dose. Initial dose, first day, 8 to 12 mg; second day, 4 to 8 mg;
between the titrations represents the amount of sodium
maintenance dose, 1 to 8 mg daily.
hydroxide required.
Description. A white to brownish-white powder; odourless or
1 ml of 0.1 M sodium hydroxide is equivalent to 0.03533 g of
almost odourless.
C19HlsN06.

Identification Storage. Store protected from light.

A. Determine by infrared absorption spectrophotometry (2.4.6).


Compare the spectrum with that obtained with nicoumalone
RS or with the reference spectrum of nicoumalone.

B. When examined in the range 230 nm to 360 nm (2.4.7), a


Nicoumalone Tablets
0.001 per cent w/v solution in a mixture of 9 volumes of Acenocoumarol Tablets
methanol and 1 volume of 1 M hydrochloric acid shows
absorption maxima at about 283 mn and 306 nm; absorbances Nicoumalone Tablets contain not less than 90.0 per cent and
at the maxima, about 0.65 and about 0.52, respectively. not more than 110.0 per cent of the stated amount of
nicoumalone, C19HlsN06.
C. Heat 50 mg with 2.5 ml of glacial acetic acid, 0.5 ml of
Usual strengths. 1 mg; 2 mg; 3 mg; 4 mg.
hydrochloric acid and 0.2 g of zinc powder on a water-bath
for 5 minutes, cool and filter. To the filtrate add 0.05 ml of
sodium nitrite solution and add the mixture to 10 ml ofa·l per Identification
cent wlvsolution of 2-naphthol containing 3 ml of5 M sodium
A. Heat a quantity of the powdered tablets containing 50 mg
hydroxide; a bright red precipitate is produced.
ofNicoumalone with 30 ml of acetone under a reflux condenser
Tests for 5 minutes, filter and wash the residue with two quantities,
each of 10 ml, of acetone. Evaporate the combined filtrate and
Appearance of solution. A 2.0 per centw/v solution in acetone washings to 5 ml, add water dropwise until the solution
is clear (2.4.1). » becomes turbid, heat on a water-bath until the solution is
clear and allow to stand. Filter, wash the crystals with a mixture
B. A 2.0 per cent w/v solution in 0.1 M sodium hydroxide is
of equal volumes of acetone and water and dry at 100° at a
clear (2.4.1), and yellow.
pressure of2 kPa for 30 minutes.
Related substances. Determine by thin-layer chromatography
(2.4.17), coating the plate with silica gel GF254. On the residue determine by infrared absorption
spectrophotometry (2.4.6). Compare the spectrum with that
Mobile phase. A mixture of 50 volumes of chloroform, obtained with nicoumalone RS or with the reference spectrum
50 volumes of cyclohexane and 20 volumes of glacial acetic ofnicoumalone.
acid.
B. When examined in the range 230 nm to 360 nm (2.4.7), the
Test solution. Dissolve 0.2 g of the substance under final solution obtained in the Assay shows absorption maxima
examination in 10 ml of acetone. at about 283 nm and 306 nm.
Reference solution. A 0.002 per cent w/v solution of the C. Heat 50 mg ofthe residue obtained in testA, with 2.5 ml of
substance under examination in acetone.
glacial acetic acid, 0.5 ml of hydrochloric acid and 0.2 g of
Apply to the plate 20 J.ll of each solution. After development, zinc powder on a water-bath for 5 minutes, cool and filter. To
illy the plate in air and irmnediately examine in ultraviolet light the filtrate add 0.05 ml of sodium nitrite solution and add the
at 254 nm. Any secondary spot in the chromatogram obtained mixture to 10 ml of a 1 per cent w/v solution of 2-naphthol
with the test solution is not more intense than the spot in the containing 3 ml of 5 M sodium hydroxide; a bright red
chromatogram obtained with the reference solution. precipitate is produced.

1778
IP 2010 NIFEDIPINE

Tests Nifedipine
Related substances. Detennine by thin-layer chromatography
(2.4.17), coating the plate with silica gel GF254.

Mobile phase. A mixture of 50 volumes of chloroform,


50 volumes of cyclohexane and 20 volumes of glacial acetic OCH 3
acid.
o
Test solution. Shake a quantity of the powdered tablets
containing 20 mg of Nicoumalone with 5 ml of acetone,
centrifuge and use the supernatant liquid.

Reference solution. Dilute 1 volume of the test solution to C17HISN206 Mol. Wt. 346.3
200 volumes with acetone.
Nifedipine is dimethyll,4-dihydro-2,6-dimethyl-4-(2-
Apply to the plate 20 J1.1 of each solution. After development, nitrophenyl)pyridine-3,5-dicarboxylate. .
dry the plate in air and immediately examine in ultraviolet light Nifedipine contains not less than 98.0 per cent and not more
at 254 nm. Any secondary spot in the chromatogram obtained than 102.0 per cent of CI7HISN206, calculated on the dried
with the test solution is not more intense than the spot in the basis.
chromatogram obtained with the reference solution.
Category. Antianginal (calcium channel blocker).
Uniformity of content. Comply with the test stated under
Dose. Initial dose, 5-20 mg daily, in divided doses; subsequent
Tablets.
doses, in accordance with the needs of the patient but total
Finely crush one tablet, add 30 ml of methanol, stir the mixture daily dose not to exceed 100 mg.
for 30 minutes and filter through sintered glass, washing the Description. A yellow, crystalline powder; readily affected by
residue with three quantities, each of 15 ml, of methanol. To exposure to light.
the combined. filtrate and washings add 10 ml of 1 M
hydrochloric acid and sufficient methanol to produce NOTE- Nifedipine, when exposed to daylight and certain
100.0 ml. Ifnecessary, dilute further with a solvent prepared wavelengths of artificial light, readily converts to a
by diluting 1 volume of 1 M hydrochloric acid to 10 volumes nitrosophenyl derivative. Exposure to ultraviolet light leads
with methanol to produce a solution containing about to the formation of a nitrophenyl derivative. Pelform the
0.001 per cent w/v solution of Nicoumalone. Measure the tests and assay in the dark or under long-wavelength light
absorbance ofthe resulting solution at the maximum at about (greater than 420 nm). Use low-actinic glassware.
306 nm (2.4.7). Calculate the content OfC19HlSN06 taking 521
as the specific absorbance at 306 run. Identification
Test A may be omitted iftests B, C and D are carried out. Tests
Other tests. Comply with the tests stated under Tablets.
B, C and D may be omitted iftest A is carried out.
Assay. Weigh and powder 20 tablets. Weigh accurately a A. Detennine by infrared absorption spectrophotometry (2.4.6).
quantity of the powder containing about 10 mg of Compare the spectrum with that obtained with nifedipine RS
Nicoumalone, add 30 ml of methanol, stir the mixture for or with the reference spectrum of nifedipine.
30 minutes and filter through sintered-glass, washIng the .. .
'd .h h .. 1 f 15 1 f h I 'T' B. In the test for Related substances, the pnnclpal peak m the
resl ue WIt tree quantttles, eac 1 0 m , 0 met ana. 10 ." .
· d f'l d l' dd 10 1 f 1 M . chromatogmm obtamed WIth the test solutIon corresponds to
th e com b me I trate an was Hngs a mo.... . .
' 'd d ff" f I d the peak due to mfedlpme 111 the chromatogram obtamed WIth
hy droc hionc aCI an su IClent met tano to pro uce tl fi 1 t'
100.0 ml. Dilute 5.0 ml ofthis solution to 50.0 ml with a solvent le re erence so u Ion (a).
prepared by diluting 1 volume of 1 M hydrochloric acid to C. Detennineby thin-layer chromatography (2.4.17), coating
10 volumes with methanol and measure the absorbance ofthe the plate with silica gel GF254.
resulting solution at the maximum at about 306 nm (2.4.7). Mobile phase. A mixture of 60 volumes of cyclohexane and
Calculate the content ofC19HIsN06 taking 521 as the specific 40 volumes of ethyl acetate.
absorbance at 306 nm.
Test solution. Dissolve 0.1 g of the substance under
Storage. Store protected from light and moishlre. examination in 100 ml of methanol.

1779
NIFEDIPINE IP 2010

Reference solution. A 0.1 per cent w/v solution of nifedipine analogue and nifedipine (retention time about 15.5 minutes).
RS in methanol. The test is not valid unless, in the chromatogram obtained
Apply to the plate 5 !-t1 of each solution. After development, with reference solution (d), (a) the resolution factor between
dry the plate in air and examine in ultraviolet light at 254 urn. the peaks due to the nitrophenylpyridine analogue and the
The principal spot in the chromatogram obtained with the test nitrosophenylpyridine analogue is greater than 1.5, (b) the
solution corresponds to that in the chromatogram obtained resolution between the peaks due to the nitrosophenylpyridine
with the reference solution. analogue and nifedipine is greater than 1.5, and (c) the height
of the peak due to the nitrophenyl-pyridine analogue is at
D. To 25 mg add 10 ml of a mixture of 5 volumes of ethanol least 20 per cent ofthe full-scale deflection.
(95 per cent), 3.5 volumes of water and 1.5 volumes of
hydrochloric acid and dissolve with gentle heating. Add Inject the test solution and reference solutions (a) and (d) and
0.5 g of granulated zinc and allow to stand for 5 minutes, record the chromatograms for twice the retention time of
swirling occasionally. Filter, add 5 ml ofa 1per cent w/v solution nifedipine. In the chromatogram obtained with the test solution
ofsodium nitrite to the filtrate and allow to stand for 2 minutes. no secondary peak other than any peaks corresponding to
Add 2 m1 ofa 5 per cent w/v solution of ammonium sulphamate, the nitrophenylpyridine analogue and the nitrosophenylpyridine
shake vigorously with care and add 2 ml of a 0.5 per cent w/v analogue has an area greater than that of the peak due to
solution ofN-(I- naphthyl) ethylenediamine dihydrochloride; nifedipine in the chromatogram obtained with reference solution
an intense red colour develops which persists for more than (d) and the areas of any peaks corresponding to the
5 minutes. nitrophenylpyridine analogue and the nitrosophenylpyridine
analogue are not greater than the areas of the corresponding
Tests peaks in the chromatogram obtained with reference solution
Related substances. Determine by liquid chromatography (d). The total amount of related substances is not greater than
(2.4.14). 0.3 per cent. Ignore any peak with an area less than 10 per cent
ofthe area ofthe peak due to nifedipine in the chromatogram
Test solution. Dissolve 0.2 g of the substance under obtained with reference solution (d).
examination in 20 ml of methanol and dilute to 50 ml with the
mobile phase. Heavy metals (2.3.13). 2.0 g complies with limittest for heavy
Reference solution (a). Dissolve an accurately weighed metals, Method B (l0 ppm).
quantity of nifedipine RS in sufficient methanol to produce a Sulphated ash (2.3.18). Not more than 0.1 per cent.
1.0 per cent w/v solution and dilute quantitatively with the
mobile phase to obtain a 0.4 per cent w/v solution. Loss on drying (2.4.19). Not more than 0.5 per cent, determined
on 1.0 g by drying in an oven at 105° for 2 hours.
Reference solution (b). A 0.04 per cent w/v solution of
dimethyl-2,6-dimethyl-4-(2-nitrophenyl)pyridine-3, 5- Assay. Weigh accurately about 0.13 g, dissolve in a mixture of
dicaboxylate RS (nitrophenylpyridine analogue) in methanol. 25 ml of 2-methyl-2-propanol and 25 ml of 1 M perchloric
Reference solution (c). A 0.04 per cent w/v solution of acid and titrate with 0.1 M ceric ammonium sulphate, using
dimethyl- 2, 6-dimethyl-4-(2-nitrosophenyl)pyridine-3, 5- 0.1 ml offerroin solution as indicator until the pink colour is
dicarboxylate RS (nitroso- phenylpyridine analogue) in discharged, titrating slowly towards the end-point. Carry out
methanol. a blank titration.

Reference solution (d). Mix 1 volume of each of reference 1 ml of 0.1 M ceric ammonium sulphate is equivalent to
solutions (b) and (c) and 0.1 volume ofthe test solution, dilute 0.01732 g ofCI7HlsN206.
to 10 volumes with the mobile phase and then dilute 2 volumes
Storage. Store protected from light.
ofthe resulting solution to 10 volumes with the mobile phase.
Chromatographic system
- a stainless steel column 15 cm x 4.6 mm, packed with
octadecylsilane bonded to porous silica (5 !-tm), Nifedipine Capsules
- mobile phase: 55 volumes of water, 36 volumes of
Nifedipine Capsules contain not less than 90.0 per cent and
methanol and 9 volumes of acetonitrile,
not more than 110.0 per cent ofthe stated amount ofnifedipine,
- flow rate. 1 ml per minute,
CI7HISN206.
- spectrophotometer set at 235 urn,
injection volume. 20 !-tl. Usualstrengths. 5 mg; 10 mg.
Inject reference solution (d). The peaks appear in the order NOTE - Nifedipine, when exposed to daylight and certain
nitrophenylpyridine analogue, nitrosophenylpyridine wavelengths of artificial light, readily converts to a

1780
IP 2010 NIFEDIPINE SUSTAINED-RELEASE TABLETS

nitrosophenyl derivative. Exposure to ultraviolet light leads with the aid ofsmall quantities of methanol. Dilute to volume
to the formation of a nitrophenyl derivative. Perform the with methanol and mix. To 20.0 ml add sufficient methanol to
tests and assay in the dark or under long-wavelength light produce 100.0 ml and mix. Measure the absorbance of the
(greater than 420 nm). Use low-actinic glassware. resulting solution at the maximum at about 350 nm (2.4.7).
Calculate the content ofC,7H,sN206 in the capsules from the
Identification absorbance obtained by repeating the operation with a
0.005 per cent w/v solution of nifedipine RS in methanol.
Determine by thin-layer chromatography (2.4.17), coating the
plate with silica gel GF254. Storage. Store protected from light.
Mobile phase. A mixture of equal volumes of ethyl acetate
and cyclohexane.
Test solution. Transfer a quantity ofthe contents ofthe capsules Nifedipine Sustained-release Tablets
containing 30 mg of Nifedipine into a centrifuge tube containing
Nifedipine Sustained-release Tablets contain not less than
0.1 M sodium hydroxide, add 25 ml of dichloromethane,
90.0 per cent and not more than 110.0 per cent of the stated
stopper the tube and shake gently for 1 hour. Centrifuge for
amountofnifedipine, CI7HISN206.
10 minutes' at 2000 to 2500 rpm. Remove the supernatant
aqueous layer by aspiration with a syringe and transfer 5 mlof NOTE - Nifedipine, when exposed to daylight and certain
the clarified lower layer to a suitable vial. wavelengths of artifiCial light, readily converts to a
nitrosophenyl derivative. Exposure to ultraviolet light leads
Reference solution (a). A 0.12 per cent w/v solution of
to the formation of a nitrophenyl derivative. Perform the
nifedipine RS in dichloromethane.
tests and the assay in the dark or under long-wavelength
Reference solution (b). A mixture of equal volumes of test light (greater than 420 nm). Use low-actinic glassware.
solution and reference solution (a).
Usualstrengths. 10 mg; 20 mg.
Apply to the plate 500 III ofeach solution as bands 20 mm by
3 mm. After development, dry the plate in air until the solvent Identification
is not detectable and immediately examine in ultraviolet light
at 254 Dm. The principal band, appearing as a dark blue band, Determine by thin-layer chromatography (2.4.17), coating the
in the chromatogram obtained with the test solution plate with silica gel GF254.
corresponds to that in the chromatogram obtained with the Mobile phase. A mixture of equal volumes of ethyl acetate
reference solution (a). Spray with a solution prepared in the and cyclohexane.
following manner. Dissolve 3 g of bismuth subnitrate and 30 g
Test solution. Transfer a quantity of the powdered tablets
of potassium iodide in 10 ml of 3 M hydrochloric acid and
containing 30 mg ofNifedipine into a centrifuge tube containing
dilute with water to 100 m1; dilute 10 ml to 100 ml with 0.3 M
0.1 M sodium hydroxide, add 25 ml of dichloromethane,
hydrochloric acid. In the chromatogram obtained with test
stopper the tube and shake gently for 1 hour. Centrifuge for 10
solution the principal band, appearing as a compact light
minutes at 2000 rpm to 2500 rpm. Remove the supernatant
orange band against a yellow background, corresponds to
aqueous layer by aspiration with a syringe and use 5 ml ofthe
that in the chromatogram obtained with reference solution (a).
clarified lower layer.
The band obtained with reference solution (b) appears as a
single band under both visualisation procedures. Reference solution. A 0.12 per cent w/v solution of nifedipine
RS in dichloromethane.
Tests
Apply to the plate 500 III of each solution as bands 20 mm by
Uniformity of content. Comply with the test stated under 3 mm. After development, dry the plate in air until the odour of
Capsules. the solvent is not detectable and immediately examine in
Transfer the contents of a capsule quantitatively to a 200-ml ultraviolet light at 254 Dm. The principal band, appearing as a
volumetric flask with the aid of methanol, dilute to volume dark blue band, in the chromatogram obtained with the test
with methanol and mix. Complete the Assay beginning at the solution corresponds to that in the chromatogram obtained
words "Measure the absorbance...." and calculate the content with the reference solution. Spray with a solution prepared in
ofC17HlsN206 in the capsule. the following manner. Dissolve 3 g of bismuth subnitrate and
30 g of potassium iodide in 10 ml of 3 M hydrochloric acid
Other tests. Comply with the tests stated under Capsules.
and dilute to 100 ml with water; dilute 10 ml ofthis solution to
Assay. Transfer the contents of 5 capsules containing about 100 ml with 0.3 M hydrochloric acid. In the chromatogram
50 mg ofNifedipine quantitatively to a 200-ml volumetric flask obtained with the test solution the principal band, appearing

1781
NIFEDIPINE SUSTAINED-RELEASE TABLETS IP 2010 .

as a compact light orange band againsta yellow background, Nifedipine Tablets


corresponds to that in the chromatogram obtained with
reference solution. Nifedipine Tablets contain not less than 90.0 per cent anduot
more than 110.0 per cent of the stated amount ofnifedipine,
Tests C17HISNz06' The tablets may be coated.
Usual strengths. 5 mg; 10 mg.
Dissolution (2.5.2).
A. Apparatus No.1,
NOTE - Nifedipine, when exposed to daylight and certain
wavelengths of artificial light, readily converts to a
Medium. 900 ml of 0.1 M hydrochloric acid,
nitrosophenyl derivative. Exposure to ultraviolet light leads
Speed and time. 150 rpm and 120 minutes.
to the formation of a nitrophenyl derivative. Pelform the
Withdraw a suitable volume ofthe medium and filter. Measure tests and assay in the dark or under long-wavelength light
the absorbance of the filtrate, suitably diluted with the (greater than 420 nm). Use low-actinic glassware.
dissolution medium, ifnecessary, at the maximum at about 340
run (2.4.7). Identification

Calculate the content ofC17HlsNz06 in the medium from the Detennine by thin-layer chromatography (2.4.17), coating the
absorbance obtained from a solution oflmown concentration plate with silica gel GF254.
of nifedipine RS prepared by dissolving in minimum volume Mobile phase. A mixture of equal volumes of ethyl acetate
of methanol and then diluting with the dissolution medium. and cyclohexane.
D. Not less than 25 per cent and not more than 45 per cent of Test solution. Transfer a quantity of the powdered tablets
the stated amount of C17HISNz06. containing 30 mg ofNifedipine to a centrifuge tube containing
20 ml of 0.1 M sodium hydroxide, add 25 mlof dichloromethane,
B. Apparatus No.1,
stopper the tube and shake gently for 1 hour. Centrifuge for 10
Medium. 900 ml of phosphate buffer pH 6.8 prepared by minutes at 2000 to 2500 rpm. Remove the supernatant aqueous
dissolving 30 g of sodium lawyl sulphate, 24.8 g of disodium layer by aspiration with a syringe and transfer 5.0 ml of the
hydrogen phosphate anhydrous, 2.85 g of citric acid clarified lower layer to a suitable vial.
monohydrate and 0.75 ml of orthophosphoric acid in sufficient Reference solution (a). A 0.12 per cent w/v solution of
water to produce 6000 ml. Adjust the pH to 6.8, if necessary, nifedipine RS in dichloromethane.
Replace 0.1 M hydrochloric acid with phosphate buffer pH Reference solution (b). A mixture of equal volumes ofthe test
6.8 and run the apparatus at 150 rpm for 6 hours. Withdraw a solution and reference solution (a).
suitable volume of the medium and filter. Measure the
absorbance ofthe filtrate, suitably diluted with the dissolution Apply to the plate 500 f..Ll of each solution as bands 20 mm by
medium, ifneceSSaIy, at the maximum at about 340 nm (2.4.7). 3 mrn. After development, dry the plate in air until the solvent
is not detectable and immediately examine in ultraviolet light
Calculate the content ofC17HlsNz06 in the medium from the at 254 run. The principal band, appearing as a dark blue band,
absorbance obtained from a solution oflmown concentration in the chromatogram obtained with the test solution
of nifedipine RS prepared by dissolving in minimum volume corresponds to that in the chromatogram obtained with
of methanol and then diluting with the dissolution medium. reference solution (a). Spray with a solution prepared in the
D. Not less than 60 per cent of the stated amount of following manner. Dissolve 3 g of bismuth subnitrate and 30 g
C17HISNz06. of potassium iodide in 10 ml of 3 M hydrochloric acid and
dilute with water to 100 ml; dilute 10 ml to 100 ml with 0.3 M
Other tests. Comply with the tests stated under Tablets. hydrochloric acid. In the chromatogram obtained with the
Assay. Weigh and powder 20 tablets. Weigh accurately a test solution the principal band, appearing as a compact light
quantity ofthe powder containing about 25 mg ofNifedipine, orange band against a yellow background, corresponds to
disperse in methanol, shake and dilute to 100.0 ml with that in the chromatogram obtained with reference solution (a).
methanol, filter. Dilute 20.0 ml ofthe filtrate to 100.0 ml with The band obtained with reference solution (b) appears as a
methanol. Measure the absorbance of the resulting solution single band under both visualisation procedures.
at the maximum at about 350 nm (2.4.7). Calculate the content
OfC17HISNz06 from the absorbance obtained with a 0.005 per Tests
cent w/v solution of nifedipine RS in methanol.
Uniformity of content. Comply with the test stated under
Storage. Store protected from light and moisture. Tablets

1782
IP 2010 NIKETHAMIDE

Shake one tablet with methanol in a 200-ml volumetric flask, C. Heat 0.1 g with I ml of 2 M sodium hydroxide; diethylamine,
dilute to volume with methanol, mix and filter. Complete the recognisable by its odour, is evolved progressively; the fumes
Assay beginning at the words "Measure the absorbance...." tum red litmus paper blue.
and calculate the content ofC'7H,sNz06 in the tablet.
D. To 2 ml ofa 0.1 percent w/v solution add 2 ml of cyanogen
Other tests. Comply with the tests stated under Tablets. bromide solution and 3 ml of a 2.5 per cent w/v solution of
Assay. Weigh and powder 20 tablets. Weigh accurately a aniline and mix; a yellow colour is produced.
quantity of the powder containing 50 mg ofNifedipine into a
200 ml volumetric flask. Dissolve with the aid of 50 mt of Tests
methanol. Dilute to volume with methanol, mix and filter. Dilute Appearance of solution. The ;ubstance, in liquid form or
20 ml ofthe filtrate to 100 ml with methanol and mix. Measure liquefied by gentle heating, is clear (2.4.1), and not more
the absorbance of the resulting solution at the maximum at intensely coloured than reference solution YS5 (2.4.1).
about 350 nm (2.4.7). Calculate the content ofC17HlsNz06 £i'om
the absorbance obtained by repeating the operation with a pH (2.4.24). 6.0 to 7.8, detelmined in a 25.0 per cent w/v solution.
0.005 per cent w/v solution of nifedipine RS in methanol.
Congealing temperature (2.4.10).23° to 24.so.
Storage. Store protected from light and moisture.
Refractive index (2.4.27). 1.522 to 1.526.
Related substances. Detennine by thin-layer chromatography
(2.4.17), coating the plate with silica gel GF254.
Nikethamide Mobile phase. A mixture of 75 volumes of chloroform and
25 volumes of I-propanol.
Test solution. Dissolve 0.4 g of tile su'bstance under
examination in 10 ml of methanol.
Reference solution (a). A 0.04 per cent w/v solution of
ethylnicotinamide RS in methanol.
Reference solution (b). A 0.004 per cent w/v solution of
ethylnicotinamide RS in methanol. .
Mol. Wt. 178.2
Apply to the plate 10 J.lI. of each solution. After development,
Nikethamide isN,N-diethylpyridine-3-carboxamide. dry the plate in air and examine in ultraviolet light at 254 nm.
Nikethamide contains not less than 99.0 per cent and not more Any spot corresponding to ethylnicotinamide in the
than 101.0 per cent ofC IDH I4N zO, calculated on the anhydrous chromatogram obtained with the test solution is not more
basis. intense than the spot in the chromatogram obta~ned with
reference solution (a) and any other secondary spot is not
Category. CNS and Respiratory stimulant.
more intense than the spot in the chromatogram obtained
Dose. By slow intravenous injection, 500 mg to 2 g repeated at with reference solution (b).
intervals of 15 to 30 minutes as necessary.
Heavy metals (2.3.13).2.0 g complies with limit test for heavy
Description. A colourless or slightly yellowish, oily liquid or metals, Method B (10 ppm):
crystalline mass; odour, slight and characteristic.
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Identification Water (2.3.43). Not more than 0.3 per cent, detennined on
2.0g.
Test A may be omitted iftests B, C andD are carried out. Tests
C and D may be omitted iftests A and B are carried out. Assay. Weigh accurately about 0.15 g, dissolve in 20 ml of
anhydrous glacial acetic acid and 5 ml of acetic anhydride.
A. Determine by infrared absorption spectrophotometry (2.4.6).
Titrate with 0.1 M perchloric acid, determining the end-point
Compare the spectrum with that obtained with nikethamide
potentiometrically (2.4.25). Carry out a blank titration.
RS or with the reference spectrum ofnikethamide.
1 ml of 0.1 M perchloric acid is equivalent to 0.01782 g of
B. When examined in the range 230 nm to 360 nm (2.4.7), a
CIDHI~ZO.
0.002 per cent w/v solution shows an absorption maximum
only at about 263 nm; absorbance at about 263 nm, about 0.57. Storge. Storeprotected from light.

1783
NIKETHAMIDE INJECTION IP 2010

Nikethamide Injection resulting solution at the maximum at about 263 nm (2.4.7).


Calculate the content ofC IOH l4N zO taking 282 as the specific
Nikethamide Injection is a sterile solution containing 25 per absorbance at 263 nm.
cent w/v solution ofNikethamide in Water for Injections.
Storage. Store protected from light, in single dose containers.
Nikethamide Injection contains not less than 24.0 per cent
and not more than 26.0 per cent w/v solution of nikethamide,
CIOHI~zO.
Nitrazepam
Identification
A. Make I ml alkaline with 5 M sodium hydroxide, extract with
5 ml of dichloromethane and evaporate the solvent.
On the residue determine by infrared absorption
spectrophotometry (2.4.6). Compare the spectrum with that
obtained with nikethamide RS or with the reference spectrum
ofnikethamide.
B. Gives a voluminous precipitate with alkaline potassium
mercuri-iodide solution and a greyish-brown flocculent
precipitate with tannic acid solution. Gives no precipitate
Mol. Wt. 281.3
with iodine solution or with potassium mercuri-iodide
solution. Nitrazepam is 1,3-dibydro-7-nitro-5-phenyl-2H-1 ,4-
benzodiazepin-2-one.
C. Heat I ml with 0.2 g of sodium hydroxide; diethylamine,
recognisable by its odour, is evolved. Nitrazepam contains not less than 99.0 per cent and not more
than 101.0 per cent ClsHIIN303, calculated on the dried basis.
Tests
Category. Hypnotic; sedative.
pH (2.4.24).6.0 to 8.0.
Dose. 5 to 10 mg daily, at bed time.
Related substances. Determine by thin-layer chromatography Description. A yellow, crystalline powder; odourless or almost
(2.4.17), coating the plate with silica gel GF254.
odourless.
Mobile phase. A mixture of 75 volumes of chloroform and
25 volumes of I-propanol. Identification
Test solution. Dilute 1 ml ofthe injection to 5 ml with methanol. Test A may be omitted iftests B, C andD are carried out. Tests
B, C and D may be omitted if test A is carried out.
Reference solution (a). A 0.05 per cent w/v solution of
ethylnicotinamide RS in methanol. A. Determine by infrared absorption spectrophotometry (2.4.6).
Compare the spectrum with that obtained with nitrazepam RS
Reference solution (b). A 0.005 per cent w/v solution of
or with the reference spectrum of nitrazepam.
ethylnicotinamide RS in methanol.
B. Carry out the following procedure in subdued light.
Apply to the plate 10 III of each solution. After development,
dry the plate in air and examine in ultraviolet light at 254 nm. When examined in the range 230 nm to 360 nm (2.4.7), a freshly
Any spot corresponding to ethylnicotinamide in the prepared 0.0005 per cent w/v solution in a 0.5 per cent w/v
chromatogram obtained with the test solution is not more solution of sulphuric acid in methanol shows an absorption
intense than the spot in the chromatogram obtained with maximum only at about 280 nm; absorbance at about 280 nm,
reference solution (a) and any other secondary spot is not about 0.45.
more intense than the spot in the chromatogram obtained
C. Dissolve 10 mg in 1 ml of methanol, warming ifnecessary,
with reference solution (b).
and add 0.05 ml of 2 M sodium hydroxide; an intense yellow
Other tests. Complies with the tests stated under Parenteral colour is produced.
Preparations (Injections).
D. Dissolve 20 mg in a mixture of 5 ml of hydrochloric acid
Assay. Dilute 5.0 ml to 500.0 m1 with water. To 5.0 ml ofthe and 10 ml of water, boil for 5 minutes, cool and add 2 ml of a
solution add 5 ml of I M hydrochloric acid and sufficient 0.1 per cent w/v solution of sodium nitrite. Allow to stand for
water to produce 500.0 ml. Measure the absorbance of the 1 minute, add 1 ml ofa 0.5 percent w/v solution of sulphamic

1784
IP 2010 NITRAZEPAM TABLETS

acid, mix, allow to stand for 1minute, add 1ml ofa 0.1 per cent Mobile phase. A mixture of 100 volumes of chloroform and
w/v solution of N-(l-naphthyl)ethylenediamine 10 volumes of methanol.
dihydrochloride; a red colour is produced.
Test solution. Shake a quantity of the powdered tablets with
Tests sufficient methanol to produce a solution containing 5 mg of
Nitrazepam per ml, allow to settle and decant the supernatant
Related substances. Determine by thin-layer chromatography liquid.
(2.4.17), coating the plate with silica gel GF254.
Reference solution. A 0.5 per cent w/v solution of nitrazepam
Mobile phase. A mixture of 85 volumes of nitromethane and RS in methanol.
15 volumes of ethyl acetate.
Apply to the plate 2 III of each solution. After development,
Test solution. Dissolve 0.2 g of the substance under dry the plate in air, spray it with ethanolic sulphuric acid
examination in 10 ml of acetone. (10 per cent v/v), heat at 105° for 10 minutes and examine in
Reference solution. A 0.002 per cent w/v solution of the ultraviolet light at 365 nm. The principal spot in the
substance under examination in acetone. chromatogram obtained with the test solution corresponds to
that in the chromatogram obtained with the reference solution.
Apply to the plate 10 III of each solution. Allow the mobile
phase to rise 12 cm. Dry the plate in air and examine in ultraviolet C. To a quantity of the powdered tablets containing 5 mg of
light at 254 nm. Any secondary spot in the chromatogram Nitrazepam add 5 ml of hydrochloric acid and 10 ml of water,
obtained with the test solution is not more intense than the heat on a water-bath for 15 minutes, filter and cool. To the
spot in the chromatogram obtained with the reference solution. clear filtrate add 1 ml ofa 0.1 per cent w/v solution of sodium
nitrite, allow to stand for 3 minutes and add 1 ml of a 0.5 per
Heavy metals (2.3.13). 1.0 g complies with the limit test for
cent w/v solution of sulphamic acid. Allow to stand for
heavy metals, Method B (20 ppm).
3 minutes and add 1 ml ofa 0.1 per cent w/v solution ofN-(1-
Sulphated ash (2.3.18). Not more than 0.1 per cent. naphthyl) ethylenediamine dihydrochloride; a red colour is
Loss on drying (2.4.19). Not more than 0.5 per cent, determined produced.
on 1.0 g by drying in an oven at 105° for 4 hours.
Tests
Assay. Weigh accurately about 0.25 g, dissolve in 50 ml of
acetic anhydride. Titrate with 0.1 M perchloric acid, Dissolution (2.5.2).
determining the end-point potentiometrically (2.4.25). Carry Apparatus No.1,
out a blank titration. Medium. 900 ml of 0.1 M hydrochloric acid,
1 ml of 0.1 M perchloric acid is equivalent to 0.02813 g of Speed and time. 50 rpm and 45 minutes.
ClsHIlN303. Withdraw a suitable volume ofthe medium and filter. Measure
Storage. Store protectedfrom light and moisture. the absorbance of the filtrate, suitably diluted ifnecessary, at
the maximum at about 280 nm (2.4.7). Calculate the content of
ClsHIIN303, in the medium from the absorbance obtained from
a solution of known concentration of nitrazapam RS in. the
Nitrazepam Tablets same medium.

Nitrazepam Tablets contain not less than 90.0 per cent and not D. Not less than 70 per cent of the stated amount of
more than 110.0 per cent of the stated amount ofnitrazepam, ClsH11N303.
ClsHIIN303. Related substances. Determine by thin-layer chromatography
Usual strengths. 5 mg; 10 mg. (2.4.17), coating the plate with silica gel GF254.
Mobile phase. A mixture of 40 volumes of nitromethane,
Identification
40 volumes of toluene and 20 volumes of chloroform.
Carry out the following procedure in subdued light. Test solution. Shake a quantity of the powdered tablets
A. When examined in the range 230 nm to 360 nm (2.4.7), the containing 40 mg ofNitra'zepam with 25 ml of chloroform,
final solution obtained in the Assay shows an absorption filter, carefully evaporate the filtrate to dryness and dissolve
maximum only at about 280 nm. the residue in 2 ml of chloroform.
B. Determine by thin-layer chromatography (2.4.17), coating Reference solution. Dilute 1 volume of the test solution to
the plate with silica gel G 200 volumes with chloroform.

1785
NITRAZEPAM TABLETS IP 2010

Apply to the plate 5 Jll of each solution. Allow the mobile Nitrofurantoin contains not less than 98.0 per cent-and not
phase to rise 12 cm. Dry the plate in air and examine in ultraviolet morethan 102.0 per cent ofCgH6N40 s, calculated on the dried
light at 254 nm. Any secondary spot in the chromatogram basis.
obtained with the test solution is not more intense than the
Category. Antibacterial.
spot in the chromatogram obtained with the reference solution.
Dose. 50 to 100 mg four times daily.
Uniformity of content. Comply with the test stated under
Tablets. Description. Lemon yellow crystals or a crystalline powder;
odourless or almost odourless.
NOTE - CarlY out thefollowing procedure in subdued light.
Powder 1 tablet, add 5 ml of water, mix and allow to stand for Identification
15 minutes protected fi'om light. Add 70 ml of a 0.5 per cent Carry out the following test in subdued light.
v/v solution of hydrochloric acid in methanol, shake for
15 minutes protected from light, add sufficient of the A. When examined in the range 230 nm to 400 nm (2.4.7), the
hydrochloric acid solution to produce 100.0 ml and filter. final solution obtained in the Assay shows absorption maxima
Dilute 10.0 ml ofthe filtrate with sufficient ofthe hydrochloric at about 266 nm and 367 nm; the ratio ofthe absorbance at the
acid solution to produce a solution containing 0.0005 per maximum at about 367 nm to that at the maximum at about
cent w/v solution of Nitrazepam. Measure the absorbance of 266nmis 1.36 to 1.42.
the resulting solution immediately at the maximum at about B. To 1 ml ofa 0.1 per cent w/v solution in dimethylformamide
280 urn (2.4.7). Calculate the content ofC,sHIIN303 in the tablet add 0.1 ml of 0.5 M ethanolic potassium hydroxide; a brown
taking 910 as the specific absorbance at 280 nm. colour develops.
Other tests. Comply with the tests stated under Tablets.
Tests
Assay. CarlY out the following procedure in subdued light.
Related substances. Detennine by thin-layer chromatography
Weigh and powder 20 tablets. Weigh accurately a quantity of (2.4.17), coating the plate with silica gel HF254.
the powder containing about 5 mg ofNitrazepam, add 5 ml of
water, mix and allow to stand for 15 minutes protected from Mobile phase. A mixture of 90 volumes of nitromethane and
light. Add 70 ml of a 0.5 per cent v/v solution of hydrochloric 10 volumes of methanol.
acid in methanol, shake for 15 minutes protected from light, Test solution. Dissolve 0.25 g of the substance under
add sufficient of the hydrochloric acid solution to produce examination in minimum volume of dimethylformamide and
100.0 ml and filter. Dilute 10.0 ml ofthe filtrate to 100.0 rnl with dilute to 10 ml with acetone.
the same solvent arid measure the absorbance of the resulting
Reference solution. Dilute 1 volume of the test solution to
solution immediately at the maximum at about 280 nm (2.4.7).
100 volumes with acetone.
Calculate the content ofCIsHIIN303 taking 910 as the specific
absorbance at 280 nm. Apply to the plate 10 Jll of each solution. After development,
dry the plate in air, heat at 105° for 5 minutes and examine in
Storage. Store protected from light and moisture.
ultraviolet light at 254 nm. Spray with phenylhydrazine
hydrochloride solution and heat the plate at 105° for further
10 minutes. Any secondaty spot in the chromatogram obtained
with the test solution is not more intense than the spot in the
Nitrofurantoin chromatogram obtained with the reference solution by both
methods of visualisation.
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Loss on drying (2.4.19). 5.0 to 7.1 per cent (hydrous fonn) and
not more than 1.0 per cent (anhydrous fonn), determined on
1.0 g by drying in an oven at 105°.
Assay. CarlY out the following procedure in subdued light.
CgH6N40 S Mol. Wt. 238.2 (anhydrous)
Weigh accurately about 75 mg and dissolve in 25.0 ml of
CgH6N40S,HzO Mol. Wt. 256.2 (hydrous)
dimethylformamide, add sufficient water to produce 500.0 ml
Nitrofurantoin is 1-(5-nitrofurfurylideneamino)imidazolidine- and mix. Dilute 5.0 ml to 100.0 ml with a solution containing
2,4-dione. It is anhydrous or contains one molecule of water 1.8 per cent w/v solution of sodium acetate and 0.14 per cent
of hydration. v/v of glacial acetic acid. Measure the absorbance of the

1786
IP 2010 NITROFURAZONE

resulting solution at the maximum at about 367 nm (2.4.7), acid. Measure the absorbance of the resulting solution at the
using as the blank the sodium acetate-acetic acid solution. maximum at about 367 urn (2.4.7), using as the blank the sodium
Calculate the content ofCsH 6N40 s taking 765 as the specific acetate-acetic acid solution. Calculate the content ofCsH6N 40 s
absorbance at 367 nm. taking 765 as the specific absorbance at 367 run.
Storage. Store protected from light and moisture. Storage. Store protected from light and moisture.
Labelling. The label states whether the material is anhydrous
or hydrous. .

Nitrofurazone
Nitrofurantoin Tablets
Nitofural
Nitrofurantoin Tablets contain not less than 90.0 per cent and
not more than I 10.0 per cent of the stated amount of
nitrofurantoin, CSH 6N4 0 S '
Usual strengths. 50 mg; 100 mg.

Identification
C6H6N40 4 Mol. Wt. 198.1
CarlY out the following proceduJ'e in subdued light.
Nitrofurazone is 5-nitro-2-furaldehyde semicarbazone.
A. When examined in the range 230 nm to 400 nm (2.4.7), the
final ~olution obtained in the Assay shows absorption maxima Nitrofurazone contains not less than 97.0 per cent and not
at about 266 nm and 367 nm. more than 103.0 per c.ent ofC 6H 6N 40 4 , calculated on the dried
basis.
Tests Category. Antibacterial.
Related substances. Detelmine by thin-layer chromatography
Description. A yellow to brownish-yellow, crystalline powder;
(2.4.17), coating the plate with silica gel HF254.
odourless or almost odourless.
Mobile phase. A mixture of 90 volumes of nitromethane and
10 volumes of methanol. Identification
Test solution. Shake a quantity of the powdered tablets A. Detennineby infrared absorption spectrophotometry (2.4.6).
containing 0.1 g ofNitrofurantoin with 10 ml of a mixture of Compare the spectrum with that obtained with nitrojitrazone
9 volumes of acetone and 1 volume of dimethylformamide RS or with the reference spectrum ofnitrofurazone.
and filter.
B. Dissolve 1 mg in 1 ml of dimetliylfohnamide and add 0.05 ml
Reference solution. Dilute 1 volume of the test solution to 'of 1 M ethanoUc potassium hydroxide; a ruby red colour is
100 volumes with acetone. produced.
Apply to the plate 10 III of each solution. After development,
dry the plate in air, heat at 105° for 5 minutes and examine in Tests
ultraviolet light at 254 nm. Spray with phenylhydrazine
pH (2.4.24).5.0 to 7.0, detennined in the filtrate obtained by
hydrochloride solution and heat the plate at 105° for further
shaking 1.0 g with 100 ml of carbon dioxide-free water and
10 minutes. Any secondary spot in the chromatogram obtained
filtering.
with the test solution, is not more intense than the spot in the
chromatogram obtained with the reference solution by both Related substances. Detennine by liquid chromatography
methods of visualisation. (2.4.14).
Other tests. Comply with the tests stated under Tablets. Test solution. Dissolve 100 mg of the substance under
examination in 100.0 ml ofthe mobile phase.
Assay. Carry out the following procedure in sub.dued light.
Reference solution (a). A 0.0005 per cent w/v solution of(5-
Weigh and powder 20 tablets. Weigh accurately a quantity of
nitro-2-fil1yl)methylene diacetate (Nitrofurazone impurity
the powder containing about 0.15 g of Nitrofurantoin, add
B) in the mobile phase.
50.0 ml of dimethylformamide, shake for 5 minutes, add
sufficient water to produce 1000.0 ml and mix. Dilute 5.0 rnI to Reference solution (b). Dissolve 10 mg each ofnitrojitral RS
100.0 ml with a solution containing 1.8 per cent w/v solution and nitrojitrantoin in 100 ml of the mobile phase. Dilute 5 ml
of sodium acetate and 0.14 per cent v/v of glacial acetic of this solution to 100 ml with the mobile phase.

1787
NITROFURAZONE IP 2010

Chromatographic system Category. General anaesthetic.


a stainless steel column 25 em x 4.6 mm, packed with Dose. By inhalation, 60 to 80 per cent, with oxygen 20 to 40 per
octadecylsilane bonded to porous silica (5 /!m), cent, as required.
- mobile phase: a mixture of 40 volumes of acetonitrile
and 60 volumes of water, Description. A colourless gas; odourless.
- flow rate. 1 ml per minute,
- spectrophotometer set at 310 nm, Identification
- injection volume. 20 Ill. A. A glowing splinter of wood bursts into flame on contact
Inject reference solution (b). The test is not valid unless the with the gas.
resolution between the peaks due to nitrofural and B. Shake with alkaline pyrogallol solution; the gas being
nitrofurantoin is not less than 2.0. examined is not absorbed and the solution does not become
Inject the test solution and reference solution (a). Run the brown.
chromatogram 10 times the retention time ofnitrofural. In the
chromatogram obtained with the test solution, the area of any Tests
secondary peak is not more than the area ofthe principal peak
Acidity or alkalinity. Use hermetically-closed, flat-bottomed,
in the chromatogram obtained with reference solution (a) (0.5
glass cylinders with dimensions such that 50 ml of liquid
per cent) and the sum of the areas of all the secondary peaks
reaches a height of 12 to 14 em, fitted with an outlet tube and
is not more than twice the area of the principal peak in the
with an inlet tube with an orifice of 1 mm in internal diameter
chromatogram obtained with reference solution (a) (1.0 per
reaching to within 2 mm of the bottom of the cylinder. For
cent). Ignore any peaks with the area less than 0.05 times the
solution (1) pass 2.0 litres ofthe gas under examination through
area ofthe principal peak in the chromatogram obtained with
a mixture of 0.1 ml of O. 01 M hydrochloric acid and 50 ml of
reference solution (a) (0.025 per cent).
carbon dioxide-free water. For solution (2) use 50 ml of carbon
Sulphated ash (2.3.18). Not more than 0.1 per cent. dioxide-free water. For solution (3) add 0.2 ml of 0.01 M
Loss on drying (2.4.19). Not more than 0.5 per cent, determined hydrochloric acid to 50 ml of carbon dioxide-free water. To
on 1.0 g by drying in an oven at 105 0 • each solution add 0.1 ml of a 0.02 per cent w/v solution of
methyl red in ethanol (70 per cent). The intensity ofthe colour
Assay. Carry out the following procedure in subdued light.
of solution (1) is between those of solutions (2) and (3).
Weigh accurately about 60 mg, add 20.0 ml of
dimethylformamide, swirl to dissolve and add sufficient water Arsine and phosphine. Through a mercuric chloride paper
to produce 500.0 m!. Dilute 5,0 ml ofthe solution to 100.0 ml attached to a glass tube as in the limit test for arsenic (2.3.10),
with water and mix. Measure the absorbance of the resulting pass 2.0 litres of the gas; no visible stain is produced.
solution at the maximum at about 375 nm (2.4.7). Calculate the Carbon dioxide. Not more than 300 ppm v/v determined by the
content ofC 6H 6N 40 4 taking 822 as the specific absorbance at following method. Use the apparatus described in the test for
375nm. Acidity or alkalinity. Pass 1.0 litre through 50 ml ofclear barium
Storage. Store protected from light and moisture. hydroxide solution. Any turbidity produced in the resulting
solution is not more. than that obtained in a reference solution
prepared at the same time by adding 1 ml of a 0.11 per cent
Nitrous Oxide w/v solution of sodium bicarbonate in carbon dioxide-free
water to 50 ml of barium hydroxide solution.
Mol. Wt. 44.0
Carbon monoxide. Notmore than 10 ppm v/v, determined by
Nitrous Oxide contains not less than 98.0 per cent v/v ofNzO. the following method. Connect in series a U-tube containing
NOTE - Carry out thefollowing tests on afull cylinderfrom silica gel impregnated with chromium trioxide, a drechsel
which no gas has been withdrawn. The cylinder from which bottle containing 100 ml of a 40 per cent w/v solution of
the gas is taken should be kept at room temperature for not potassium hydroxide, a U-tube containing pellets of
less than 6 hours before carrying out the tests. Keep the potassium hydroxide, a U-tube containing phosphorus
cylinder in the vertical position with the outlet valve pentoxide dispersed on previously granulated, fused pumice,
uppermost and deliver the gas at a rate of 4 litres per hour, a tube containing iodine pentoxide in granules, previously
unless otherwise directed. The test for Carbon monoxide dried at 200 0 and kept at a temperature of 1200 , packed in I-em
should be carried out on the first portion ofgas drawn from columns separated by I-em columns of glass wool giving an
the cylinder and that for Nitric oxide and nitrogen dioxide effective length of 5 em, and a flask containing 2.0 ml of 1 M
immediately thereafter. potassium iodide and 0.15 ml of starch solution.

1788
IP 2010 NORADRENALINE BITARTRATE

Flush the apparatus with 5.01itres of carbon dioxide-free air Water. Pass a measured quantity at a rate of6litres per hour
and, if necessary, discharge the blue colour in the iodide through an absorption tube containing magnesium
solution by adding a small quantity of freshly prepared perchlorate; the increase in weight ofthe tube does not exceed
0.002 M sodium thiosulphate. Continue flushing until not 2 mg per litre ofgas, the initial and final weighings ofthe tube
more than 0.045 ml of0.002 M sodium thiosulphate is required being made when the air in it has been displaced by the nitrous
after passing 5.0 litres ofcarbon dioxide-free air. Pass 5.0 litres oxide.
ofthe gas under examination through the apparatus and flush Assay. Carry out the assay of nitrous oxide (2.3.32), using
the last traces of liberated iodine into the reaction flask by 100 ml ofthe gas under examination. Use a cylinder ofthe gas
passing through the apparatus 1.0 litre of carbon monoxide- under examination from which at least 1 per cent w/w of the
free air. Titrate the liberated iodine with 0.002 M sodium contents have been removed.
thiosulphate. Carry out a blank titration under the same
Storage. Store under pressure in metal cylinders of the type
conditions, using 5.0 litres of carbon dioxide-free air. The
conforming to the appropriate safety regulations and at a
difference between the volumes of 0.002 M sodium
temperature not exceeding 37°.
thiosulphate used in the two titrations is not greater than
1.0rnl. Labelling. The cylinder is painted blue and carries a label
stating "Nitrous Oxide". In addition, ''Nitrous Oxide" or the
Halogens and hydrogen sulphide. Pass a volume containing symbol ''N20'' should be stencilled in paint on the shoulder of
1.0 litre measured at 25° and at 101.3 kPa through a mixture of the cylinder. .
100 ml of water and 1 ml of silver nitrate solution; neither
opalescence nor darkening is produced.
Nitric oxide and nitrogen dioxide. Not more than 2 ppm v/v in Noradrenaline Bitartrate
both the liquid and gaseous phases, determined by the
following method. Use two of the cylinders described in the Noradrenaline Acid Tartrate; Levarterenol Bitartrate;
test for Acidity or alkalinity connected in series. Examine Norepinephrine Bitartrate
separately both the liquid and gaseous phases of the gas
OH
under examination. To obtain the liquid phase invert the
cylinder. The liquid vaporises on leaving the valve.
For solution A dissolve 1 g ofsulphanilic acid in a mixture of
10 ml ofglacial acetic acid and 180 ml ofwater. For solution
0
HO~ .
NH2 H OH
HOOe)( eOOH ,H 20
. HXOH
B dissolve 0.2 g of N-(l-naphthyl)ethylenediamine OH
dihydrochloride in 10 ml of a 50 per cent v/v solution of CSHIIN03,C4Ht;06,H20 Mol. Wt. 337.3
glacial acetic acid, heating gently, and dilute to 200 ml with
water. Mix 9 volumes ofsolution A with 1 volume ofsolution Noradrenaline Bitartrate is (R)-2-amino-l-(3,4-
B (reagent A). dihydroxyphenyl)ethanol tartrate monohydrate.
Noradrenaline Bitartrate contains not less than 98.5 per cent
In the first cylinder place 15 ml ofa solution containing 2.5 per
and not more than 101.0 per cent of CSHllN03,C4H606,
cent w/v solution of potassium permanganate and 1.2 per
calculated on the anhydrous basis.
cent v/v ofsulphuric acid (96 per cent). Place 20 ml ofreagent
A in the second cylinder and connect the outlet tube of the Category. Sympathomimetic.
first cylinder to the inlet tube of the second cylinder. Pass
Dose. By intravenous infusion, 2 to 20 /Lg per minute, according
2.5 litres ofthe gas under examination through the reagents at
to the blood pressure of the patient.
a rate of 15 litres per hour. Prepare a reference solution by
adding 0.25 ml of a 0.00616 per cent w/v solution ofsodium Description. A white or almost white, crystalline powder;
nitrite to 20 ml of reagent A. Allow both the sample and odourless. It gradually darkens on exposure to air and light.
reference solutions to stand for 10 minutes. For both liquid
and gaseous phases, any red colour in the sample solution is Identification
not more intense than that in the reference solution. Test A may be omitted iftests B, C, D, E andF are carried out.
Oxidising substances. Pass a volume containing 2.0 litres Tests C, D, E may be omitted iftests A, BandF are carried out.
measured at 25° and at 101.3 kPa through a freshly prepared A. Dissolve 0.2 g in 2 ml ofwater containing about 10 mg of
solution of 0.5 g of soluble starch and 0.5 g of potassium sodium sulphite and add sufficient dilute ammonia solution
iodide in 100 ml ofwater containing 0.05 ml ofglacial acetic to give an alkaline reaction. Keep the mixture at about 4° for
acid; the colour of the liquid is not changed. 1 hour and filter.

1789
NORADRENALINE BITARTRATE IP 2010

On the residue (residue R) determine by infrared absorption bands 20mm by 2 mm. Allowthe applied bands to dry in air,
spectrophotometry (2,4,6). Compare the spectrum with that spray them with a saturated solution of sodium bicarbonate,
obtained with noradrenaline acid tartrate RS treated in the allow to dry in air and spray the' bands twice with acetic
same manner. anhydride, drying between the two sprayings. Heat the plate
B. When examined in the range 230 nm to 360 nm (2.4.7), a at. 50° for 90 minutes and develop the chromatograms. After
0.005 per cent w/v solution in 0.01 M hydrochloric acid shows removal of the plate, allow it to dry in air and spray with a
an absorption maximum at about 279 nm; absorbance at about freshly prepared mixture of8 volumes of methanol, 2 volumes
279 nin, about 0.40. of ethylenediamine and 2 volumes of a 0.5 per cent w/v
solution of potassium ferricyanide. Dry the plate at 60° for
C. Wash residue R obtained in test A with three quantities,
10 minutes and examine in ultraviolet light at 254 and 365 nm.
each of2 ml, of water, followed by 5 ml of ethanol (95 per
, In the chromatogram obtained with the test solution any band
cent) and 5 ml of ether and dry the precipitate under preSSUTe
with a slightly higher R r value than the principal band is not
of 1.5 to 2.5 kPa for 3 hours. The specific optical rotation
more intense than the corresponding band in the chromatogram
(2.4.22), determined in a 2.0 per cent w/v solution,ofthe dried
obtained with reference solution (b). The chromatogram
precipitate in 0.5 M hydrochloric acid is -44° ,to -48°.
obtained with reference solution (c) shows a clearly separated
D. To 1 ml of a 1 per cent w/v solution,add 0,05 ml offerric band corresponding to the most intense band in the
chloride solution; an intense green colour is produced. Add, chromatogram obtained with reference solution (a) at a higher
drop by drop, sodiwn bicarbonate solution; ,the colour R r value than the most intense band.
changes to blue and then red.
Noradrenalone. Absorbance of a 0.2 per cent w/v solution in
E. To 1 ml ofa 0.1 per cent w/v solution add 10 ml ofphthalate
0.01 M hydrochloric acid at 310 nm, not more than 0.40 (2.4.7).
btifferpH 3.6, add 1 ml of O. 05 M iodine, setaside for 5 minutes , . . ' :

and add 2 ml of 0.1 M sodium thiosulphate; not more than a Sulph~ted ash (2.3.18). Not more than 0.1 percent.
faint red colour is produced; Repeat the test using buffei· Water (2.3.43). 4.5 to 5.8 per cent, determined on 0.5 g.
solution pH 6.6 instead of phthalate buffer pH 3.6; a strong
reddish violet colour is produced (distinction from adrenaline Assay. Weigh accurately about 0.6 g, dissolve in 50 ml of
and isoprenaline). anhydrous glacial acetic acid, warming if necessary.Titrate
with 0.1 M perchloric acid, using Clystal violet solutiOn as
F. The filtrate obtained in test A gives the reactions oftartrates indicator, until a bluish green colour is obtained. Carry out a
(2.3.1).
blank titration.
Tests 1 ml of 0.1 M perchloric acid is equivalent to 0.03193 g of
Appearance of solution. A freshly prepared 2.0 per cent w/v CgHIIN03,CJf606.
solution is clear (2.4.1), and not more intensely coloured than Storage. Store protected from moisture.
reference solution BYS5 (2.4.1).
pH (2.4.24). 3.5 to 5.0, detennined in a 1.0 per centw/v solution.
Melting range (2.4.21). 100° to 106°, with decomposition. Noradrenaline Bitartrate Injection
Adrenaline. Determine by thin-layer chromatography (2.4.17),
Noradrenaline Acid Tartrate Injection; Noradrenaline
coating the plate with silica gel G
Injection; Levarterenol Bitartrate Injection;
Mobile phase. A mixture of50 volumes of acetone, 50 volumes Norepinephrine Bitartrate Injection
of dichloromethane and 0.5 volume ofanhydrousformic acid.
Noradrenaline Bitartrate Injection is a sterile solution of
Prepare the following solutions immediately before use. Noradrenaline Bitartrate. It is prepared by diluting Sterile
Test solution. Dissolve 0.25g of the substance under Noradrenaline Concentrate to 250 times its volume with Sodium
examination in 10 ml of water. Chloride and Dextrose Injection or with Dextr'ose Injection
Reference solution (a). A 0.125 per cent w/v solution of (5 per cent w/v) immediately before use.
adrenaline tartrate RS in water. Noradrenaline Bitmtrate Injection contains in 1 ml 8 Ilg of
Reference solution (b). A 0.025 per cent w/v solution of Noradrenaline Bitmtrate equivalent to approximately 4 Ilg of
adrenaline tartrate RS in water. noradrenaline.
Reference solution (c). A mixture of equal volumes ofthe test
solution and reference solution (b).
Tests
Apply to the plate 6 III of each of test solution, reference Other tests. Complies with the tests stated under Parenteral
solutions (a) and (b) and 12 III of reference solution (c) as Preparations (Injections).

1790
IP 2010 NORETHISTERONE

Sterile Noradrenaline Concentrate Norethisterone contains not less than 98.0 per cent and not
more than 102.0 per cent of CZOHZ60Z, calculated on the dried
Sterile Noradrenaline Concentrate is asterile, isotonic solution
basis.
containing 0.2 per cent w/v of Noradrenaline Bitartrate in
Water for Injections. Category. Progestogen.
.. ,.

Sterile Noradrenaline C,onceiltr.ate contains not less than Dose. 5 to 20 mg daily, in single or divided doses.
0.18 per cent and not more than 0.23 per cent w/v of
Description. A white or yellowish-white, crystalline powder;
noradrenaline bitartrate, CgHIIN03,C4H606,HzO.
odourless.
Identification
Identification
Mix 0.5 ml with 10 ml ofphthalate bufferpH 3.6, add l'ml of
A. Detennine by inli"ared absorption spectrophotometry (2.4.6).
0.05 M iodine, allow to stand for 5 minutes and add 2 ml of
Compare the spectrum with that obtained with norethisterone
0.1 M sodium thiosulphate; not more than a velY faint red
RS or with the reference spectrum of norethisterone.
colour is produced. Repeat the test using phosphate buffer
pH 6.6 instead of phthalate buffer pH 3.6; a strong reddish B. Determine by thin~layer chromatography (2.4.17), coating
violet colour is produced; the plate with silica gel G: '

Tests Solvent n1ixture. A mixture of 90 volumes of acetone and


10 volliines offormamide.
pH (2.4.24). 3.0 to 4.6.
Mobile phase. A mixture of 40 volumes of hexane and
Other tests. Complies with the tests stated under Parenteral 10 volumes of dioxan.
Preparations (Concentrated Solutions for Injection).
Test solution. Dissolve 10 mg of the substance under
Assay. Dilute 5.0 ml to 200.0 ml with water and measure the examination in 10 ml of chloroform.
absorbance ofthe resulting solution at the maximum at about
Reference solution. Dissolve 10 mg of norethisterone RS in
279 nm (2.4.7). Calculate the content ofCgH"N03,C4H606,HzO
taking 80 as the specific absorbance at 279 nm.. 10 nil of chloroform.

Storage. Store protected from light, in single dose containers. Place the dry plate in a tank containing a shallow layer of the
solvent mixture, allow the solvent mixture to ascend to the
Labelling. The label states (1) "Sterile Noradrenaline top, remove the plate from the tank and allow the solvent to
Concentrate"; (2) that 1 voillme of the solution diluted to evaporate. Use within 2 hours, with the flow of the mobile
250 volumes with Sodium Chloride and Dextrose Injectionor phase in the direction in which the aforementioned treatment
with Dextrose Injection (5 per cent w/v) produces was done.
Noradrenaline Bitartrate Injection, which must be used
immediately after preparation; (3) that ifthe solution isbrbwn Apply to the plate 2 J..lI of each solution. Allow the mobile
it should not be used. phase to l~ise 12 cm. DIy the plate in a current ofwann air, allow
the solvent to evaporate, heat at 1200 for 15 minutes and spray
the hot plate with ethanolic sulphuric acid (20 per cent v/v).
Heat at l20~ for a further 10 minutes, allow to cool and examine
in daylight and in ultraviolet light at 365 nm. The principal
Norethisterone spot in the chromatogram obtained with the test solution
Norethindrone corresponds to and exhibits fluorescence similar to that in tIie
chromatogram obtained with the reference solution.
OH C. Dissolve about 2 mg in 2 ml of ethanol (95 per cent) and
-C=CH add 1 ml of a 1 per cent w/v solution of butylated
hydroxytoluene in ethanol (95 per cent) and 2 ml of I M
sodium hydroxir;fe. Heat in a water~bath for 30 minutes and
cool; a yellowi,sh pink colour is produced. '
o Tests
Mol. Wt. 298.4 Appearance of solution. Dissolve 0.2 g in sufficient dioxan to
Norethisterone is 17~-hydroxy-19-nor-17 a-pregn-4-en-20-yn- produce 10 ml (solution A). The solution is clear (2.4.1), and
3-one. not more intensely coloured than reference solution YS6 (2.4.1).

1791
NORETHISTERONE IP 2010

Specific optical rotation (2.4.22). -33.0° to -37.0°, determined Assay. Weigh accurately about 0.4 g," dissolve in 40 ml of
in a solution prepared by diluting 5.0 ml of solution A to tetrahydrofuran, add 10 ml of a 10 per cent w/v solution of
10.0 ml with dioxan. silver nitrate and titrate with 0.1 M sodium hydroxide using
Light absorption. Dissolve 10 mg in sufficient ethanol 2 ml of bromocresol green solution as indicator. Repeat the
(95 per cent) to produce 100 ml, dilute 10 ml ofthe solution to operation without the substance under examination. The
100 ml with methanol (98 per cent). Absorbance of the difference between the titrations represents the amount of
resulting solution at the maximum at about 240 nm, 0.55 to 0.59 sodium hydroxide required.
(2.4.7). 1 ml of 0.1 M sodium hydroxide is equivalent to 0.02984 g of
Related substances. Determine by liquid chromatography CZOHZ60Z'

(2.4.14). Storage. Store protected from light and moisture.


Solvent mixture. A mixture of 40 volumes of water and 60
volumes of acetonitrile.
Test solution. Dissolve 25 mg of the substance under
examination in 10 ml ofthe solvent mixture. Norethisterone Tablets
Reference solution. Dilute 1.0 ml ofthe test solution to 100.0
Norethindrone Tablets
ml with the solvent mixture. Dilute 1.0 ml ofthis solution to
10.0 ml with the solvent mixture. Norethisterone Tablets contain not less than 90.0 per cent
and not more than 110.0 per cent of the stated amount of
Chromatographic system
norethisterone, CZOHZ60Z'
- a stainless steel column 15 cm x 4.6 mm, packed with
end-capped octylsilane bonded to porous silica (5 J!m), Usual strength. 5 mg.
mobile phase: A. water,
B. acetonitrile, Identification
a linear gradient programme using the condition given
below, Place a quantity of the powdered tablets containing 25 mg of
flow rate. 1 ml per minute, Norethisterone on a small filter, wash with three quantities,
spectrophotometer set at 254 nrn, each of 5 ml, of light petroleum (60° to 80°) and discard the
injection volume. 20 J!l. washings. Extract the residue with 15 ml of chloroform,
evaporate the extract to dryness and recrystallise from aqueous
Time Mobile phase A Mobile phase B
methanol. The residue complies withthe following test.
(in min.) (per cent w/v) (per cent w/v)
0-20 63 37 Determine by thin-layer chromatography (2.4.17), coating the
plate with silica gel G.
20-25 63-20 37-80
Solvent mixture. A mixture of 90 volumes of acetone and
25-35 20 80
10 volumes of 1,2-propanediol.
35-36 20-63 80-37
Mobile phase. A mixture of40 volumes of cyclohexane and 10
36-50 63 37
volumes of toluene.
Inject the test solution and the reference solution. In the
Test solution. Dissolve 25 mg of the substance under
chromatogram obtained with the test solution, the area of any
examination in 10 ml ofthe solvent mixture.
secondary peak is not more than twice the area ofthe principal
peak in the chromatogram obtained with the reference solution Reference solution (a). Dissolve 25 mg of norethisterone RS
(0.2 per cent) and the sum of the areas of all the secondary in 10 ml ofthe solvent mixture.
peaks is not more than 3 times the area ofthe principal peak in
Reference solution (b). Mix equal volumes ofthe test solution
the chromatogram obtained with reference solution (0.3 per
and reference solution (a).
cent). Ignore any peaks with the area less than 0.5 times the
area of the principal peak in the chromatogram obtained with Place the dry plate in a tank containing a shallow layer of the
the reference solution (0.05 per cent). solvent mixture, allow the solvent mixture to ascend to the
top, remove the plate from the tank and allow the solvent to
Sulphated ash (2.3 .18). Not more than 0.1 per cent.
evaporate. Use within 2 hours, with the flow of the mobile
Loss on drying (2.4.19). Not more than 0.5 per cent, determined phase in the direction in which the aforementioned treatment
on 1.0 g by drying in an oven at 105° for 3 hours. was done.

1792
IP 2010 NORFLOXACIN

Apply to the plate 2 J.ll of each solution. Allow the mobile N orfloxacin
phase to rise 12 cm. Dry the plate in a current ofwarm air, allow
the solvent to evaporate, heat at 120 0 for 15 minutes and spray
the hot plate with ethanolic sulphuric acid (20 per cent v/v).
Heat at 1200 for a further 10 minutes, allow to cool and examine
in daylight and in ultraviolet light at 365 nm. The principal
spot in the chromatogram obtained with the test solution
corresponds to that in the chromatogram obtained with
reference solution (a). The principal spot in the chromatogram
obtained with reference solution (b) appears as a single,
compact spot.
Mol. WUI9.3
Tests
Norfloxacin is l-ethyl-6-fluoro-4-oxo-7-(piperazin-l-yl)-l ,4-
Uniformity ofcontent. (For tablets containing 10 mg or less)- dihydroquinoline-3-carboxylic acid.
Comply with the test stated under Tablets. Norfloxacin contains not less than 99.0 per cent and not more
Carry out the procedure described under Assay but using the than 101.0 per cent ofC16H18FN303, calculated on the dried
following test solution. basis.
Category. Antibacterial.
Test solution. Powder one tablet and dissolve as completely
as possible in 2 ml of water with the aid of ultrasound for 15 Dose. 400 mg to 800 g daily, in divided doses.
minutes and dilute to 5.0 ml with methanol. Centrifuge for 15 Description. A white to pale yellow, crystalline powder.
minutes and use the clear supernatant liquid.
Calculate the content of C2oH2602 in the tablet. Identification
Other tests. Comply with the tests stated under Tablets. A. Determine by infrared absorption spectrophotometry (2.4.6).
Compare the spectrum with that obtained with norfloxacin
Assay. Determine by liquid chromatography (2.4.14). RS or with the reference spectrum ofnorfloxacin.
Test solution. Weigh and powder 20 tablets. Disperse a B. When examined in the range 230 nm to 360 urn (2.4.7), a
quantity ofpowder containing about 5 mg of Norethisterone 0.0005 per cent w/v solution in 0.1 M sodium hydroxide shows
in 10 ml of water, sonicate for 15 minutes and dilute to 25.0 ml an absorption maximum at about 273 urn.
with methanol, filter.
Tests
Reference solution. A 0.02 per cent w/v solution of
norethisterone RS in methanol. Related substances. Determine by thin-layer chromatography
Chromatographic system (2.4.17), coating the plate with silica gel G, previously washed
- a stainless steel column 25 cm x 4.6 mm, packed with with methanol and dried.
octadecylsilane bonded to porous silica (10 J.lm) (Such Mobile phase. A mixture of 40 volumes of dichloromethane,
as Spherisorb ODS 1), 40 volumes of methanol, 20 volumes of toluene, 14 volumes
mobile phase: a mixture of28 volumes of water and 72 of diethylamine and 8 volumes of water.
. volumes of methanol, Test solution. Dissolve 0.8 g of the substance under
- flow rate. 1 ml per minute, examination in 100 rnl ofa mixture ofequal volumes ofmethanol
- spectrophotometer set at 254 urn, and dichloromethane.
- injection volume. 20 J.ll.
Reference solution. Dissolve 4.0 mg ofnorfloxacin RS in 1 ml
Inject the reference solution. The test is not valid unless the of glacial acetic acid, add 4 ml of methanol and mix; dilute
relative standard deviation for replicate injections is not more 1 mlofthe solution with 9 ml ofamixture ofequal volumes of
than 2.0 per cent. methanol and dichloromethane (reference solution A). Dilute
Inject the reference solution and the test solution. a portion ofreference solution A with an equal volume ofthe
methanol-dichloromethane mixture (reference solution B).
Calculate the content of C2oH2602 in the tablets.
Apply separately to the plate spots of the three solutions in
Storage. Store protected from light and moisture. quantities indicated below. For spot 1 use 5 J.lI of the test

1793
NORFLOXACIN IPZ010

solution; for spots 2, 3 and 4 use 1 J.ll, 1.5 J.ll and2 J.ll respectively Other tests. Comply with the tests stated under Eye Drops.
ofreference solution A; for spot 5 use 5 J.ll ofreference solution
Assay. Detennine by liquid chromatography (2.4.14).
B. Place the plate in a paper-lined chamber previously
equilibrated with the mobile phase and allow the solvent front Test solution. Dilute a suitable volume ofthe eye drops with a
to move about nine-tenths of the length of the plate. After 0.1 per cent v/v solution of orthophosphoric acid to produce
development, dry the plate in air and examine in ultraviolet a solution containing 0.Q05 per cent w/v ofNorfloxacin.
light at 254 nm and 365 run. Compare the intensities of any Reference solution. A 0.005 per cent w/v solution of
secondary spots in the chromatogram obtained with the test nOifloxacin RS inO.1per cent v/v solution of orthophosphoric
solution with those ofthe principal spots (2), (3), (4) and (5). acid.
The sum of the intensities of secondary spots obtained with
the test solution is not more than 0.5 per cent of impurities. Chromatographic system
(The spots (2) (3) (4) and (5) represent 0.2 per cent, 0.3 per a stainless steel column 30 cm x 3.9 mm, packed with
cent, 0.4 per cent and 0.5 per cent respectively of impurities). octadecylsilane bonded to porous silica (10 J.lm) (Such
as Bondapack C 18),
Heavy metals (2.3.13).1.33 g complies with the limit test for column temerature. 50°,
heavy metals, Method B (15 ppm). mobile phase: a mixture of 300 volumes of methanol
Sulphated ash (2.3.18). Not more than 0.1 per cent, detennined and 700 volumes of 0.1 per cent v/v orthophosphoric
on 1.0 g in a platinum crucible. acid, .
flow rate. 2 ml per minute,
Loss on drying (2.4.19). Not more than 1.0 per cent, detennined
spectrophotometer set at 280 nm,
on 0.5 g by drying in an oven at 100° at a pressure not exceeding
- injection volume. 20 J.ll.
0.7kPa.
Precondition the column using 0.01 M anhydrous sodium
Assay. Weigh accurately about 0.3 g and dissolve in 100 ml of
dihydrogen orthophosphate, adjusted to pH 4.0 with
anhydrous glacial acetic acid. Titrate with 0.1 M perchloric orthophosphoric acid, at a flow rate of0.5 ml per minute for 8
acid, detennining the end-point potentiometrically (2.4.25) and hours. Equilibrate the column with the mobile phase for about
using a suitable anhydrous electrode system. (The electrode
30 minutes before starting the chromatography.
system may be rendered anhydrous by filling the electrode
Inject the reference solution. The test is not valid unless the
with 0.1 M lithium perchlorate in acetic anhydride after
tailing factor is not more than 2.0. The relative standard
removing any aqueous solution contained in it). Carry out a
deviation for replicate injections is not more than 2.0 per cent.
blank titration.
Inject altemately the test solution and the reference solution.
1 ml of 0.1 Mperchloric acid is equivalent to 0.03193 g of
C16HISFN303' Calculate the content of C16H.ISFN303 in the eye drops.
Storage. Store protected from light and moisture. Storage. Store protected from light.

Norfloxacin Eye Drops Norfloxacin Tablets


Norfloxacin Eye Drops are a sterile solution ofNorfloxacin in Norfloxacin Tablets contain not less than 90.0 per cent and
PUlified water. not more than 110.0 per cent of the stated amount of
Norfloxacin Eye Drops contain not less than 90.0 percent and norfloxacin, C16HISFN303'
not more than 110;0 per cent of the stated amount of Usual strengths. 200 mg; 400 mg; 800 mg.
norfloxacin, C16HlsFN303'
Identification
Usual strength. 0.3 per cent w/v.
A. Determine by thin-layer chromatography (2.4.17), coating
Identification the plate with silica gel GF254.

In the Assay, the principal peak in the chromatogram obtained Mobile phase. A mixture of 40 volumes of chloroform,
with the test solution corresponds to the peak in the 40 volumes of methanol, 20 volumes of toluene, 14 volumes
chromatogram obtained with the reference solution. of diethylamine and 8 volumes of water.
Test solution. Shake a quantity ofthe fine~y powdered tablets
Tests
containing 75 mg ofNorfloxacin with 50 ml of a mixture of
pH (2.4.24).4.6 to 5.5. equal volumes of acidified methanol (containing 0.9 per cent

1794
IP 2010 NORGESTREL

v/v of hydrochloric acid) and dichloromethane, centrifuge flow rate. 2 ml per minute,
and use the clear supernatant solution. spectrophotometer set at 275 nm,
Reference solution. A 0.15 per cent w/v solution of nOlj!oxacin
- injection volume. 20 fll.
RS in the same solvent mixture. lriject the test solution and the reference solution. The assay
is not valid unless the capacity factor is not less than 2, the
Apply to the plate 50 fll of each solution. After development,
dry the plate in air and examine in ultraviolet light at 254 nm. column efficiency is not less than 1500 theoretical plates, the
tailing factor for the norfloxacin peak is not more than 2.0 and
Theprincipal spot in the chromatogram obtained with the test
the relative standard deviation for replicate injections is not
solution corresponds to that in the chromatogram obtained
with the reference solution. more than 2.0 per cent.

B. In the Assay, the principal peak in the chromatogram Calculate the content ofCI6HIsFN303 in the tablets.
obtained with the test solution cOlTesponds to the peak due Storage. Store protected from light and moisture.
to norfloxacin in the chromatogram obtained with the reference
solution.

Tests Norgestrel
Dissolution (2.5.2).
Apparatus No.1,
Medium. 750 ml of acetate bufferpH4.0,
Speed and time. 50 rpm and 30 minutes.
Withdraw a suitable volume ofthe medium and filter. Measure
the absorbance of the filtrate, suitably diluted with acetate
buffer pH 4.0, if necessary, at the maximum at about 278 nm
(2.4.7). Concomitantly measure the abs.orbance of a solution Mol. Wt. 312.5
oflmown concentration of nOlj!oxacin RS in the same medium. Norgestrel is rac-13-ethyl-17-hydroxy-18,19-dinor-17Cf.,-
Calculate the total content ofCI6HIsFN303 in the medium. pregn-4-en-20-yn-3-one.
D. Not less than 70 per cent of the stated amount of Category. Progestogen.
C16HlsFN303. Dose. As a contraceptive, 150 to 300 flg in combination with
Other tests. Comply with the tests stated under Tablets. 20 to 50 flg ofethinyloestradiol daily.
Assay. Determine by liquid chromatography (2.4.14). Description. A white or almost white, clystalline powder;
Test solution. Weigh and powder 20 tablets. Add 80 ml ofthe practically odourless.
mobile phase to an accurately weighed quantity of the
Identification
powdered tablets containing about 100 mg ofNorfloxacin, mix
with the aid ofultrasound for 10 minutes, dilute with a 0.1 per A. Determine by infi'ared absorption spectrophotometry (2.4.6).
cent v/v solution of phosphoric acid to 200.0 ml and mix. Compare the spectTUm with that obtained with norgestrel RS.
Dilute 10.0 ml ofthis solution to 25.0 ml with the mobile phase, B. When examined in the range 220 nm to 360 111TI (2.4.7), a
mix and use the resulting solution after filtration through a 0.001 per cent w/v solution in methanol shows an absorption
filter with porosity ofnot more than 0.1 fllU. maximum only at about 240 nm.
Reference solution. A 0.02 per cent w/vsolution ofnOlj!oxacin
C. Melting range (2.4.21). 205° to 212°, but the range between
RS in the mobile phase. beginning and end of melting does not exceed 4°.
Chromatographic system
- a stainless steel colulUn 30 cm x 3.9 mm, packed with Tests
octadecylsilane bonded to porous silica (5 flm), Specific optical rotation (2.4.22). -0.1 ° to +0.1 0, determined in
mobile phase: 85 volumes ofa 0.1 per cent v/v solution a 5.0 per centw/v solution in chloroform.
of phosphoric acid and 15 volumes of acetonitrile,
- temperature. COlutm140° ± 1°, after preconditioning with Related substances. Determine by thin-layer chromatography
degassed 0.01 M sodium dihydrogen phosphate (2.4.17), coating the plate with silica gel G
adjusted to pH 4.0 with phosphoric acid flowing at a Mobile phase. A mixture of 80 volumes of dichloromethane
rate of0.5 ml per minute for 8 hours, and 20 volumes of ethyl acetate.

1795
NORGESTREL IP 2010

Test solution. Dissolve 0.2 g of the substance under Reference solution. A solution containing 0.06 per cent w/v
examination in 10 ml of chloroform. solution of norgestrel RS and 0.006 per cent w/v solution of
Reference solution (a). A 0.01 per cent w/v solution of the ethinyloestradiol RS.
substance under examination in chloroform. Apply to the plate 40 III of each solution. After development,
Reference solution (b). A 0.004 per cent w/v solution of the dry the plate in air, spray with ethanolic sulphuric acid
substance under examination in chloroform. (80 per cent v/v) ,heat at 110° for 10 minutes and examine in
ultraviolet light at 365 nm. The principal spots in the
Apply to the plate 10 III of each.solution. After development, chromatogram obtained with the test solution correspond to
dry the plate in air and spray with phosphomolybdic acid the spots for norgestrel (red fluorescence) and
solution. Any secondary spot in the chromatogram obtained ethinyloestradiol (orange-yellow fluorescence) in the
with the test solution is not more intense than the spot in the chromatogram obtained with the reference solution.
chromatogram obtained with reference solution (a) and not
more than two such spots are more intense than the spot in Tests
the chromatogram obtained with reference solution (b).
Uniformity of content. Comply with the test stated under
Sulphated ash. (2.3.18) Not more than 0.3 per cent. Tablets.
Loss on drying (2.4.19). Not more than 0.5 per cent, detennined Carry out the procedure described under Assay but using the
on 1.0 g by drying in an oven at 105° for 5 hours. following test solution.
Assay. Weigh accurately about 0.1 g, dissolve in sufficient Test solution. Add 2.0 ml of methanol (70 per cent) and 2.0 ml
ethanol (95 per cent) to produce 100.0 ml, dilute stepwise of a 0.00002 per cent w/v solution of diphenyl in methanol
with ethanol (95 per cent) to obtain a solution containing (70 per cent) (internal standard solution) to one tablet, shake
0.001 per cent w/v of levonorgestre1 and measure the for 20 minutes, centrifuge, filter the supernatant liquid through
absorbance of the resulting solution at the maximum at about a membrane filter with a pore size ofnot more than 0.2 mm and
241 nm, (2.4.7). Calculate the content of CZIHzsOz from the use the filtrate.
absorbance obtained with a 0.001 per cent w/v solution of
norgestrel RS in ethanol (95 per cent). Calculate the contents of norgestrel CZIHzsOz, and
ethinyloestradiol, CZOHZ40Z' in the tablet.
Storage. Store protected from moisture.
Other tests. Comply with the tests stated under Tablets.
Assay. Detennine by liquid chromatography (2.4.14) using the
Norgestrel and Etbinyloestradiol chromatographic system described under Uniformity of
content.
Tablets
Test solution. Weigh and powder 20 tablets. To a quantity of
Norgestrel and Ethinyloestradiol Tablets contain not less than the powder equivalent to one tablet add 2.0 ml of methanol
90.0 per cent and not more than 110.0 per cent of the stated (70 per cent) and 2.0 ml of a 0.00002 per cent w/v solution of
amounts of norgestrel, CZIHzsOz and ethinyloestradiol, diphenyl in methanol (70 per cent) (internal standard
CzOHZ40 Z. solution), shake for 20 minutes, centrifuge, filter the
Category. Oral contraceptive. supernatant liquid through a membrane filter with a pore size
afnot more than 0.2 mm and use the filtrate.
Dose. One tablet daily for 21 days starting from the fifth day of
menstrual cycle. Reference solution. A solution in methanol (70 per cent)
containing 0.15 mg per ml of norgestrel RS and 0.015 mg per
Usual strength. Norgestrel, 300 Ilg and Ethinyloestradiol, ml of ethinyloestradiol RS. Take 2.0 ml of this solution and
30 Ilg. add 2.0 ml of a 0.00002 per cent w/v solution of diphenyl in
Identification methanol (70 per cent) and use the resulting solution.

Detennine by thin-layer chromatography (2.4.17), coating the Chromatographic system


plate with silica gel G - a stainless steel column 15 cm x 4.6 rntD, packed with
octadecylsilane bonded to porous silica (5 to 7 Ilm),
Mobile phase. A mixture of 96 volumes of dichloromethane - mobile phase: a mixture of35 volumes of acetonitrile,
and 4 volumes of ethanol (95 per cent). 15 volumes of methanol and 45 volumes of water,
Test solution. Powder 20 tablets finely, triturate with 20 ml of - flow rate. 1 to1.5 ml per minute,
dichloromethane, allow the solids to sediment and use the - spectrophotometer set at 215 urn,
clear supernatant liquid. - injection volume. 20 Ill.

1796
IP 2010 NORTRIPTYLINE TABLETS

Inject the reference solution. The resolution between the two C. To about 50 mg dissolved in 3 ml ofwarm water, add 1drop
major peaks is not less 2.5 and the relative standard deviation of a 2.5 per cent w/v solution of quinhydrone in methanol; a
for replicate injections is not more than 2.0 per cent. red colour is produced after a few minutes (distinction from
Inject the test solution and the reference solution. The relative amitriptyline).
retention times are about 0.7 for ethinyloestradiol and about D. Gives the reactions ofchlorides (2.3.1).
1.0 for norgestrel.
Tests
Calculate the contents of norgestrel, C21H2S02, and
ethinyloestradiol, C2oH2402 in the tablets. Related substances. Determine by thin-layer chromatography
Storage. Store protected from light. (2.4.17), coating the plate with silica gel G
Mobile phase. A mixture of 85 volumes of cyclohexane,
15 volumes of ethyl acetate and 3 volumes of diethylamine.
Test solution. Dissolve 0.2 g of the substance under
Nortriptyline Hydrochloride examination in 10 ml of ethanol (95 per cent) prepared in
subdued light.
Reference solution. A 0.001 per cent w/v solution of
dibenzosuberone RS in ethanol (95 per cent) prepared in
, Hel subdued light.
Apply to the plate 5 III of each solution. Allow the mobile
phase to rise 14 cm in an unsaturated tank protected from
light. Dry the plate in air, spray with a freshly prepared solution
Mol. Wt. 299.8 of sulphuric acid containing 4 per cent v/v offormaldehyde
solution and examine immediately in ultraviolet light at
Nortriptyline Hydrochloride is 3-(10, II-dihydro-5H-dibenzo 365 nm. Any secondary spot in the chromatogram obtained
[a,dJcyclohept-5-ylidene)propyl(methyl)amine hydrochloride. with the test solution is not more intense than the spot in the
Nortriptyline Hydrochloride contains not less than 98.0 per chromatogram obtained with the reference solution.
cent and not more than 101.5 percent ofC ,9H2I N,HC1, calculated Heavy metals (2.3.13). 2.0 g complies with the limit test for
on the dried basis. heavy metals, Method B (10 ppm).
Category. Antidepressant.
Sulphated ash (2.3 .18). Not more than 0.1 per cent.
Dose. Initially, 50 to 150 mg daily; maintenance dose, 30 to 75
Loss on drying (2.4.19). Not more than 0.5 per cent, determined
mgdaily.
on 1.0 g by drying in an oven at 105° for 3 hours.
Description. A white to off-white powder; odour slight and
Assay. Weigh accurately about 0.25 g and dissolve in 25 ml of
characteristic.
anhydrous glacial acetic acid, warm slightly, if necessary, to
effect solution. Cool, add 5 ml of mercuric acetate solution.
Identification
Titrate with 0.1 M perchloric acid, determining the end-point
Test A may be omitted iftests B, C andD are carried out. Tests potentiometrically (2.4.25). Carry out a blank titration.
Band C may be omitted if tests A and, D are carried out. 1 ml of 0.1 M perchloric acid is equivalent to 0.02998 g of
A. Dissolve 0.1 gin 10 ml of water, make allmline with 1 M CI9H2I N,HCl.
sodium hydroxide, extract with 5 ml of chloroform and
Storage. Store protected from light and moisture.
evaporate to dryness using a current of nitrogen.
Determine by infrared absorption spectrophotometry (2.4.6).
Compare the spectrum with that obtained with nortriptyline
hyrdochloride RS treated in the same manner or with the Nortriptyline Tablets
reference spectrum ofnortriptyline.
Nortriptyline Hydrochloride Tablets
B. When examined in the range 230 nm to 360 nm (2.4.7), a
0.001 per cent w/v solution in methanol shows an absorption Nortriptyline Tablets contain less than 90.0 per cent and not
maximum only at about 239 nm; absorbance at about 239 nm, more than 110.0 per cent ofthe stated amount ofnortriptyline,
about 0.48. C I9H2I N. The tablets are coated.

1797
NORTRIPTYLINE TABLETS IP 2010

Usual strengths. The equivalent of 10 mgand 25mg of methanol and shake for 30 minutes. Add sufficient water to
nortriptyline. produce 10 ml, centrifuge and use the clear supernatant liquid.

Identification Reference solution. A 0.01 per cent w/v solution of


nortriptyline hydrochloride RS in methanol (50 per cent).
A. Shake a quantity ofthe powdered tablets containing about
Follow the procedure given in the Assay. Calculatethe content
5 mg ofnortriptyline with 20 ml of methanol and filter. To 1 ml
ofCzo Hz3 N in the tablet.
ofthe filtrate add 1 ml of a 2.5 per cent w/v solution of sodiurn
bicarbonate, 1 ml of a 2 per cent w/v solution of sodium Other tests. Comply with the tests stated under Tablets,
periodate and 1 ml ofa 0.3 per cent w/v solution ofpotassium Assay. Detennine by liquid chromatography (2.4.14).
permanganate. Allow to stand for 15 minutes, acidifY with
1 M sulphuric acid and extract with 10 ml of 2i2,4~ Test solution. Shake vigorously 20 tablets with 50 ml of water
trimethylpentane. until the tablets disintegrate completely, add 100.0 ml of
methanol and shake for 30 minutes. Add sufficient water to
When examined in the range 230 nm to 360 nm (2.4.7), the produce 200.0 ml, filter and dilute a volume of the filtrate
resulting trimethylpentane solution shows an absorption containing about 25 mg of nOltriptyline to 100.0 ml with
maximum only at about 265 nm. methanol (50 per cent).
B. Triturate a quantity of the powdered tablets containing Reference solution. A 0.025 per cent w/v solution of
0.1 g of nortriptyline with 10 ml of chloroform, filter and nortriptyline hydrochloride RS in methanol (50 per cent).
evaporate the filtrate to a low volume. Add ether until a
turbidity is produced and allow to stand. Dissolve 50 mg of Chromatographic system
the precipitate in 3 ml ofwann water, cool and add 1 drop ofa a stainless steel column 20 cm x 4.6 mm, packed with
2.5 per cent w/v solution of quinhydrone in methanol; a red octadecylsilane bonded to porous silica (l0 Ilm),
colour is produced after a few minutes (distinction from mobile phase: a 0.56 per cent w/v solution of sodium
amitriptyline): hexanesulphonate in a mixture of equal volumes of
water and acetonitrile adjusted to pH 4.5 with glacial
Tests acetic acid;
flow rate. 2 ml per minute,
Related substances. Detel1lline by thin71ayer chromatography - spectrophotometer set at 239 nm,
(2.4.17), coating the plate with silica gel G injection volume. 20 Ill.
Mobile phase. A mixture of 85 volumes of cyclohexane, Inject the test solution and the reference solution.
15 volumes of ethyl acetate and 3 volunies of diethylamine.
Calculate the content of C I9Hz1 N in the tablets.
Test solution. Extract a quantity of the powdered tablets
containing 20 mg of nortriptyline with 5 ml of a mixture of Storage. Store protected from light and moisture.
9 volumes of ethanol (95 per cent) and 1 volume of 2 M
hydrochloric acid, centrifuge and use the supernatant liquid.
Reference solution. A 0.001 per cent w/v solution of
dibenzosuberone RS in ethanol (95 per cent) prepared in Noscapine
subdued light. Narcotine
Apply to the plate 5 III of each solution. Allow the mobile
phase to rise 14 cm in an unsaturated tank protected from
light. Dry the plate in air, spray with a freshly prepared solution
of sulphuric acid containing 4 per cent v/v offormaldehyde
solution and examine immediately in ultraviolet light at
365 nm. Any secondary spot in the chromatogram obtained
with the test solution is not more intense than the spot in the
chromatogram obtained with the reference solution.
Uniformity of content (For tablets ~ontaining 10 mg or less).
Comply with the test stated under Tablets.
Detel1lline by liquid chromatography (2.4.14).
Test solution. Powder one tablet, add 2.5 ml of water, shake
vigorously to completely disperse the tablet, add 5 ml of Mol. Wt. 413.4

1798
IP 2010 NOSCAPINE

Noscapine is (38)-6,7-dimethoxy-3-[(5R)-5,6, 7,8-tetrahydro- Reference solution (c). Dissolve 1.5 mg of papaverine


4-methoxy-6-methyl-1 ,3-dioxolo[4,5-g]isoquinolin-5- hydrochloride in 10 ml ofthe test solution and dilute to 50 ml
yl]phthalide, an alkaloid obtained from opium. with the mobile phase.
Noscapine contains not less than 98.5 per cent and not more Chromatographic system
than 100.5 per cent ofC22H23N07, calculated on the dried basis. - a stainless steel column 12.5 cm x 4.6 mm, packed with
Category. Cough suppressant. nitrile groups chemically bonded to porous silica (5 11m),
- mobile phase: a mixture of35 volumes of methanol and
Dose. 15 to 30 mg three to four times daily. 65 volumes of phosphate buffer pH 6.0,
Description. Colourless crystals or a white crystalline powder. flow rate. I ml per minute,
- spectrophotometer set at 240 nm,
Identification - injection volume. 20 Ill.
Inject reference solution (c). The test is not valid unless the
Test A may be omitted iftests B, C andD are carried out. Tests
resolution between the peaks due to noscapine and papaverine
B, C and D may be omitted if test A is carried out.
(noscapine impurity A) is not less than 2.0. The relative
A. Determine by infrared absorption spectrophotometry (2.4.6). retention· time with reference to noscapine for noscapine
Compare the spectrum with that obtained with noscapine RS Impurity Ais about 1.3.
or with the reference spectrum of noscapine.
Inject the test solution, reference solution (a) and (b). Run the
B. When examined in the range 230 nm to 360 nm (2.4.7), a
chromatogram 2.5 times the retention time of the principal
0.005 per cent w/v solution in methanol shows absorption
peak. In the chromatogram obtained with the test solution the
maxima at about 291 nm and 310 nm; ratio ofabsorbance at the
area ofthe peak due to noscapine impurity A is not more than
maximum at about 310 nm to that at the maximum at about
the area ofthe principal peak in the chromatogram obtained
291 nm, 1.2 to 1.3.
with reference solution (b) (0.5 per cent), the area ofthe any
C. To 0.1 g in a porcelain dish add a few drops of sulphuric oth~r secondary peak is not more than 0.4 times the area of
acid and stir; a greenish-yellow solution is formed which on the principal peak in the chromatogram obtained with reference
warming becomes red and finally violet. solution (a) (0.2 per cent), and the sum of the areas of
D. Dissolve 50mg inS mlof5 Mhydrochloricacid, add 10ml secondary peaks other than noscapine impurity A is not more
of a mixture of equal volumes of ethanol (95 per cent) and a than the area of the principal peak in the chromatogram
saturated solution of sodium acetate, mix and allow to stand obtained with reference solution (a) (0.5 per cent). Ignore any
for about 3 minutes; shining crystals separate. peak with an area less than 0.1 times the area of the principal
peak in the chromatogram obtained with reference solution
Tests (a) (0.05 per cent).

Appearance ofsolution. A 2.0 per cent w/v solution in acetone Morphine. Dissolve 0.1 gin 10 m1 of 0.1 M hydrochloric acid.
examined immediately after preparation is clear (2.4.1), and not To 1 m1 of the resulting solution add a mixture of 1 ml of
more intensely coloured than reference solution YS6 (2.4.1). potassium ferricyanide solution, 0.05 m1 of ferric chloride
test solution and 4 m1 of water; no blue or dark green colour
Specific optical rotation (2.4.22). +42.0° to +48.0°, determined
develops within 1 minute.
at 20° in a solution prepared by dissolving 0.5 g in sufficient
0.1 M hydrochloric acid to produce 25.0 ml. Sulphated ash (2.3.1 8). Not more than 0.1 per cent.
Related substances: Determine by liquid chromatography
(2.4.14). Loss on drying (2.4.19). Not more than 1.0 per cent, determined
on 1.0 g by drying in an oven at 105°.
Test solution. Dissolve 20 mg of the substance under
examination with gentle heating in 14 ml of methanol, cool, Assay. Weigh accurately about 0.35 g, dissolve in 40 m1 of
and dilute to 20 ml with phosphate buffer solution pH 6.,0. anhydrous glacial acetic acid, warming gently. Titrate with
Reference solution (a). Dilute 1.0 ml of the test solution to 0.1 M perchloric acid, determining the end-point
20.0 ml with the mobile phase. Dilute 1.0 ml ofthe solution to potentiOluetrically (2.4.25). Carry out a blank titration.
10.0 ml with the mobile phase.
1 m1 of0.1 M perchloric acid is equivalentto 0.04134 g of
Reference solution (b). Dissolve 5 mg of papaverine C22H23N07•
hydrochloride in 50 ml of the test solution. Dilute 1.0 ml of
this solution to 20 ml with the mobile phase. Storage. Store protected from light and moisture.

1799
NOSCAPINE LINCTUS IF 2010

Noscapine Linctus Novobiocin Sodium


Narcotine Linctus
Noscapine Linctus is a solution of Noscapine in a suitable
flavoured vehicle. It may contain up to 1per cent w/v solution
ofCitric Acid.
Noscapine Linctus contains not less than 90.0 per cent and
not more than 110.0 per cent of the stated amount of
noscapine, C22H23N07'
Usual strength. 7 mg per 5 ml.
Mol. Wt. 634.6
Identification Novobiocin Sodium is the monosodium salt of novobiocin,
N-[7- {3-0-( aminocarbonyl)-6-deoxy-5-C-methyl-4-0-methyl-
To a quantity containing 60 mg ofNoscapine add 20 ml of
~-L-Iy.xo-hexopyranosyl}-oxy-4-hydroxy-8-methyl-2-oxo-2H­
water, 2 g of sodium chloride and 2 ml of 5 M sodium
I-benzopyran-3-yl]-4-hydroxy-3-(3-methyl-2-
hydroxide. Extract with successive quantities of50, 50, 25 and
butenyl)benzamide, an antimicrobial substance produced by
25 ml ofether. Combine the extracts, wash with three quantities,
the growth of certain strains of Streptomyces niveus or
each of5 ml, of water and evaporate to dryness. Dissolve the
related organisms or by other means.
residue in 20 ml of chloroform. Wash with three quantities,
each of20 ml, of water, dry the chloroform layer with anhydrous Novobiocin Sodium contains the equivalent of not less than
sodium sulphate, filter and evaporate the solvent. Ifnecessary, 850 Ilg of novobiocin per mg, calculated on the dried basis.
induce crystallisation by scratching with a glass rod. The Category. Antibacterial.
crystals comply with the following tests.
Dose. The equivalent of 1 to 2 g ofnovobiocin daily, in divided
A. Determine by infrared absorption spectrophotometry (2.4.6). doses.
Compare the spectrum with that obtained with noscapine RS
or with the reference spectrum of noscapine. Description. A white or yellowish white, crystalline powder.
B. When examined in the range 230 nm to 360 nm (2.4.7), a Identification
0.005 per cent w/v solution in methanol shows absorption
maxima at about 291 nmand 310 nm; ratio ofabsorbance at the A. Determine by thin-layer chromatography (2.4.17), coating
maximum at about 310 nm to that at the maximum at about the plate with silica gel G. .
291 nm, 1.2 to 1.3. Mobile phase. A mixture of 75 volumes of chloroform,
25 volumes of methanol and 1 volume of strong ammonia
Tests solution.
Other tests. Complies with the tests stated under Oral Liquids. Test solution. Dissolve a quantity of the substance under
examination in methanol so as to obtain a solution containing
Assay. Weigh accurately a quantity containing 60 mg of
0.1 per cent w/v solution of novobiocin.
Noscapine, add 20 ml of water, 2 g of sodium chloride and
2 ml of 5 M sodium hydroxide and extract with successive Reference solution. A 0.1 per cent w/v solution of novobiocin
quantities of50, 50,25 and 25 ml ofether. Combine the extracts, RS in methanol.
wash with three quantities, each of5 ml, of water and evaporate Apply to the plate 1 III of each solution. After development,
to dryness. To the residue add 50.0 ml of 0.1 M hydrochloric dry the plate in air and examine in ultraviolet light at 254 nm.
acid, warm on a water-bath to dissolve and to remove any The principal spot in the chromatogram obtained with the test
traces ofether and dilute to 100.0 ml with water. Dilute 3.0 ml solution corresponds to that in the chromatogram obtained
to 50.0 ml with water and measure the absorbance of the with the reference solution.
resulting solution at the maximum at about 310 nm (2..4.7).
Calculate the content ofC22H23N07 taking 90.7 as the specific B. When examined in the range 230 nm to 360 nm (2.4.7), a
absorbance at 310 nm. 0.001 per cent w/v solution in a 0.4 per cent w/v solution of
potassium hydroxide shows an absorption maximum only at
Determine the weight per ml ofthe linctus (2.4.29), and calculate about 307 nm.
the content ofC22H23N07, weight in volume.
C. The residue obtained by igniting it gives the tests for sodium
Storage. Store protected from light and moisture. salts (2.3~ 1).

1800
IP 2010 NYSTATIN

Tests Dose. In the treatment of alimentary candidiasis, 500,000 to


1,000,000 Units daily, in divided doses.
pH (2.4.24).6.6 to 8.5, determined in a 2.5 percentw/v solution.
Description. A yellow to slightly brown powder; odour,
Specific optical rotation (2.4.22). -50.0° to-58.0°, determined characteristic; hygroscopic.
in a 5.0 per cent w/v solution in methanol containing I per
cent v/v of hydrochloric acid. Identification
Loss on drying (2.4.19). Not more than 6 per cent, determined A. When examined in the range 220 nm to 360 nm (2.4.7), the
on 0.2 g by drying in an oven at 60° over phosphoruspentoxide final solution obtained in the test for Light absorption shows
at a pressure not exceeding 0.7 kPa for 3 hours. absorption maxima at about 230 nm, 291 nm, 305 nm and
Assay. Determine by the microbiological assay ofantibiotics, 319 nm. The ratios of the absorbances at the maxima at about
Method A (2.2.1 0), and express the results in J.lg ofnovobiocin 291 nm and about 319 nm to the absorbance at the maximum at
per mg. about 305 nm are 0.61 to 0.73 and 0.83 to 0.96, respectively.
Use as the blank a solution prepared in the same manner
Novobiocin Sodium intended for use in the manufacture of
without the substance under examination.
Parenteral Preparations complies with the following
additional requirements. B. Shake 30 mg with 5 ml of water for 2 minutes, add 2 ml of
sodium molybdotungstophosphate solution, and allow to
Bacterial endotoxins (2.2.3). Not more than 0.7 Endotoxin units
stand for I hour; the green colour produced is darker than
per mg.
that produced by repeating the test without the substance
Sterility. Complies with the test for sterility (2.2.11). under examination.
Storage. Store protected from light and moisture at a C. Shake 30 mg with 5 ml of water for 2 minutes, add 2 ml ofa
temperature not exceeding 30°. If it is intended for use in the solution prepared by dissolving 0.1 g ofpyrogallol in 100 ml
manufacture of parenteral preparations, the container should of decolorised magenta solution, heat on a water-bath until a
be sterile and sealed so as to exclude micro-organisms. dark pink colour is produced, cool and allow to stand for
Labelling. The label states whether or not the contents are 1 hour; the pink colour is retained.
intended for use in the manufacture ofparenteral preparations. D. To 2 mg add 0.1 ml of hydrochloric acid; a brown colour is
produced.
E. To 2 mg add 0.1 ml of sulphuric acid; a brown colour is
Nystatin produced which becomes violet on standing.

Tests
pH (2.4.24). 6.5 to 8.0, determined in a 3.0 per cent w/v
OH suspension in water.
Light absorption (2.4.7). Dissolve 0.1 g in a mixture of5.0 ml of
COOH
glacial acetic acid and 50 ml of methanol, add sufficient
methanol to produce 1 00.0 ml and dilute 1.0 ml ofthe resulting
o solution to 100.0 ml with methanol. Absorbance ofthe resulting
\--o-\CH 3 solution, measured within 30 minutes of preparation, at the
~OH maximum at about 305 nm, not less than 0.60. Use as the blank
OH NH 2 a solution prepared in the same manner without the substance
under examination.
Mol. Wt. 926.1 Composition. Determine by liquid chromatography (2.4.14).
Nystatin is an antifungal substance produced by the growth Note-Carry out the test protectedfrom light.
of certain strains of Streptomyces noursei or by any other Test solution. Dissolve 20 mg of the substance under
means. It consists mainly ofpolyenes, the principal component examination in 50 ml of dimethyl sulphoxide.
being nystatin AI.
Reference solution (a). A 0.04 per cent w Iv solution of nystatin
Nystatin has a potency of not less than 4400 Units per mg, RS in dimethyl sulphoxide.
calculated on the dried basis.
Reference solution (b). Dissolve 20 mg ofthe substance under
Category. Antifungal. examination in 25 ml ofthe methanol and dilute to 50 ml with

1801
NYSTATIN IP 2010

water. To 10.0 ml of this solution add 2.0 ml of dilute Determine by the microbiological assay ofantibiotics (2.2.10).
hydrochloric acid. Allow to stand at room temperature for 1
Nystatin intendedfor oral administration complies with the
hour.
following additional requirement.
Reference solution (c). Dilute 1.0 ml of reference solution (a)
Abnormal toxicity (2.2.1). Complies with the test for abnormal
in 100.0 rnl of dimethyl sulphoxide. Dilute 1.0 rnl ofthis solution
toxicity, using a quantity containing not less than 600 Units
to 10.0 ml with dimethyl sulphoxide.
suspended in not more than 0.5 ml ofa 0.5 per centw/v solution
Chromatographic system of acacia and injecting the suspension intraperitoneally.
- a stainless steel column 15 cm x 4.6 mm, packed with
Storage. Store protected from light and moisture.
base-deactivated end-capped octadecylsilane bonded
to porous silica (5 /lm), Labelling. The label states the strength in terms ofthe number
- mobile phase: A. a mixture of29 volumes ofacetonitrile of Units ofNystatin per mg.
and 71 volumes of 0.385 per cent w/v solution of
ammonium acetate,
B. a mixture of 40 volumes of 0.385 per
cent w/v solution ofammonium acetate and 60 volumes
Nystatin Ointment
of acetonitrile. Nystatin Ointment is a dispersion of Nystatin in microfine
- a linear gradient programme using the conditions given powder in a suitable ointment basis.
below,
Nystatin Ointment contains not less than 90.0 per cent and
- flow rate. 1 ml per minute,
not more than 130.0 per cent ofthe stated number ofUnits of
- spectrophotometer set at 305 nm,
nystatin.
- injection volume. 20 /ll.
Time Mobile phase A Mobile phase B Usual strength. 100,000 Units per g.
(in min.) (per cent w/v) (per cent w/v)
Identification
0-25 100 o
25-35 100-0 0-100 Disperse a quantity containing 25,000 Units in 10 ml of
35-45 0 100 chloroform, add 40 ml ofmethanol and shake. Filter and dilute
1 ml ofthe filtrate to 25 ml with methanol.
45-50 0-100 100-0
50-55 100 o When examined in the range 230 nm to 360 nm (2.4.7), the
Inject reference solution (b). The test is not valid unless the resulting solution shows absorption maxima at about 291 nm,
resolution between the two principal peaks is not less than 305 nm and 319 nm. The ratios ofthe absorbances at the maxima
3.5. at about 291 nm and about 319 nm to the absorbance at the
maximum at about 305 nm are 0.61 to 0.73 and 0.83 to 0.96,
Inject the test solution, reference solution (a) and (c). In the
respectively. Use as the blank a solution prepared exactly in
chromatogram obtained with the test solution the area of the
the same manner without the substance under examination.
peak due to nystatin A 1 is not less than 85 per cent the area of
the plincipal peak in the chromatogram obtained with reference Tests
solution (a), the area of the any other compound is not more
than 4.0 per cent the area of the principal peak in the Other tests. Complies with the tests stated under Ointments.
chromatogram obtained with reference solution (a). Ignore Assay. Protect the solution from light throughout the assay.
any peak with a retention time of less than 2 minutes.
Weigh accurately a quantity containing 400,000 Units, disperse
Heavy metals (2.3.13). 1.0 g complies with the limit test for in 20 ml of ether in a stoppered flask, add 70 ml of
heavy metals, Method B (20 ppm). dimethylformamide, shake for a few minutes, add 10 ml of
Sulphated ash (2.3.18). Not more than 3.5 per cent. water, shake vigorously for a few minutes and add sufficient
dimethylformamide to produce 100.0 ml. Mix well, filter and
Loss on drying (2.4.19). Not more than 5.0 per cent, determined
dilute 10.0 ml of the filtrate to 100.0 ml with buffer solution
on 1.0 g by drying in an oven at 60° at a pressure not exceeding
No 4 (2.2.10).
0.1 kPa for 3 hours.
Determine by the microbiological assay ofantibiotics (2.2.10).
Assay. Protect the solution from light throughout the assay.
Storage. Store protected from moisture.
Weigh accurately about 75 mg and dissolve in sufficient
dimethylformamide to produce 50.0 ml; dilute 10.0 ml of the Labelling. The label states the strength in terms ofthe number
resulting solution to 200.0 rnl with buffersolutionNo4 (2.2.10). of Units of Nystatin per g.

1802
IP 2010 NYSTATIN TABLETS

Nystatin Pessaries Nystatin Tablets


Nystatin Vaginal Tablets Nystatin Tablets contain not less than 90.0 per cent and not
Nystatin Pessaries contain not less than 90.0 per cent and not more than 130.0 per cent of the stated number of Units of
more than 130.0 per cent of the stated number of Units of nystatin. The tablets are coated.
nystatin. Usual strength. 500,000 Units.
Usual strength. 100,000 Units.
Identification
Identification Extract a quantity of the powdered tablets containing
Extract a quantity of the powdered pessaries containing 300,000 Units with a mixture of50 ml of methanol and 5 ml of
300,000 Units with a mixture of50 ml of methanol and 5 ml of glacial acetic acid, add sufficient methanol to produce
glacial acetic acid, add sufficient methanol to produce 100 ml and filter. Dilute 1 ml of the filtrate to 100 ml with
100 ml and filter. Dilute 1 ml of the filtrate to 100 ml with methanol. The resulting solution complies with the follwing
methanol. The resulting solution complies with the follwing test.
test. When examined in the range 230 nm to 360 nm (2.4.7), the
Disperse a quantity containing 25,000 Units in 10 ml of solution shows absorption maxima at about 291 nm, 305 nm
chlor%nn, add 40 ml of methanol and shake. Filter and dilute and 319 urn. The ratios of the absorbances at the maxima at
1 ml ofthe filtrate to 25 ml with methanol. about 291 nm and about 319 nm to the absorbance at the
maximum at about 305 nm are 0.61 to 0.73 and 0.83 to 0.96,
When examined in the range 230 urn to 360 urn (2.4.7), the respectively. Use as the blank a solution prepared exactly in
resulting solution shows absorption maxima at about 291 urn, the same manner without the substance under examination.
305 urn and 319 urn. The ratios ofthe absorbances at the maxima
at about 291 urn and about 319 nm to the absorbance at the Tests
maximum at about 305 urn are 0.61 to 0.73 and 0.83 to 0.96,
respectively. Use as the blank a solution prepared exactly in Disintegration (2.5.1). 30 minutes, but using a 0.6 per cent
the same manner without the substance under examination. v/v solution of hydrochloric acid in place of water. If the
tablets fail to disintegrate, wash them rapidly by immersion in
Tests water and continue the test using phosphate buffer pH 6.8;
the tablets then disintegrate within a further 30 minutes.
Other tests. Comply with the tests stated under Pessaries.
Loss on drying (2.4.19). Not more than 5 per cent, determined Loss on drying (2.4.19). Not more than 5.0 per cent, determined
on 1.0 g ofthe powdered pessaries by drying in an oven at 60° on 1.0 g ofthe powdered tablets by drying in an oven at 60° at
at a pressure not exceeding 0.7 kPa for 3 hours. a pressure not exceeding 0.7 kPa for 3 hours.

Assay. Protect the solution from light throughout the assay. Other tests. Comply with the tests stated under Tablets.

Weigh and powder 20 pessaries. Weigh accurately a quantity Assay. Weigh and powder 20 tablets. Weigh accurately a
ofthe powder containing 200,000 Units and shake with 50.0 ml quantity of the powder containing 200,000 Units and shake
of dimethylfonnamide for 1 hour. Centrifuge, dilute 10.0 ml of with 50.0 ml of dimethylfonnamide for 1 hour. Centrifuge, dilute
the clear, supernatant liquid to 200.0 ml with buffer solution 10.0 ml ofthe clear, supernatant liquid to 200.0 ml with buffer
No 4 (2.2.10). solution No 4 (2.2.10).
Determine by the microbiological assay ofantibiotics (2.2.10). Determine by the microbiological assay ofantibiotics (2.2.10).
Storage. Store protected from light and moisture. Storage. Store protected from moisture.
Labelling. The label states the strength in terms ofthe number Labelling. The label states the strength in tenns ofthe number
of Units ofNystatin. of Units of Nystatin.

1803
INDIAN PHARMACOPOEIA 2010 MONOGRAPHS

0
Oestradiol Benzoate 1807
Oestradiol Injection 1807
Ofloxacin 1808
Ofloxacin Infusion 1809
Ofloxacin Opthalmic Solution 1809
Ofloxacin Tablets 1810
Olanzapine 1811
Olanzapine Tablets 1812
Oleic Acid 1812
Omeprazole 1813
Omeprazole Capsules 1814
Ondansetron Hydrochloride 1815
Ondansetron Injection 1816
Ondansetron Orally Disintegrating Tablets 1816
Ondansetron Oral Solution 1818
Ondansetron Tablets 1819
Oral Rehydration Salts 1820
Ormeloxifene Hydrochloride 1821
Ormeloxifene Hydrochloride Tablets 1822
Ornidazole 1823
Ornidazole Tablets 1824
Orphenadrine Citrate 1825
Orphenadrine Hydrochloride 1826
Orphenadrine Tablets 1827
OseltamivirPhosphate 1827
Oseltamivir Capsules 1828
Oseltarnivir Oral Suspension 1829
Oxazepam 1830
Oxazepam Tablets 1831
Oxcarbazepine 1832

1805
MONOGRAPHS INDIAN PHARMACOPOEIA 2010

Oxcarbazepine Tablets 1833


Oxprenolol Hydrochloride 1834
Oxprenolol Tablets 1834
Oxygen 1835
Oxygen 93 Per cent 1835
Oxytetracycline Dihydrate 1836
Oxytetracycline Injection 1838
Oxytetracycline Hydrochloride 1838
Oxytetracycline Capsules 1840
Oxytetracycline Eye Ointment 1841
Oxytetracycline Hydrochloride Injection 1842
Oxytocin 1842
Oxytocin Injection 1845
Oxytocin Nasal Solution 1846

1806
IP 2010 OESTRADIOL INJECTION

Oestradiol Benzoate Test solution (a). Dissolve 0.2 g of the substance under
examination in 10 ml ofa mixture of90 volumes of chloroform
and 10 volumes of methanol.
Test solution (b). Dissolve 0.1 g of the substance under
examination in 100 ml ofthe same solvent mixture.

o Reference solution (a). A 0.02 per cent w/v solution of the

~O
substance under examination in the same solvent mixture.
Reference solution (b). A 0.1 per cent w/v solution of
oestradiol benzoate RS in the same solvent mixture.
Apply to the plate 5 III of each solution. After development,
Mol. Wt. 376.5 dry the plate in air until odour of the solvent is no longer
Oestradiol Benzoate is 17~-hydroxyestra-1 ,3,5(1 0)-trien-3-yl detectable, heat at 1100 for 10 minutes, spray the plate while
benzoate. hot with ethanolic sulphuric acid (20 per cent), heat again at
1100 for 10 minutes and examine in ultraviolet light at 365 nm.
Oestradiol Benzoate contains not less than 97.0 per cent and Any secondary spot in the chromatogram obtained with test
not more than 103.0 per cent ofC2sH2s03, calculated on the solution (a) is not more intense than the spot in the
dried basis. chromatogram obtained with reference solution (a).
Category. Oestrogen. Sulphated ash (2.3.18). Not more than 0.2 per cent, determined
Dose. By intramuscular injection, I to 2 mg daily. on 0.5 g.
Description. Colourless crystals or a white, crystalline powder; Loss on drying (2.4.19). Not more than 0.5 per cent, determined
odourless. on 0.5 g by drying in an oven at 105 0 for 3 hours.
Assay. Weigh accurately about 25 mg, dissolve in sufficient
Identification
ethanol (95 per cent) to produce 250.0 ml. Dilute 10.0 ml to
Test A may be omitted if tests Band C are carried out. Test C 100.0 ml with ethanol (95 per cent) and measure the
may be omitted if tests A and B are carried out. absorbance ofthe resulting solution at the maximum at about
231 nm (2.4.7). Calculate the content ofC2sH2s03 taking 500 as
A. Determine by infrared absorption spectrophotometry (2.4.6).
the specific absorbance at 231 nm.
Compare the spectrum with that obtained with oestradiol
benzoate RS or with the reference spectrum of oestradiol Storage. Store protected from light and moisture.
benzoate.
B. In the test for Related substances, the principal spot in the
chromatogram obtained with test solution (b) corresponds to
that in the chromatogram.obtained with reference solution (b) Oestradiol Injection
when examined in daylight and in ultraviolet light at 365 nm.
Oestradiol Benzoate Injection
C. To about 1 mg add 0.5 ml of a 5 per cent w/v solution of
Oestradiol Injection is a sterile solution ofOestradiol Benzoate
ammonium molybdate in sulphuric acid; a yellowish green
in Ethyl Oleate or other suitable ester, in a suitable fixed oil or
colour develops which exhibits an intense green fluorescence
in any mixture of these. It may contain suitable alcohols.
when examined in ultraviolet light at 365 nm. Add 1 illl of
sulphuric acid and 9 ml of water; the solution becomes pink Oestradiol Benzoate Injection contains not less than 90.0 per
with a yellowish fluorescence. cent and not more than 110.0 per cent ofthe stated amount of
oestradiol benzoate, C2sH2S03'
Tests Usual strength. 1 mg per ml.
0 0
Specific optical rotation (2.4.22). +57.0 to +63.0 , determined
in a 1.0 per cent wN solution in dioxan. Identification
Related substances. Determine by thin-layer chromatography Determine by thin-layer chromatography (2.4.17), coating the
(2.4.17), coating the plate with silica gel G plate with silica gel G.
Mobile phase. A mixture of 90 volumes of toluene and Mobile phase. A mixture of 80 volumes of toluene and
10 volumes of ethanol (95 per cent). 20 volumes of ethyl acetate.

1807
OESTRADIOL INJECTION IP 2010

Test solution. Add 10 ml of2, 2, 4-trimethylpentane to a volume Labelling. The label states (1) the nature and composition of
of the injection containing 2 mg of Oestradiol Benzoate and the solvent; (2) that it is meant for intramuscular injection
extract with three quantities, each of 10 ml, of ethanol (70 per only; (3) that any solid matter that may have separated on
cent). Wash the combined extracts with 15 ml of 2,2,4- standing should be redissolved by warming before use.
trimethylpentane, evaporate the ethanolic extract to dryness
using a rotary evaporator and dissolve the residue in 2 ml of
chloroform. Ofloxacin
Reference solution. A 0.1 per cent w/v solution of oestradiol
benzoate RS in chloroform.
Apply to the plate 5 f.!l of each solution. After development,
dry the plate in air, spray with ethanolic sulphuric acid
(20 per cent), heat at 105° for 10 minutes and examine in
ultraviolet light at 365 nm. The principal spot in the
chromatogram obtained with the test solution corresponds to
that in the chromatogram obtained with the reference solution. Mol. Wt. 361.4

Tests Ofloxacin is (RS)-9- fluoro-3-methyl-l0-(4-methylpiperazin-l-


yl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3,-de]-1 ,4-benzoxazine-
Other tests. Complies with the tests stated under Parenteral 6-carboxylic acid
Preparations (Injections).
Ofloxacin contains not less than 98.5 per cent and not more
Assay. Determine by liquid chromatography (2.4.14). than 101.5 per cent of ClsH2oFN304. calculated on the dried
Test solution (a). Dilute an accurately measured quantity of basis.
the injection containing about 1 mg of Oestradiol Benzoate to Category. Antibacterial.
10.0 ml with a mixture of 90 volumes of cyclohexane and
10 volumes of dioxan. Dose. 200 to 400 mg daily.

Test solution (b). Add 1 ml ofa solut~on prepared by dissolving Description. A pale yellow or bright yellow, cryst~lline powder.
15 mg of 4-hydroxybenzaldehyde (internal standard) in Identification
10.0 ml of dioxan, adding sufficient cyclohexane to produce
100.0 ml (solution A), to an accurately measured quantity of Determine by infrared absorption spectrophotometry (2.4.6).
the injection containing about 1 mg of Oestradiol Benzoate Compare the spectrum with that obtained with ofloxacin RS
and dilute to 10.0 ml with sufficient ofa mixture of90 volumes or the spectrum obtained with the reference solution.
of cyclohexane and 10 volumes of dioxan.
Tests
Reference solution. Add 10 ml of solution A to 10 mg of
oestradiol benzoate RS, accurately weighed, and dilute to Light absorption. Absorbance at 440 urn (2.4.7), of0.5 per cent
100.0 ml with the same solvent mixture. w/v solution in 0.1 M hydrochloric acid is not more than 0.25.

Chromatographic system Related substances. Determine by liquid chromatography


- a stainless steel column 30 cm x 4 mm, packed with porous (2.4.14).
silica particles{1O f.!m), Test solution. Dissolve 10 mg of the substance under
- mobile phase: 90 volumes of cyclohexane and examination in 10 ml of methanol.
10 volumes of dioxan,
Reference solution (a). A 0.1 per cent w/v solution of
- flow rate. 2 ml per minute,
ofloxacin RS in methanol.
- spectrophotometer set at 254 nm,
- injection volume. 20 f.!l. Reference solution (b). Dilute I ml ofreference solution (a) to
100 ml with methanol.
Inject test solutions (a), (b) and the reference solution. The
assay is not valid unless the resolution between the peaks Chromatographic system
due to benzyl alcohol (ifpresent) and oestradiol benzoate and - a stainless steel column 10 cm x 4.6 mm packed with
between the peaks due to oestradiol benzoate and the internal octadecylsilane bonded to porous silica (5 f.!m),
standard is more than 1.5. mobile phase: a mixture of 10 volumes of acetonitrile
and 90 volumes ofphosphate bufferpH 2.4 prepared by
Calculate the content of C2sH2s03 in the injection.
dissolving 27.2 g of monobasic potassium phosphate
Storage. Store protected from light. in 1000 ml of water, adjust the pH to 2.4 with

1808
IP 2010 OFLOXACIN OPHTHALMIC SOLUTION

orthophosphoric acid, NOTE -Protect the solutions from the light.


- flow rate. 2 ml per minute,
Test solution. Measure accurately a volume containing 50 mg
- spectrophotometer set at 294 nm,
ofOfloxacin in 100.0 ml with mobilephase. Dilute 5.0 ml ofthe
- injection volume. 10 fll.
solution to 50.0 ml with mobile phase.
Inject reference solution (b). The test is not valid unless the
Reference solution. A 0.005 per cent w/v solution of ojloxacin
column efficiency in not less than 1400 theoretical plates.
RS in mobile phase.
Inject the test solution and reference solution (b). Run the
Chromatographic system
chromatogram three times of the principal peak. In the
- a stainless steel column 25 cm x 4.6 mm packed with
chromatogram obtained with the test solution, the area of any
octadecylsilane bonded to porous silica (5 flm),
secondary peak is not more than 0.5 times the area ofthe peak
- mobile phase: a mixture of80 volumes ofbuffer solution
in the chromatogram obtained with reference solution (b) (0.5
prepared by dissolving 6.8 g of potassium dihydrogen
per cent) and the sum of areas of all the secondary peaks is
orthophosphate and 0.47 g sodium 1-hexane
not more than the area of the peak in the chromatogram
sulphonate in 1000 ml of water, add 1 ml of triethylamine
obtained with the reference solution (b) (1.0 per cent).
and adjust the pH to 3.0 with orthophosphoric acid
Heavy Metals (2.3.13). 2.0 g complies with the limit test for and 20 volumes of acetonitrile,
heavy metals, Method B (l0 ppm). - flow rate. 1 ml per minute,
Sulphated ash (2.3.18). Not more than 0.1 per cent. - spectrophotometer set at 294 nm,
Loss on drying (2.4.19). Not more than 0.2 per cent, determined - injection volume. 20 fll.
on 1.0 g by drying in an oven at 105° for 4 hours. Inject the reference solution. The test is not valid unless the
Assay. Weigh accurately about 0.3 g, dissolve in 100 ml of tailing factor is not more than 2.0 and the relative standard
anhydrous glacial acetic acid. l)trate with 0.1 M perchloric deviation for replicate injections is not more than 2.0 per cent.
acid, determining the end-point potentiometrically (2.4.25). Inject the test solution and the reference solution.
Carry out a blank titration.
Calculate the content ofClsH2oFN304 in infusion.
1 ml of 0.1 M perchloric acid is equivalent to 0.03614 g of
ClsH20FN304.
Storage. Store protected from light and moisture. Ofloxacin Ophthalmic Solution
Ofloxacin Ophthalmic Solution is a sterile aqueous solution of
Ofloxacin.
Ofloxacin Infusion
Ofloxacin Ophthalmic Solution contains not less than 90.0 per
Ofloxacin Infusion is a sterile solution of Ofloxacin in 5 per cent and not more than 110.0 per cent of the stated amount of
cent Dextrose Injection or in Sodium Chloride Injection. ofloxacin, ClsH20FN304.
Ofloxacin Infusion contain not less than 90.0 per cent and not Usual strength. 0.3 per cent w/w.
more than 120.0 per cent of the stated amount of ofloxacin,
ClsH20FN304' Identification
Usual strengths. 25 mg; 50 mg; 100 mg; 200 mg; 400mg. In the Assay, the principal peak in the chromatogram obtained
with the test solution corresponds to the peak in the
Identification chromatogram obtained with the reference solution.
In the Assay, the principal peak in the chromatogram obtained Tests
with the test solution corresponds to the peak in the
chromatogram obtained with the reference solution. pH (2.4.24).6.0 to 7.2.
Sterility (2.2.11). Comply with the test for sterility.
Tests
Assay. Determine by liquid chromatography (2.4.14).
pH (2.4.24). 3.8to 7.5.
Solvent mixture. Phosphate buffer pH 7.25 prepared by
Other tests. Complies with the tests stated under Parenteral
dissolving 3.56 g of disodium hydrogen phosphate in 1000 ml
Preparation (Infusions).
water, adjusted pH to 7.25 using orthophosphoric acid or
Assay. Determine by liquid chromatography (2.4.14). sodium hydroxide solution.

1809
OFLOXACIN TABLETS IP 2010

Test solution. Measure accurately a volume of Opthalmic obtained from a solution of known concentration of
Solution, containing 30 mg ofOfloxacin in 100.0 ml ofsolvent ojloxacin RS in the same medium.
mixture. Dilute 1.0 ml of the solution to 10.0 with solvent
D. Not less than 75 per cent of the stated amount of
mixture.
ClsH20FN304.
Reference solution. A 0.003 per cent w/v solution of ojloxacin Related substances. Determine by liquid chromatography
RS in solvent mixture. (2.4.14).
Chromatographic system Test solution. Weigh and powder 20 tablets. Weigh accurately
- a stainless steel column 15 cm x 4.6 mm packed with a quantity ofpowdered tablet containing 100 mg ofOfloxacin,
octadecylsilane bonded to porous silica (5 !Jm) (Such disperse in 60 ml of methanol and dilute to 100 ml with methanol
as TSK GEL), . and filter.
- mobile phase: a mixture of 20 volumes of acetonitrile,
80 volumes of phosphate buffer pH 7.25 prepared by
Reference solution (a). A 0.1 per cent w/v solution of
dissolving 2.54 g of tetrabutyl ammonium hydrogen
ojloxacin RS in methanol.
sulphate and 3.56 g of disodium hydrogen phosphate Reference solution (b). Dilute 1 ml ofreference solution (a) to
in 1000 ml water, 100 ml with methanol.
- flow rate. 1.5 ml per minute, Chromatographic system
- spectrophotometer set at 294 nm, a stainless steel column 15 cm x 4.6 mmpacked with
- injection volume. 20 !Jl. octadecylsilane bonded to porous silica (5 !Jm),
Inject the reference solution. The test is not valid unless the - mobile phase: a mixture of 8 volumes of acetonitrile
relative standard deviation for replicate injections is not more and 92 volumes ofphosphate bufferpH 2. 4 prepared by
than 2.0 per cent. dissolving 27.2 g of monobasic potassium phosphate
in 1000 ml of water, adjust the pH to 2.4 with
Inject the test solution and the reference solution.
orthophosphoric acid,
Calculate the content of CJsH2oFN304. - flow rate. 2 ml per minute,
spectrophotometer set at 294 nm,
Storage. Store protected from light.
- injection volume. 10 !Jl.
Inject reference solution (a). The test is not valid unless the
column efficiency in not less than 1400 theoretical plates.
Ofloxacin Tablets Inject the test solution and reference solution (b). Run the
chromatogram three times of the principal peak. In the
Ofloxacin Tablets contain not less than 90.0 per cent and not
chromatogram obtained with the test solution, the area of any
more than 110.0 per cent of the stated amount ofofloxacin,
secondary peak is not more than the area of the peak in the
CJSH20FN304' chromatogram obtained with reference solution (b) (1.0 per
Usual strengths. 200 mg; 400 mg. cent) and the sum of areas of all the secondary peaks is not
more than twice the area of the peak in the chromatogram
Identification obtained with the reference solution (b) (2.0 per cent).

In the Assay, the principal peak in the chromatogram obtained Other tests. Comply with the tests stated under the Tablets.
with the test solution corresponds to the peak in the Assay. Determine by liquid chromatography (2.4.14).
chromatogram obtained with the reference solution.
Test solution. Weigh and powder 20 tablets. Weigh accurately
Tests a quantity ofpowdered tablet containing 25 mg ofOfloxacin,
disperse in 60 m1 of methanol and dilute to 100 ml with methanol
Dissolution (2.5.2). and filter.
Apparatus No.1, Reference solution. A 0.025 per cent w/v solution of ojloxacin
Medium. 900 ml of 0.1 M hydrochloride acid, RS in methanol.
Speed and time. 50 rpm and 30 minutes.
Chromatographic system
Withdraw a suitable volume ofthe medium and filter. Measure - a stainless steel column 15 cm x 4.6 mm packed with
the absorbance ofthe filtrate, suitably diluted with the medium octadecylsilane bonded to porous silica (5 !Jm),
ifnecessary, at the maximum at about 294 nm (2.4.7). Calculate - mobile phase: a mixture of92 volumes ofbuffer solution
the content ofCJsH2oFN304 in the medium from the absorbance prepared by dissolving 27.2 g ofpotassium dihydrogen

1810
IP 2010 OLANZAPINE

phosphate in 1000 ml of water and adjust the pH to 2.4 Reference solution (aj. A 0.2 per cent w/v solution of
with orthophosphoric acid and 8 volumes of olanzapine RS in solvent mixture.
acetonitrile, Reference solution (bj. Dilute 1 ml ofreference solution (a) to
- flow rate. 2 ml per minute,
100 ml with solvent mixture.
- spectrophotometer set at 294 nm,
- injection volume. 10 Ill. Chromatographic system

Inject the reference solution. The test is not valid unless the - a stainless steel column 25 cm x 4.6 mm packed with
relative standard deviation for replicate injections is not more octadecylsilane bonded to porous silica (5 Ilm),
than 2.0 per cent. column temperature. 40°,
mobile phase: A. a mixture of 80 volumes of buffer
Inject the test solution and the reference solution. solution pH 6.8 prepared by dissolving 4.825 g of
Calculate the content ofClsHzoFN304. sodium dihydrogen orthophosphate monohydrate in
1000 ml of water, adjust pH to 6.8 with 10 per cent w/v of
Storage. Store protected from light and moisture.
sodium hydroxide and 20 volumes of acetonitrile,
B. acetonitrile,
flow rate. 1.2 ml per minute,
Olanzapine spectrophotometer set at 230 nm,
injection volume. 10 Ill.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
o 100 o
20 63 37
30 45 55
32 100 o
38 100 o
Inject reference solution (b). The test is not valid unless the
tailing factor is not more than 2.0 and the column efficiency in
Mol. Wt. 312.4
not less than 2000 theoretical plates.
Olanzapine is 2-methyl-4-(4-methyl-l-piperazinyl)-10H-
Inject the test solution and reference solution (b). In the
thieno[2,3-b][l ,5]benzodiazepine.
chromatogram obtained with the test solution, the area ofany
Olanzapine contains not less than 98.0 per cent and not more secondary peak is not more than 0.5 times the area ofthe peak
than 102.0 per cent ofC 17H zoN 4S, calculated on the anhydrous in the chromatogram obtained with reference solution (b) (0.5
basis. per cent) and the sum of areas of all the secondary peaks is
Category. Antipsychotic. not more than twice the area of the peak in the chromatogram
obtained with the reference solution (b) (2.0 per cent).
Dose. 10 mg daily.
Heavy metals (2.3.13). 1.0 g complies with the limit test for
Description. A yellow crystalline powder.
heavy metals, Method B (20 ppm).
Identification Sulphated ash (2.3.18). Not more than 0.1 per cent.
Determine by infrared absorption spectrophotometry (2.4.6). Water (2.3.43). Not more than 1.0 per cent, determined on
Compare the spectrum with that obtained with olanzapine RS LOg.
or with the reference spectrum of olanzapine.
Assay. Weigh accurately about 0.2 g, dissolve in 40 ml of
Tests glacial acetic acid. Titrate with 0.1 M perchloric acid,
Related substances. Determine by liquid chromatography determining the end-point potentiometrically (2.4.25). Carry
(2.4.14). out a blank titration.

Solvent mixture. 40 volumes of water and 60 volumes of 1 ml of 0.1 M perchloric acid is equivalent to 0.01562 g of
acetonitrile. C 17HzoN 4S.
Test solution. Dissolve 50 mg of the substance under Storage. Store protected from light and moisture, at a
examination in 25 ml ofsolvent mixture. temperature not exceeding 30°.

1811
OLANZAPINE TABLETS IP 2010

Olanzapine Tablets orthophosphate in 900 ml water, add 2 ml of


triethylamine and dilute to 1000 ml with wate/: Adjust
Olanzapine Tablets contain not less than 90.0 per cent and not the pH to 2.5 with orthophosphoric acid and 30 volumes
more than 110.0 per cent ofthe stated amount of olanzapine, of methanol,
C 17HzoN 4S. - flow rate. 1 ml per minute,
Usual strengths. 2.5 rng; 5 mg; 7.5 mg; 10 mg. - spectrophotometer set at 220 urn,
- injection volume. 10 Ill.
Identification Inject the reference solution. The test is not valid unless the
In the Assay, the principal peak in the chromatogram obtained tailing factor is not more than 2.0, the column efficiency is not
with the test solution corresponds to the peak in the less than 2500 theoretical plates. The relative standard
chromatogram obtained with the reference solution. deviation for replicate injections is not more than 2 per cent.
Inject the test solution and the reference solution.
Tests
Calculate the content ofC 17H zoN 4S.
Dissolution (2.5.2).
Apparatus No.1, Storage. Store protected from light and moisture, at a
temperature not exceeding 25°.
Medium. 900 ml of O. 01 M hydrochloric acid,
Speed and time. 50 rpm for 45 minutes.
Withdraw a suitable volume ofthe medium and filter. Determine
by liquid chromatography (2.4.14). Oleic Acid
NOTE - Protect all the solutions ji-om light.
H3C(H2C)6V=V(CH2)6COOH
Test solution. Use the filtrate, if necessary dilute with
dissolution medium. Mol. Wt. 282.5
Reference solution. Weigh 16 mg of olanzapine RS, dissolve Oleic Acid consists mainly of (Z)-octadec-9-enoic acid,
in about 2.5 ml of acetonitrile and dilute to 25 ml with 0.01 M ClsH340Z, together with varying amounts of saturated and
hydrochloroc acid.Dilute suitabely to get 0.00016 per cent other unsaturated fatty acids and is obtained by the hydrolysis
w/v in dissolution medium. of fats or fixed oils and separation of the liquid acids by
Chromatographic system as described under Assay, using expression or other suitable means. It may contain a suitable
Injection volume 50 ).1.1. antioxidant.
Inject the reference solution. The test is not valid unless the Category. Pharmaceutical aid (emulsion adjuvant).
tailing factor is not more than 2.0. The column efficiency is not Description. A clear, yellowish to pale brown, oily liquid; odour,
less than 2500 theoretical plates. characteristic. On exposure to air it darkens in colour and the
Inject the test solution and the reference solution. odour becomes more pronounced.
Calculate the content ofC 17H zoN 4S. Identification
D. Not less than 70 per cent ofthe stated amount ofC 17H zoN 4S. A. To 1 ml add 1 ml of ethanol (95 per cent,),' the solution is
Other tests. Comply with the tests stated under Tablets. clear. It turns orange or red on addition of 0.1 ml of methyl
Assay. Determine by liquid chromatography (2.4.14). orange solution.
Test solution. Take 10 intact tablets to a suitable volumetric B.Take a mixture of 1 ml of nitric acid and 1 ml of water in a
flask, disperse in acetonitrile and dilute with 0.01 M test-tube with an internal diameter of about 12.5 mm and add
hydrochloric acid to get a final concentration of 0.01 per cent 1 ml ofthe substance under examination on the surface of the
w/v ofOlanzapine. mixture. Introduce 0.5 g of copper turnings into the lower
layer and allow to stand under a hood for 4 hours; the upper
Reference solution. Weigh 10 mg of olanzapine RS, dissolve
layer solidifies.
in about 25 rnl of acetonitrile and dilute to 100 ml with 0.01 M
hydrochloric acid. C.Complies with the test for Iodine value (2.3.28).
Chromatographic system Tests
- a stainless steel column 25 em x 4.6 mm packed with
Weight per ml (2.4.29).0.889 g to 0.895 g.
octadecylsilane bonded to porous silica (5 Ilm),
- mobile phase: a mixture of70 volumes of buffersolution Peroxide value (2.3.35). Not more than 10.0.
prepared by dissolving 3 g of ammonium dihydrogen Acid value (2.3.23). 195 to 202, determined on 0.5 g..

1812
IP 2010 OMEPRAZOLE

Iodine value (2.3.28). 85 to 95, determined by MethodA.. Identification


Water-solubie acids. Shake 5 ml with 5 ml of water for Test A may be omitted if tests Band C are carried out. Tests B
2 minutes, allow the liquids to separate and filter the aqueous and C may be omitted if test A is carried out.
layer through paper moistened with water. To the filtrate add
A. Determine by infrared absorption spectrophotometry (2.4.6).
0.05 ml ofmethyl orange solution; the liquid does not become
Compare the spectrum with that obtained with omeprazole
red.
RS or with the reference spectrum of omeprazole.
Neutral fats and mineral oils. Boil I ml with 5 ml of 0.5 M
B. When examined in the range 230 nm to 360 nm (204.7), a
sodium carbonate and 25 ml of water in a large flask. The
0.002 per cent w/v solution in 0.1 M sodium hydroxide shows
solution, while still hot, is not more opalescent than
absorption maxima at about 276 nm and 305 nm; the ratio of
opalescence standard OS2 (204.1).
the absorbance at about 305 nm to that at about 276 nm, 1.6
Congealing point. Dry about 10 ml by heating to 110° with to 1.8.
frequent stirring, transfer to a test-tube about 20 rom in diameter, C. In the test for Related substances, the principal spot in the
cool and when at 15° immerse the tube in a suitable water-bath chromatogram obtained with the test solution corresponds to
so that the cooling takes place at the rate of2° per minute. Stir that in the chromatogram obtained with reference solution (a).
the sample with a thermometer; it does not become cloudy
until the temperature has fallen to 10°. On further cooling it Tests
congeals to a white solid or semi-solid mass at about 4°.
Appearance of solution. A 2.0 per cent w/v solution in
Sulphated ash (2.3.18). Not more than 0.1 per cent. dichloromethane is clear (204.1). .
Storage. Store protected from light and moisture in a refrigerator Light absorption (204.7). Absorbances of a freshly prepared
esc to 15°). 2.0 per cent w/v solution in dichloromethane at 400 nm,
Labelling. The label states (1) where applicable, that it is used 500 nm and 600 nm are not more than 0.25, 0.10 and 0:10
for external use only; (2) the name and concentration of any respectively.
added antioxidant. Related substances. A. Detennine by thin-layer chromato-
graphy (204.17), coating the plate with silica gel OF254.
Mobile phase. Arnixture of50 volumes ofbenzene, 30 volumes
of ethyl acetate and 10 volumes of methanol.
Omeprazole Test solution. Dissolve 0.4 g of the substance under
examination in 100 ml ofethanol.

O~N:/'
H
I CH3
Reference solution (a). A 004 per cent w/v solution of

~
:;/ II N omeprazole RS in ethanol.
rr,)-8
HCO~N
OCH Reference solution (b). A 0.004 per cent w/v solution of
3
3 CH 3 omeprazole RS in ethanol.
Reference solution (c). A 0.002 per cent w/v solution of
omeprazole RS in ethanol.
C17H19N303S Mol. Wt. 34504
Apply to the plate 10 III of each solution. After development,
Omeprazole is 5-methoxy-2-[[(4-methoxy-3,5-
dry the plate in air and examine in ultraviolet light at 254 nm
dimethylpyridin-2-yl)methyl]sulfinyl]-IH-benzirnidazole.
immediately. Any secondary spot in the chromatogram
Omeprazole contains not less than 99.0 per cent and not mbre obtained with the test solution is not more intense than the
than 101.0 per cent of C17HI9N303S, calculated on the dried spot in the chromatogram obtained with reference solution (c)
basis. and the total intensity of all such spots in the chromatogram
NOTE - Peiform the· tests and assay in subdued light and obtained with the test solution is not more than the intensity
use low-actinic glassware. of the spot obtained with reference solution (b).
B. In the Assay, the sum of the areas of all the secondary
Category. Antiulcerative (proton pump inhibitor).
peaks is not greater than 1.5 rer cent of the total area of all
Dose. For duodenal and gastric ulcers and for reflux peaks.
oesophagitis, 20 to 40 mg daily; for Zollinger-Ellison syndrome,
Heavy metals (2.3.13). The residue obtained in the test for
initially 60 mg once daily; usual range, 20 to 120 mg daily.
Sulphated ash, complies with the limit test fo~ heavy metals,
Description. A white or almost white powder. Method B (20 ppm).

1813
OMEPRAZOLE IP 2010

Sulphated ash (2.3.18). Not more than 0.2 per cent. filter. Dilute 2 ml of the filtrate to 1QO mI with O.lM sodium
hydroxide.
Loss on drying (2.4.19). Not more than 0.2 per cent, determined
on 1.0 g by drying in an oven at 60° at a pressure not exceeding When exarninedin the.range 230 nm to 360 nm (2.4.7); the
0.7 kPa for 4 hours. resulting solution shows absorption maxima at about 276 nm
and305nm.
Assay. Determine by liquid chromatography (2.4.14).
B. In the Assay, the principal peak in the chromatogram
Test solution. A 0.005 per cent w/v solution of the substance
obtained with the test solution corresponds to the peak due
under examination in the mobile phase.
to omeprazole in the chromatogram obtained with the reference
Reference solution. A 0.005 per cent w/v solution of solution.
omeprazole RS in the mobile phase.
Chromatographic system Tests
- a stainless steel column 30 cm x 3.9 mm, packed with Dissolution (2.5.2).
octadecylsilane bonded to porous silica (5 ILm),
- mobile phase: a mixture of 65 volumes of phosphate A. Apparatus No.1,
buffer pH 7.4 and 35 volumes of acetonitrile, Medium. 900 ml of 0.1 M hydrochloric acid, .
- flow rate. 1 ml per minute, Speed and time. 100 rpm and 2 hours.
- spectrophotometer set at 302 nm, Tap the granules from a capsule slightly with a glass rod to
- injection volume. 20 ILL make them settle to the bottom. Rotate the paddle at 100 rpm
Inject the reference solution. Repeat the procedure at least for 2 hours, drain the solution slowly without losing any
five times and measure the peak responses ofthe peak due to granules. Transfer them quantitatively to a 1OO-ml volumetric
omeprazole. The relative standard deviation of the replicate flask, add 20 ml of 0.1 M sodium hydroxide and mix with the
injections is not more than 2.0 per cent. aid of ultrasound. Dilute to volume with 0.1 M sodium
hydroxide, centrifuge about 15 ml for 5 minutes and dilute
Inject the test solution and the reference solution. 5.0 mI ofthe clear supernatant liquid to 50.0 ml with the mobile
Calculate the content ofC17HJ9N303S, phase. Using the resulting solution as the test solution, carry
out the determination as described in the Assay. Calculate the
Storage. Store protected from light and moisture in a refrigerator
content of C17H19N303S in the supernatant liquid. Calculate
(2° to 8°).
the percentage of omeprazole released in the acid medium by
NOTE - A combination of elevated temperatures (3JO-500) subtracting the content of C17H19N303S in the test solution
and high humidity degrades Omeprdzole. It rapidly degrades from the total content ofomeprazole determined in the Assay.
under acidic conditions.
Not more than 15 per cent ofthe stated amount ofC 17HJ9N303S
is dissolved in 2 hours.

Omeprazole Capsules B. Apparatus No.1,


Medium. 900 ml ofphosphate bufferpH 6.8,
Omeprazole Capsules contain enteric-coated granules of Speed and time. 100 rpm and 45 minutes.
Omeprazole.
Tap the granules from a capsule slightly with a glass rod to
Omeprazole Capsules contain not less than 90.0 per cent and make them settle to the bottom. Rotate the paddle at 100 rpm
not more than 110.0 per cent of the stated amount of for 45 minutes and filter the solution. Using the filtered medium
omeprazole, C17HI9N303S, as the test solution, carry out the determination as described
NOTE - Perform the tests and assay in subdued light and in the Assay. Calculate the content of C17H19N303S in the
use low-actinic glassware. medium.

Usual strength. 20 mg. D. Not less than 70 per cent of the stated amount of
C17HI9N303S,
Identification
Other tests. Comply with the tests stated under Capsules.
A.To a quantity of the contents of the capsules containing
Loss on drying (2.4.19). Not more than 3.0 per cent, determined
50 mg of Omeprazole in a 1OO-ml volumetric flask add about
on 0.5 g of the contents of the capsules by drying in an oven
70 m1 of O. I M sodium hydrOXide. Mixin an ultrasonic bath for
at 60° at a pressure not exceeding 0.7 kPa for 4 hours.
about 5 minutes and heat on a water-bath for 10 minutes.
Cool, make up to volume with 0.1 M sodium hydroxide and Assay. Determine by liquid chromatography (2.4.14).

1814
IP 2010 ONDANSETRON HYDROCHLORIDE

Test solution. Mix the contents of 20 capsules. Weigh and ondansetron hydrochloride RS or with the reference spectrum
transfer the granules containing·about 20 mg of Omeprazole of ondansetron hydrochloride.
to a 100-ml volumetric flask, add 20 ml of 0.1 M sodium
B. It gives the reactions ofchlorides"(2.3.12).
hydroxide, mix with the aid ofultrasound and dilute to volume
with 0.1 M sodium hydroxide. Centrifuge for 5 minutes and
Tests
dilute 5.0 ml ofthe clear supernatant liquid to 50.0 ml with the
mobile phase. Related substances. Determine by liquid chromatography
Reference solution. Take 20 mg of omeprazole RS in a dry, (2.4.14).
stoppered test-tube, add 20.0 rnl of 0.1 M sodium hydroxide, Use the chromatographic system,the test solution and
shake vigorously for 5 minutes and dilute 1.0 ml ofthe solution reference solution (b) described under Assay.
with the mobile phase to produce 50.0 ml.
Inject the test solution and reference solution (b). In the
Chromatographic system chromatogram obtained with the test solution, the area of any
- a stainless steel column 30 cm x 3.9 mm, packed with secondary peak is not more than 0.2 times the area ofthe peak
octadecylsilane bonded to porous silica (5 11m), in the chromatogram obtained with reference solution (b)
- mobile phase: a mixture of 65 volumes of phosphate (0.2 per cent) and the sum of the areas of all the secondary
buffer pH 7.4 and 35 volumes of acetonitrile, peaks is not more than 0.5 times the area of the peak in the
- flow rate. 1 ml per minute, chromatogram obtained with reference solution (b) (0.5 per
- spectrophotometer set at 302 nm, cent).
- injection volume. 20 Ill.
Sulphated ash (2.3.18). Not more than 0.1 percent.
Inject the reference solution. Repeat the procedure at least
five times and measure the peak responses of the peak due to Water (2.3.43).9.0 to 10.5 per cent, determined on 0.2 g.
omeprazole. The relative standard deviation of the replicate Assay. Determine by liquid chromatography (2.4.14).
injections is not more than 2.0 per cent.
Test solution. Dissolve 50 mg of the substance under
Calculate the content ofCi7H 19N 30 3S in the capsules. examination in 50 ml of the mobile phase and filter. Dilute
Storage. Store protected from light and moisture. 5.0 ml ofthe solution to 50.0 ml with the mobile phase.
Reference solution (a). A 0.01 per cent w/v solution of
ondansetron hydrochloride RS in the mobile phase.
Ondansetron Hydrochloride Reference solution (b). Dilute 1 ml ofreference solution (a) to
100.0 ml with the mobile phase.
Reference solution (c). A solution containing 0.01 per cent
w/v of ondansetron hydrochloride RS and 0.002 per cent w/v
of 3[Dimethylaminomethylj-1, 2, 3, 9-tetrahydro-9-methyl-
4H-carbozol-4-one RS (ondansetron impurity A RS) "in the
mobile phase.
Chromatographic system
ClsH19N30,HCl,2HzO Mol. Wt. 365.9 - a stainless steel column 25 cm x 4.6 mm, packed with
Ondansetron HydrocWoride is (RS)-9-methyl-3-[(2-methyl-lH- porous silica (5 11m) with chemically bonded nitrile
imidazol-l-yl)methyl]-1 ,2,3,9-tetrahydro-4H-carbazol-4-one groups (Such as Supelco LC-CN),
hydrochloride dihydrate. - mobile phase: a mixture of 50 volumes of 0.02 M
monobasic potassium phosphate with the pH
Ondansetron Hydrochloride contains not less than 98.0 per
previously adjusted to 5.4 with 1 M sodium hydroxide
cent and not more than 102.0 per cent of ClsH19N30,HCl,
and 50 volumes of acetonitrile,
calculated on the anhydrous basis.
- flow rate. 1.5 ml per minute,
Category. Antiemetic. (5-HT3 receptor antagonist) - spectrophotometer set at 216 nm,
Description. A white or almost white powder. - injection volume. 10 Ill.

Identification Inject reference solution (c). The test is not valid unless the
relative retention time for ondansetron is about 1.0 and for
A. Determine by infrared absorption spectrophotometry ondimsetron impurity A is about 1.1. The resolution between
(2.4.6).Compare the spectrum with that obtained with ondansetron and ondansetron impurity A is not less than 1.5.

1815
ONDANSETRON INJECTION IP 2010

Inject reference solution (a). The tailing factor is not more Reference solution (b). Dilute 1 ml ofreference solution (a) to
than 2.0 and the relative standard deviation for replicate 100 ml with the mobile phase.
injections is not more than 2.0 per cent. Reference solution (c). A solution containing 0.01 per cent
Inject the test solution and reference solution (a). w/v of ondansetron hydrochloride RS and 0.005 per cent w/v
of 3[Dimethylaminomethyl}-1, 2, 3, 9-tetrahydro-9-methyl-
Calculate the content ofClsHI9N30,HCI.
4H-carbozol-4-one RS (ondansetron impurity A RS) in the
Storage. Store protected from light and moisture, at a mobile phase.
temperature not exceeding 30°.
Chromatographic system
- a stainless steel column 20 cm x 4.6 lTIlll, packed with
porous silica (5 11m) bonded to nitrile groups (such as
Ondansetron Injection Supelco LC-CN),
- mobile phase: a mixture of 50 volumes of 0.02 M
Ondansetron Hydrochloride Injection monobasic potassium phosphate with the pH
previously adjusted to 5.4 with 1 M sodium hydroxide
Ondansetron Injection contains not less than 95.0 per cent
and 50 volumes of acetonitrile,
and not more than 105.0 per cent of the stated amount of
- flow rate. 1.5 rn1 per minute,
ondansetron, ClsH19N30.
- spectrophotometer set at 216 nm,
Usual strengths. 2 mg; 4 mg; 8 mg. - injection volume. 10 Ill.
Inject reference solution (c). The test is not valid unless the
Identification
relative retention time for ondansetron is about 1.0 and for
In the Assay, the principal peak in the chromatogram obtained ondansetron impurity A is about 1..1. The resolution between
with the test solution corresponds to the peak in the ondansetron and ondansetron impurity A is not less than 1.5.
chromatogram obtained with the reference solution (a). Inject reference solution (a). The tailing factor is not more
than 2.0 and the relative standard deviation for replicate
Tests injections is not more than 2.0 per cent.
pH (2.4.24).3.3 to 4.0. Inject the test solution and reference solution (a).
Related substances. Determine by liquid chromatography Calculate the content ofCIsHI9N30 in the injection.
(2.4.14). Storage. Store protected from light, at a temperature not
Use the chromatographic system, test solution and reference exceeding 30°.
solution (b) described under Assay. Labelling. The label states the strength in terms of the
Inject the test solution and reference solution (b). In the equivalent amount of ondansetron.
chromatogram obtained with the test solution, the area of any
secondary peale is not more than 0.2 times the area ofthe peak
in the chromatogram obtained with reference solution (b) (0.2
per cent) and the sum ofthe areas of all the secondary peaks
Ondansetron Orally Disintegrating
is not more than 1.5 times the area of the peak in the Tablets
chromatogram obtained with reference solution (b) (1.5 per
Ondansetron Orally Disintegrating Tablets contain not less
cent).
than 90.0 per cent and not more than 110.0 per cent of the
Bacterial endotoxins (2.2.3). Not more than 9.9 Endotoxin stated amount of ondansetron, ClsH19N30.
Units per mg of ondansetron.
Usual strength. 4 mg; 8 mg.
Other tests. Complies with the tests stated under Parenteral
Preparations (Injections). Identification
Assay. Determine by liquid chromatography (2.4.14).• In the Assay, the principal peak in the chromatogram obtained
with the test solution corresponds to the peak in the
Test solution.Transfer an accurately measured volume of the chromatogram obtained with the reference solution.
injection containing about 2 mg of ondansetron to a 25-ml
volumetric flask, dilute to volume with the mobile phase and mix. Tests
Reference solution (a). A 0.01 per cent w/v solution of Dissolution (2.5.2).
ondansetron hydrochloride RS in the mobile phase. Apparatus No.1,

1816
IP 2010 ONDANSETRON ORALLY DISINTEGRATINGTABLETS

Medium. 500 ml of 0.1 M hydrochloric acid, Inject reference solution (d) and the test solution. In the
Speed and time. 50 rpm and 10 minutes. chromatogram obtained with the test solution, the area of the
peak due to 2-methylimidazole is not more than 0.1 5 per cent,
Withdraw a suitable volume ofthe medium and filter. Measure
multiply with response factor 0.5, the area of peak due to
the absorbance of the filtrate, suitably diluted with the
ondansetron impurity D is not more than 0.12 per cent, multiply
dissolution medium ifnecessary, at the maximum at about 31 0
with response factor 1.2. The area of any other secondary
nm (2.4.7). Calculate the content ofClsH19N30 in the medium
peak is not more than 0.1 per cent and the sum of all the
from the absorbance obtained by using a solution of known
secondary peaks is not more than 0.5 per cent.
concentration of ondansetron RS in same medium.
Water (2.3.43). Not more than 4.0 per cent, determined on
D. Not less than 80 per cent ofthe stated amount ofC ls H19N30.
LOg.
Related substances. Determine by liquid chromatography
(2.4.14). Other tests. Comply with the tests stated under tablets.

Test solution. Disperse a quantity of powdered tablets Assay. Determine by liquid chromatography (2.4.14).
containing about 40 mg of ondansetron with 100.0 ml of the Test solution. Weigh and powder 20 tablets. Disperse a quantity
mobile phase. Centrifuge a portion ofthis solution at 3000 rpm of powder containing about 40 mg of ondansetron with
for 10 minutes. Use the supernatant. 100.0 mlO.01 Mhydrochloricacid.Dilute 1.0 ml ofthe solution
Reference solution (a). A 0.004 per cent w/v solution of to 10.0 ml with 0.01 Mhydrochloric acid.
1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one Reference solution (a). A 0.004 per cent w/v solution of
RS (ondansetron impuirty DRS) in acetonitrile. ondansetron RS in 0.01 M hydrochloric acid.
Reference solution (b). A 0.004 per cent w/v solution of Reference solution (b). A 0.014 per cent w/v solution of
2-methylimidazole in acetonitrile. 3[Dimethylamino methylj-1,2,3,9-tetrahydro-9-methyl-H-
Reference solution (c). A 0.004 per cent w/v solution of carbozol-4-one-RS (ondansetron impurity A RS) in 0.01 M
ondansetron RS in acetonitriile. hydrochloric acid.
Reference solution (d). Dilute 5.0 ml ofreference solution (c) Reference solution (c). Transfer 8.0 ml each of reference
to 100.0 ml with the mobile phase. solution (a) and (b) to 50-ml volumetric flask and dilute to
Reference solution (e). Dilute 10.0 ml ofreference solution (c) volume with 0.01 M hydrochloric acid.
to 100.0 ml with the mobile phase. Chromatographic system
Reference solution (j). Transfer 5.0 ml of each reference - a stainless steel column 25 cm x 4.6 rom, packed with
solution (a), (b) and (c) to a 100-ml volumetric flask, dilute to porOl.jS silica bonded to nitrile groups (5 /-lm),
volume with the mobile phase. - mobile phase: a mixture of52 volumes of0.272 per cent
w/v solution of monobasic potassium phosphate,
Chromatographic system
adjusted to pH 5.4 with 1 M sodium hydroxide and 48
- a stainless steel column 25 cm x 4.6 rom, packed with
volumes of acetonitrile,
porous silica chemically bonded to nitrile groups (5 /-lm),
- flow rate. 1.5 ml per minute,
- mobile phase: a mixture of 80 volumes of phosphate
- spectrophotometer set at 216 urn,
buffer prepared by dissolving 2.72 g of monobasic
- injection volume. 10 /-ll.
potassium phosphate in 1000 ml of water, adjusted to
pH 5.4 with 1 M sodium hydroxide and 20 volumes of Inject reference solution (c). The test is not valid unless the
acetonitrile, resolution between the peaks due to ondansetron and
- flow rate. 1.5 ml per minute, ondansetron impurity A is not less than 1.5. The relative
- spectrophotometer set at 216 nm, retention time with reference to ondansetron for ondansetron
- injection volume. 20 /-ll. impurity A is about 1.1. The tailing factoris not more than 2.0
for ondansetron peak.
Inject reference solution (t). The test is not valid unless the
resolution between ondansetron and adjacent peak is not less Inject reference solution (a) and the test solution.
than 1.5, the theoretical plates is not less than 8000 for
Calculate the content ofCIsH19N30 in the tablets.
ondansetron and tailing factor is not more than 2.0.
Storage. Store protected form light and moisture, at a
Inject reference solution (e). The signal to noise ratio for the
temperature not exceeding 30°.
ondansetron peak is not less than 15. The relative retention
time with reference to ondansetron for 2-methylimidazole is Labelling. The label states the active ingredient in terms of
about 0.16 and for ondansetron impurity D is about 0.45. equivalent amount of ondansetron.

1817
ONDANSETRON ORAL SOLUTION IP 2010

Ondansetron Oral Solution Chromatographic system


- a stainless steel column 25 cm x 4.6 mm, packed with
Ondansetron Hydrochloride Oral Solution porous silica bonded to nitrile groups (5 /J.m),
- mobile phase: a mixture of 80 volumes of 0.02 M
Ondansetron Oral Solution is a solution of Ondansetron
monobasic potassium phosphate, previously adjusted
Hydrochloride in a suitable vehicle..
to pH 5.4 and 20 volumes of acetonitrile,
Ondansetron Oral Solution contains not less than 95.0 per - flow rate. 1.5ml per minute,
cent and not more than 105.0 per cent ofthe stated amount of - spectrophotometer set at 328 nm,
ondansetron, ClsH'9N30. injection volume. 20/J.1.
Usual strength. 2 mg per 5 ml; 4 mg per 5 ml. Inject reference solution (b). The test is not valid unless the
resolution between ondansetron impurity D and ondansetron
Identification impUlity C is not less than 2.0, the tailing factor for ondansetron
impurity D is not more than 2.0 and the relative standard
A. Detennine by thin-layer chromatography (2.4.17), coating deviation forreplicate injections is notmore than 4.0 per cent.
the plate with silica gel G.
Inject reference solution (a) and the test solution.
Mobile phase. A mixture of 90 volumes of chloroform, 50 Calculate the content of ondansetron impurity D in the oral
volumes of ethyl acetate, 40 volumes of methanol and 1volume solution.
of ammonium hydroxide.
Related substances. Detennine by liquid chromatography
Test solution. Dilute an accurately measured volume of the (2.4.14), as described under Assay with the following
oral solution containing about 20 mg of ondansetron to 100.0 modifications.
ml in a mixture of 50 volumes of methanol and 50 volumes of
Test solution. Weigh accurately a quantity of oral solution
water.
containing about 45 mg of Ondansetron Hydrochloride in
Reference solution. A 0.025 per cent w/v solution of 50-ml volumetric flask, dissolve and dilute with the mobile
ondansetron RS in methanol. phase and mix. Dilute 5.0 ml ofthis solution to 50 ml with the
mobile phase.
Apply 10 /J.I of each solution. Allow the solvent front to rise
15 cm. Dry the plate in air and examine in ultraviolet light at Inject reference solution (c). The test is not valid unless the
254 nm. The chro\natogram obtained with the test solution resolution between ondansetron impuirty A and ondansetron
corresponds to that obtained with the reference solution. is not less than 1.5, the tailing factor is not less than 2.0 and
the relative standard deviation for replicate injections is not
B. In the Assay, the principal peak in the chromatogram more than 1.5 per cent. The relative retention time with
obtained with the test solution corresponds to the peak in the reference to ondansetron for ondansetron impurity A is
chromatogram obtained with the reference solution. about 1.1.
Inject reference solution (b) and the test solution. In the
Tests chromatogram obtained with the test solution, the area ofthe
peak due to ondansetron impurity D is not more than
pH (2.4.24).3.3 to 4.0.
0.1 per cent, the area of each peak due to imidazole, 2-methyl
Ondansetron impurity D. Not more than 0.1 per cent. imidazole, des-(-methy1)ondansetron hydrochloride,
Detennine by liquid chromatography (2.4.14). N-Desmethyl ondansetron maleate, ondansetron impurity A
is not more than 0.2 per cent. The area of any other secondary
Test solution. Dilute an accurately measured volume of oral peak is not more than 0.2 per cent and the sum of all the
solution to obtain a solution having a concentration of 0.08 secondary peaks is not more than 0.5 per cent.
per cent w/v of ondansetron in the mobile phase. Other tests. Complies with the tests stated under Oral Liquids.
Reference solution (a). A 0.00005 per cent w/v solution of Assay. Detennine by liquid chromatography (2.4.14).
1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol~4-on
e
RS (ondansetron impurity D RS) in the mobile phase. Test solution. Dilute a volume of the oral solution containing
about 9 mg ofondansetron to 100.0 ml with themobi1e phase.
Reference solution (b). A solution containing 0.00005 per cent
w/v of ondansetron impurity D RS and 0.0002 per cent w/v of Reference solution (a). A 0.01 per cent w/v solution of
N-methyl [2 -(2 -methylbenzhydryloxy) ethyl} am ine ondansetron hydrochloride RS in the mobile phase.
hydrochloride RS (ondansetron impurity C RS) in the mobile Reference solution (b). Dilute 1 ml ofreference solution (a) to
phase. 100.0 ml with the mobile phase.

1818
IP 2010 ONDANSETRON TABLETS

Reference solution (c). A solution containing 0.01 per cent Medium. 500 ml ofwatel;
w/v of ondansetron hydrochloride RS and 0.002 per cent w/v Speed and time. 50 rpm and 45 minutes.
of 3[DimethylaminomethylJ-l, 2, 3, 9-tetrahydro-9-methyl-
Withdraw a suitable volume ofthe medium and filter. Measure
4H-carbozol-4-one RS (ondansetron impurity A RS) in the
the absorbance of the filtered solution, suitably diluted with
mobile phase.
the medium if necessary, at the maximum at about 310 nm
Chromatographic system (2.4.7). Calculate the content ofCIsHI9N30 in the medium from
- a stainless steel column 25 cm x 4.6 mrn, packed with the absorbance obtained from a solution of known
porous silica (5 11m) with chemically bonded nitrile concentration of ondansetron hydrochloride dihydrate RS
groups (such as Supelco LC-CN), in the same medium.
- mobile phase: a mixture of 50 volumes of 0.02 M
1 mg of CIsHI9N30 is equivalent to 1.25 mg of
monobasic potassium phosphate with the pH
C,sHI9N30,HCl,2HzO.
previously adjusted to 5.4 with 1 M sodium hydroxide
and 50 volumes of acetonitrile, D. Not less than 70 per cent ofthe stated amount ofClsHl9N30.
flow rate. 1.5 ml per minute, Related substances. Determine by liquid chromatography
- spectrophotometer set at 216 nm, (2.4.14).
- injection volume. 10 Ill. Use the chromatographic system, test solution and reference
Inject reference solution (c). The test is not valid unless the solution (b) described under Assay.
relative retention time for ondansetron is about 1.0 and for Inject the test solution and reference solution (b). In the
ondansetron impurity A is about 1.1. The resolution between chromatogram obtained with the test solution, the area ofany
ondansetron and ondansetron impurity A is not less than 1.5. secondary peak is not more than 0.2 times the area ofthe peak
Inject reference solution (a) The tailing factor is not more in the chromatogram obtained with reference solution (b) (0.2
than 2.0 and the relative standard deviation for replicate per cent) and the sum of the areas of all the secondary peaks
injections is not more than 2.0 per cent. is not more than 0.5 times the area of the peak in the
Inject tbe test solution and reference solution (a). chromatogram obtained with reference solution (b) (0.5 per
cent).
Calculate the content ofClsHl9N30, HCl in the oral solution.
Uniformity of content. Comply with the test stated under
Microbial contamination (2.2.9). Complies with the microbial Tablets.
contamination test. The total aerobic count is not more than
Determine by liquid chromatography (2.4.14), using the
100 cfu per g, Enterobacteriaceae count is not more than 10
chromatographic conditions and reference solution (a)
cfu per g and the total combined molds and yeasts count is
described in the Assay.
not more than 50 cfu per g.
Test solution. Disperse one tablet in' the mobile phase and
Storage. Store protected from light and moisture.
dilute to obtain a solution containing 0.01 per cent w/v of
Ondanseteron Hydrochloride and filter.
Calculate the content ofCIsHI9N30 in the tablet.
Ondansetron Tablets Other tests. Comply with the tests stated under Tablets.
Ondansetron Hydrochloride Tablets Assay. Determine by liquid chromatography (2.4.14).
Ondansetron Tablets contain not less than 95.0 per cent and Test solution. Weigh and powder 20 tablets. Weigh accurately
not more than 105.0 per cent of the stated amount of a quantity ofpowder containing about 50 mg of ondansetron,
ondansetron, ClsH19N30. disperse in 50 ml ofthe mobile phase and filter. Dilute 5.0 ml of
Usual strengths. 2 mg; 4 mg; 8 mg the solution to 50.0 ml with the mobile phase.
Reference solution (a). A 0.01 per cent w/v solution of
Identification ondansetron hydrochloride RS in the mobile phase.
In the Assay, the principal peak in the chromatogram obtained Reference solution (b). Dilute 1 ml ofreference solution (a) to
with the test solution corresponds to the peak in the 100 ml with the mobile phase.
. chromatogram obtained withthe reference solution (a). Reference solution (c). A solution containing 0.01 per cent
w/v of ondansetron hydrochloride RS and 0.002 per cent w/v
Tests
of 3[DimethylaminomethylJ-l, 2, 3, 9-tetrahydro-9-methyl-
Dissolution (2.5.2) 4H-carbozol-4-one RS (ondansetron impurity A RS) in the
Apparatus No.1, mobile phase.

1819
ORAL REHYDRATION SALTS IF 2010

Chromatographic system Composition ofthe formulation in terms ofthe amount, in g, to


- a stainless steel column 25 cm x 4.6 mm, packed with be dissolved in sufficient water to produce 1000 ml.
porous silica (5 /lm) bonded to nitrile groups (such as
Sodium Chloride 2.6
Supelco LC-CN),
Dextrose (anhydrous) 13.5
mobile phase: a mixture of 50 volumes of 0.02 M
or
monobasic potassium phosphate with the pH
Dextrose Monohydrate 14.85
previously adjusted to 5.4 with 1 M sodium hydroxide
and 50 volumes of acetonitrile, Potassium Chloride 1.5
flow rate. 1.5 ml per minute, Sodium Citrate 2.9
spectrophotometer set at 216 nm, The molar concentrations of sodium, potassium, chloride and
- injection volume. 10 Ill. citrate ions in terms ofmillimoles per litre are given below:
Inject reference solution (c). The test is not valid unless the mmol/l
relative retention time for ondansetron is about 1.0 and for Sodium 75
ondansetron impurity A is about 1.1. The resolution between Potassium 20
ondansetron and ondansetron impurity A is not less than 1.5.
Chloride 65
Inject reference solution (a). The tailing factor is not more Citrate 10
than 2.0 and the relative standard deviation for replicate
Dextrose 75
injections is not more than 2.0 per cent.
The total osmolar concentration of the solution in terms of
Inject the test solution and reference solution (a).
mOsmol per litre is 245.
Calculate the content ofC,sH,9N30 in the tablets.
Oral Rehydration Salts contain not less than 90.0 per cent and
Storage. Store protected from light and moisture, at a not more than 110.0 per cent ofthe stated amount ofDextrose
temperature not exceeding 30°. (anhydrous) or Dextrose Monohydrate (as appropriate) and
Labelling. The label states the strength in terms of the ofthe requisite amQunts ofsodium, Na, potassium, K, chloride,
equivalent amount of ondansetron. Cl, and citrate, C6H s0 7, calculated from the stated amounts of
the relevant constituents.
Description. A white to creamy-white, amorphous or
crystalline powder; odourless.
Oral Rehydration Salts
ORS Powder Identification
Oral Rehydration Salts are dry, homogeneously mixed powders A. When heated, melting and charring occurs and an odour of
containing Dextrose, Sodium Chloride, Potassium Chloride burnt sugar is produced.
and either Sodium Bicarbonate or Sodium Citrate for use in B. Add a few drops ofthe solution prepared as directed in the
oral rehydration therapy after being dissolved in the requisite label to 5 ml of potassium cupri-tartrate solution; a copious
amount ofwater. red precipitate is produced on boiling.
They may contain suitable flavouring agents and, where C. Gives reaction A of sodium salts, reaction A of potassium
necessary, suitable flow agents in the minimum quantity salts and reaction A of chlorides (2.3.1).
required to achieve a satisfactory product but may not contain
artificial sweetening agents like mono- and/or poly- D. A quantity containing about 50 mg of citric acid gives the
saccharides. If saccharin/saccharin sodium or aspartame is reactions ofcitrates (2.3.1).
used in preparations meant for paediatric use, the concentration
of saccharin should be such that its daily intake is not more
Tests
than 5 mg/kg ofbody weight and that of aspartame should be Uniformity of weight. Comply with the test for contents of
such that its daily intake is not more than 40 mg/kg of body packaged dosage forms (2.5.6).
weight.
Seal test (onlyfor sachets). Loosely bundle 10 sachets with a
Category: Replacement solution for diarrhoeal rehydration. rubber band and submerge the bundle under water in a vacuum
Usual strength. A formulation of reduced osmolarity (given desiccator maintained at a pressure not exceeding 18 kPa for
below) recommended by the World Health Organization one minute. Examine the bundle for any fine stream ofbubbles.
(WHO) for the Diarrhoeal Diseases Control Programme, and Re-establish normal pressure and open the bundle. No
ofthe United Nations Children's Emergency Fund (UNICEF). penetration of water is observed in any sachet.

1820
IP 2010 ORMELOXIFEN HYDROCHLORIDE

Other tests. Comply with the tests stated under Oral Powders. in g ofC6H 120 6and C6H1206,H20 respectively, as appropriate,
in the weight taken for the Assay.
Assay. Carry out the following assays on the well-mixed
contents of an individual sachet or on a suitable sample from Storage. Store protected from moisture in sachets, preferably
the well-mixed contents ofa bulle container. Where the amount made ofaluminum foil, containing sufficient powder for a single
in an individual sachet is insufficient to carry out all the assays, dose or for a day's treatment or for use in hospitals, in bulle
take a separate sachet for the Assay for citrate and for the containers containing sufficient quantity to produce a volume
Assay for dextrose. For the Assays for total sodium, for of solution appropriate to the daily requirements of the
potassium and for total ch.loride weigh accurately about hospital concerned.
8.0 g and dissolve in sufficient water to produce 500.0 ml
Labelling. The label states (l) for sachets, the total weights,
(solution A).
in g, of each constituent; (2) for bulle containers, the weights,
For total sodium - Dilute a suitable volume of solution A in g, of each constituent in a stated quantity, in g, of the oral
with a s1,1fficient volume of a solution of strontium chloride powder; (3) the molar concentration in millimoles per litre of
such thatthe final solution contains a 1500 to 2000-fold excess sodium, potassium, chloride and citrate ions, and of dextrose
of strontium ions and determine by Method A for atomic as well as the total osmolar concentration in mOsmol per litre
absorption spectrophotometry (2.4.2), measuring at 589 nm of the solution prepared from the oral powder; (4) the total
and using sodium solution AAS, suitably diluted with the weight ofthe contents of the container; (5) the directions for
strontium chloride solution, for the standard solutions or, use; (6) that any portion ofthe solution prepared from the oral
alternately by Method A for flame photometry (2.4.4). powder that remains unused for 24 hours after preparation
should be discarded; (7) the storage conditions. g, of the oral
1 g ofSodium Chloride, and ofSodium Citrate is equivalent to
powder.
0.3934 and 0.2345 g ofNa respectively.
For potassium - Dilute a suitable volume of solution A with
a sufficient volume of solution of strontium chloride such
that the final solution contains a 1500 to 2000-fold excess of Ormeloxifene Hydrochloride
strontium ions and determine by Method A for atomic
Centchroman Hydrochloride; Centchroman
absorption spectrophotometry (2.4.2), measuring at 767 nm
and using potassium solution AAS, suitably diluted with the
strontium chloride solution, for the standard solutions or,
H3 CO 0 ,CH 3
alternatively by Method A for flame photometry (2.4.4).
CH 3
1 g ofPotassium Chloride is equivalent to 0.5245 g ofK.
For total chloride - Titrate 50 ml of solution A with 0.1 M I I":

Y
~
silver nitrate using potassium chromate solution as indicator. • HCI
1 ml of 0.1 M silver nitrate is equivalent to 0.003545 g ofCI.
1 g of Sodium Chloride, and of Potassium Chloride is
equivalent to 0.6066 and 0.4756 g ofCl respectively. O~O
For citrate - Weigh accurately about 2.0 g and dissolve in
50 ml of anhydrous glacial acetic acid by heating at about
50°. Cool, allow to stand for 10 minutes. Titrate with 0.1 M Mol. Wt. 493.5
perchloric acid, using 1-naphtholbenzein solution as
Ormeloxifene Hydrochloride is trans-7-methoxy-2,2-
indicator. Carry OJ.lt a blank titration.
dimethyl-3-phenyl-4[4-(2-
1 ml of 0.1 M perchloric acid is equivalent to 0.006303 g of pyrrolidinoethoxy)phenyl]chroman hydrochloride.
CJfS07' Ormeloxifene Hydrochloride contains not less than 98.5 per
1 g ofSodium Citrate is equivalentto 0.6430 g ofC6Hs0 7• cent and not more than 101.5 per cent of C30H3sN03,HCl,
For dextrose - Weigh accurately about 7.5 g, dissolve in calculated on the dried basis.
40 ml of water, add 0.5 ml of dilute ammonia solution, and Category. Antifertility agent (female oral contraceptive).
dilute to 50 ml with water. Mix well, allow to stand for
Dose. 120 mg twice a week, 3 days apart, for three months and
30 minutes, filter the solution, ifturbid, and measure the optical
thereafter once a week.
rotation in a 2-dm tube (2.4.22). The observed rotation, in
degrees, multiplied by 0.9477 and 1.0424 represents the weight Description. A white to off-white powder.

1821
ORMELOXIFEN HYDROCHLORIDE IP 2010

Identification . Chromatographic system


a stainless steel column 25 cm x 4.6 mm,packed with
A. Determine by infrared absorption spectrophotometry (2.4.6).
octadecylsilane bonded to porous silica (5 Ilm),
Compare the spectrum with that obtained with ormeloxifene
mobile phase: 80 volumes of acetonitrile and 20 volumes
hydrochloride RS orwith the reference spectrum oformeloxifene.
of water containing 0.04 per cent w/v solution of
B, When examined in the range 230 urn to 360 run (2.4.7), a tetramethylammonium hydroxide adjusted to pH 7.6
0.01 per cent w/v solution in methanol shows absorption with phosphoric acid, . .
maxima at about 278 and 282 urn. flow rate. 1.5 ml per minute,
C. Determine by thin-layer chromatography (2.4.17), coating spectrophotonieter set at 280 run,
the plate with silica gel G injection volume. 20 Ill.

Mobile phase. A mixture of 90 volumes of chloroform and Inject the reference solution and use an attenuation such that
10 volumes of methanol. the response for theprincipal peak due to trans-ormeloxifene
hydrochloride is more than 50 per cent of the full-scale
Test solution. Dissolve 0.25 g of the substance under
deflection ofthe recorder. Make a total ofsix injections. When
examination in 100 ml of chloroform.
the chromatograms are recorded under the conditions
Reference solution. A 0.25 per cent w/v solution of described above, trans-ormeloxifene hydrochloride is eluted
ormeloxifene hydrochloride RS in chloroform. before cis-ormeloxifene hydrochloride.The test is not valid
Apply to the plate 2 III of each solution. After development, unless the relative standard deviation ofsix replicate injections
dry the plate in air, until the odour ofthe solvents is no longer is not greater than 6 per cent and the resolution between the
detectable and spray with a 0.3 per cent w/v solution of peaks due to cis-ormeloxifene hydrochloride and trans-
potassium permanganate. The principal spot in the ormeloxifene hydrochloride is greater than 1. If necessary,
chromatogram obtained with the test solution corresponds to adjust the proportions and the flow rate of the mobile phase
that in the chromatogram obtained with the reference solution. to obtain proper resolution. Inject a suitable volume of test
solutiop and record the response. From the average peak areas
D. To 1 ml ofa 2 per centw/v solution in ethanol (95 percent)
of the six replicate analyses calculate the content of trans-
add 1 ml of a saturated solution of picric acid in water, stir
ormeloxifene hydrochloride and cis-ormeloxifene
well and set aside for 5 minutes. The yellow precipitate obtained
hydrochloride in the substance under examination by
after washing with water and drying at 60° for 4 hours melts at
comparing with the peak responses for trans-ormeloxifene
212°to 218°(2.4.21).
hydrochloride and cis-ormeloxifene hydrochloride respectively
Tests obtained with reference solution.
Total basic substances. Weigh accurately 0.5 g, dissolve in Storage. Store protected from moisture.
25 ml of anhydrous glacial acetic acid, add 10 ml of a 5 per
cent w/v solution of mercuric acetate in anhydrous glacial
acetic acid. Titrate with 0.1 M perchloric acid, using clystal
violet solution as indicator to a bluish green end-point. Carry Ormeloxifene Hydrochloride Tablets
out a blank titration.
Centchroman Hydrochloride Tablets; Centchroman
1 ml of 0.1 M perchloric acid is equivalent to 0.04935 g of Tablets
C30H3sN03,HCl.
Ormeloxifene Hydrochloride Tablets contain not less than
cis~Isomer.Not more than 1.5 per cent ofthe total content of 90.0 per cent and not more than 110.0 per cent of the stated
hydrochlorides of trans-and cis-isomers determined in the amount ofOrmeloxifene hydrochloride, C30H3sN03,HCI.
Assay.
Usual strength. 30 mg.
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Loss on drying (2.4.19). Not more than 3.5 per cent, determined Identification
on 1.0 g by drying in an oven at 105° for 4 hours.
Shake a quantity of the powdered tablets containing 0.1 g of
Assay. Determine by liquid chromatography (2.4.14). Ormeloxifene Hydrochloride with! 0 ml of chloroform, filter
Test solution.. A 0.004 per cent w/v solution of the substance and evaporate the filtrate to dryness at a pressure not
under examination in the mobile phase. exceeding 0.7 kPa. The residue complies with the following
Reference solution. A solution containing 0.004 per cent w/v tests.
of trans-ormeloxifene hydrochloride RS and 0.0006 per cent A. Determine by infrared absorption spectrophotometry (2.4.6).
w/v of cis-ormeloxifene hydrochloride RS in the mobile phase. Compare the spectrum with that obtained with ormeloxifene

1822
IP 2010 ORNlDAZOLE

hydrochloride RS or with the reference spectrum of Chromatographic system


ormeloxifene. a stainless steel column 25 cm x 4.6 mm, packed with
B. When examined in the range 230 nm to 360 nm (2.4.7), a octadecylsilane bonded to porous silica (5 Ilm),
mobile phase: 80 volumes of acetonitrile and 20 volumes
0.01 per cent w/v solution in methanol shows absorption
maxima at about 278 and 282 nm. of water containing 0.04 per cent w/v solution of
tetramethylammonium hydroxide adjusted to pH 7.6
C. Determine by thin-layer chromatography (2.4.17), coating with phosphoric acid,
the plate with silica gel G - flow rate. 1.5 ml per minute,
Mobile phase. A mixture of 90 volumes of chloroform and - spectrophotometer set at 280 nm,
10 volumes of methanol. injection volume. 20 Ill.
Inject the reference solution and use an attenuation such that
Test solution. Dissolve 0.25 g of the substance under
the response for the principal peak due to trans-ormeloxifene
examination in 100 ml of chloroform.
hydrochloride is more than 50 per cent offull-scale deflection
Reference solution. A 0.25 per cent w/v solution of of the recorder. Make a total of six injections. When the
ormeloxifene hydrochloride RS in chloroform. chromatograms are recorded under the conditions described
Apply to the plate 2 III of each solution. After development, above, trans-ormeloxifene hydrochloride is eluted before cis-
dry the plate in air, until the odour of the solvents is no longer ormeloxifene hydrochloride.The test is not valid unless the
detectable and spray with ~ 0.3 per cent w/v solution of relative standard deviation of six replicate injections is not
potassium permanganate. The principal spot in the greater than 6 per cent and the resolution between the peaks
chromatogram obtained with the test solution corresponds to due to cis-ormeloxifene hydrochloride and trans-ormeloxifene
that in the chromatogram obtained with the reference solution. hydrochloride is greater than 1. If necessary, adjust the
proportions and the flow rate of the mobile phase to obtain
Tests proper resolution. Inject a suitable volume of test solution
and record the response. From the average peak areas of the
Dissolution (2.5.2).
six replicate analyses calculate the content of trans-
Apparatus No.2, ormeloxifene hydrochloride and cis-ormeloxifene
Medium. 900 ml of water, hydrochloride in the substance under examination.
Speed and time. 100 rpm and 45 minutes.
Storage. Store protected from moisture.
Withdraw a suitable volume ofthe medium , and filter. Measure
the absorbance of the filtrate, suitably diluted if necessary, at
the maximum at about 278 nm (2.4.7). Calculate the content of Ornidazole
C30H3sN03,HCl in the medium from the absorbance obtained
OH
from a solution of known concentration of Ormeloxifene
hydrochloride RS in water. ~CI
D. Not less than 70 per cent of the stated amount of
C30H3sN03,HCl. 02N~rCH3
cis-Isomer. Not more than 1.5 per cent ofthe total content of
ormeloxifene hydrochlorides of trans- and cis-isomers C7HIQClN30 3 Mol. Wt. 219.6
determined in the Assay. Omidazole is (RS)-I-chloro-3-(2-methyl-5-nitroimidazol-l-
Other tests. Comply with the tests stated under Tablets. yl)propan-2-ol.
Omidazole contains not less than 98.0 per cent and not more
Assay. Determine by liquid chromatography (2.4.17).
than 101.0 p~r cent ofC7H IQClN30 3,calculated on the anhydrous
Test solution. Weigh and powder 20 tablets. Shake a quantity basis.
ofthe powder containing 0.1 g ofOrmeloxifene Hydrochloride Category. Antiamoebic.
with three quantities, each of 5 ml, of methanol, centrifuge
Dose. 500 mg twice a day orally for five days.
each extract, dilute the combined extracts to 25 ml with
methanol and then dilute 250 III ofthe resulting solution to 25 Description. A white to yellowish white crystalline powder.
ml with the mobile phase. Identification
Reference solution. A solution containing 0.004 per cent w/v A. Determine by infrared absorption spectrophotometry (2.4.6).
of trans-ormeloxifene hydrochloride RS and 0.0006 per cent Compare the spectrum with that obtained with ornidazole RS
w/v of cis-ormeloxifene hydrochloride RS in the mobile phase. or with the reference spectrum of omidazole.

1823
ORNIDAZOLE IP 2010

B. When examined in the range 230 nm to 360 nm (2.4.7), a Storage. Store protected from light and moisture, at a
0.002 per cent w/v solution in 0.1 M hydrochloric acid shows temperature not exceeding 30°.
an absorption maximum at about 277 nm; absorbance at
277 nm, 0.580 to 0.630.

Tests Ornidazole Tablets


Ornidazole Tablets contain not less than 95.0 per cent and not
Related substances. Determine by liquid chromatography
more than 105.0 per cent of the stated amount of ornidazole,
(2.4.14).
C7H IOCIN30 3•
Test solution. Dissolve 25 mg of the substance under
Usual strength. 500 mg.
examination in 25.0 ml ofthe mobile phase.
Reference solution (a). A 0.001 per cent w/v solution of Identification
2-methyl-5-nitroimidazole RS in the mobile phase. Extract a quantity ofthe powdered tablets containing 0.1 g of
Reference solution (b). A 0.001 per cent w/v solution of Ornidazole with 40 ml of chloroform, filter and evaporate the
ornidazole RS in the mobile phase. filtrate to dryness. The residue complies with the following
test.
Reference solution (c). Dilute 20.0 ml ofreference solution (a)
and 1.0 ml ofreference solution (b) to 200.0 ml with the mobile A. Determine by infrared absorption spectrophotometry (2.4.6).
phase. Compare the spectrum with that obtained with ornidazole RS
or with the reference spectrum of ornidazole.
Chromatographic system .
- a stainless steel column 25 cm x 4.6 mID, packed with B. Heat a quantity ofthe powdered tablets containing 0.1 g of
octadecylsilane bonded to porous silica (5 /lm), Ornidazole with 10 mg of zinc powder, 1 ml of water and
- mobile phase: a mixture of 70 volumes of O.OlM 0.25 m1 hydrochloric acid for 5 minutes, cool in ice, add 0.5 ml
potassium dihydrogen orthophosphate and 30 of sodium nitrite solution and remove the excess of nitrite
volumes of methanol, with sulphuric acid. Add 0.5 ml of 2-naphthol solution and 2
- flow rate. 1 ml per minute, ml of5 M sodium hydroxide solution. An orange-red colour is
- spectrophotometer set at 318 nm, produced.
- injection volume. 20 Ill. Tests
Inject reference solution (c). The test is not valid unless the
Dissolution (2.52).
resolution between the peaks corresponding to 2-methyl-5-
Apparatus No. 1,
nitroimidazole and ornidazole is at least 1.5.
Medium. 900 ml of 0.1 M hydrochloric acid,
Inject the test solution, reference solutions (a) and (b). In the Speed and time. 75 rpm and 30 minutes.
chromatogram obtained with the test solution, the area of any
Withdraw a suitable volume ofthe medium and filter promptly,
peak corresponding to 2-methyl-5-nitroimidazole is not more
rejecting the first few ml of the filtrate and dilute a suitable
than 0.2 times the area of the peak obtained with reference
volume ofthe filtrate with 0.1 M hydrochloric acid. Measure
solution (a) (0.2 per cent) and the sum of areas of all the
the absorbance of the resulting solution at the maximum at
secondary peaks is not more than the area of the peak in the
about 277 nm (2.4.7). Calculate the content of ornidazole,
chromatogram obtained with reference solution (b)
C7H IOCIN30 3 in the medium from the absorbance obtained from
(1.0 per cent).
a solution of known concentration of ornidazole RS
Heavy metals (2.3.13). 1.0 g complies with the limit test for
D. Not less than 80 per cent of the stated amount of
heavy metals, Method B (20 ppm).
C7H IOCIN30 3•
Sulphated ash (2.3.18). Not more than 0.1 per cent. Related substances. Determine by liquid chromatography
Water (2.3.43). Not more than 1.0 per cent, determined on 0.5 g. (2.4.14).
Assay. Weigh accurately about 0.15 g, dissolve in 50 ml of Test solution. Disperse a quantity of the powdered tablets
glacial acetic acid. Titrate with 0.1 M perchloric acid, containing 25 mg ofornidazole in 25.0 m1 of the mobile phase.
determining the end-point potentiometrically (2.4.25). Carry Reference solution (a). A 0.001 per cent w/v solution of
out a blank titration. 2-methyl-5-nitroimidazole RS in the mobile phase.
1 ml of 0.1 M perchloric acid is equivalent of 0.02196 g of Reference solution (b). A 0.001 per cent w/v solution of
C7H IOCIN30 3. ornidazole RS in the mobile phase.

1824
IP 2010 ORPHENADRINE CITRATE

Reference solution (c). Dilute 20.0 ml ofreference solution (a) Orphenadrine Citrate contains not less than 98.5 per cent and
and 1.0 ml ofreference solution (b) to 200.0 ml with the mobile not more than 101.0 per cent ofC 1sH 23NO, C6H s0 7, calculated
phase. on the dried basis.
Chromatographic system Category. Skeletal muscle relaxant.
- a stainless steel column 25 cm x 4.6 mm, packed with
Dose. By intramuscular or by slow intravenous injection (over
octadecylsilane bonded to porous silica (5 11m),
5 minutes), 60 mg repeated after 12 hours if necessary.
- mobile phase: a mixture of 70 volumes of 0.01 M
potassium dihydrogen orthophosphate and 30 volumes Description. A white or almost white, crystalline powder;
of methanol, odourless or almost odouriess.
- flow rate. 1 ml per minute,
spectrophotometer set at 318 nm, Identification
- injection volume. 20 Ill. Test A may be omitted if tests B, C, D and E are carried out.
Inject reference solution (c). The test is not valid unless the Tests B, C and D may be omitted if tests A and E are carried
resolution between the peaks corresponding to 2-methyl-5- out.
nitroimidazole and omidazole is at least 2.0. A. Determine by infrared absorption spectrophotometry,(2.4.6).
Inject the test solution, reference solution (a) and (b). In the Compare the spectrum with that obtained with orphenadrine
chromatogram obtained with the test solution, the area ofany citrate RS.
peak corresponding to 2-methyl-5-nitroimidazole is not more B. When examined in the range 230 nm to 360 nm (2.4.7), a
than 0.2 times the area of the peak obtained with reference 0.06 per cent w/v solution in ethanol (95 per cent) shows
solution (a) (0.2 per cent) and the sum of areas of all the
secondary peaks is not more than the area of the peak in the
absorption maxima at 258 nm, 264 mnand 271 nm; absorbances
at the maxima are about 0.68, 0.72 and 0.47 respectively.
chromatogram obtained with the reference solution (b) (1.0
per cent). C. Dissolve 50 mg in 10 ml of ethanol (50 per cent), add 10 ml
of picric acid solution and allow to stand. The precipitate
Other tests. Comply with the tests stated under Tablets. after recrystallisation from ethanol (95 per cent), melts at
Assay. Weigh and powder 20 tablets. Weigh accurately a about 89° or at about 107° (2.4.21).
quantity ofthe powder containing 0.2 g ofOmidazole, transfer D. Dissolve 5 mg in 2 ml of sulphuric acid; an orange-red
to a sintered-glass crucible and extract with 10 ml of hot colour is produced.
acetone. Repeat the extraction 6 times with hot acetone. Cool,
add to the combined extracts 50 ml of acetic anhydride. Titrate E. To 1 g add 10 ml water and 2 ml of 5 M sodium hydroxide,
with 0.1 M perchloric acid, determining the end point shake with two quantities, each of 10 ml, of chloroform and
potentiometrically (2.4.25). Carry out a blank titration. discard the chloroform. Heat the aqueous solution to boiling
with an excess of mercuric sulphate solution, filter ifnecessary
1 ml of 0.1 M perchloric acid is equivalent to 0.02196 g of and boil the resulting solution with 0.2 ml of dilute potassium
C7H IOClN30 3• permanganate solution; the solution is decolorised and a
Storage. Store protected from ligh! and moisture, at a white precipitate is produced.
temperature not exceeding 30°.
Tests
Quaternary ammonium salt. Determine by thin-layer
Orphenadrine Citrate chromatography (2.4.17), coating the plate with silica gel G.
Mobile phase. A mixture of 50 volumes of 2-propanol,
30 volumes of butyl acetate. 15 volumes of water and
5 volumes of strong ammonia solution.
HO eOOH Test solution. Dissolve 0.1 g of the substance under
, Hooe~eooH examination in 10 ml methanol.
Reference solution. A 0.005 per cent wlv solution of
ethyldimethyl [2-(2-methylbenzhydryloxy)ethyl ]ammonium
Mol. Wt. 461.5 chloride RS.
Orphenadrine Citrate is (RS)-dimethyl[2-(2- Apply to the plate 5 III of each solution. After development,
methylbenzhydryloxy)ethyl]amine dihydrogencitrate. dry the plate in air and spray with dilute potossium

1825
ORPHENADINE CITRATE IP 2010

iodobismuthate solution. Any spot corresponding to Description. A white or almost white, crystalline powder;
ethyldimethyl [2-(2-methylbenzhydryloxy) ethyl] ammonium odourless or almost odourless.
chloride in the chromatogram obtained with the test solution
is not more intense than the spot in the chromatogram obtained Identification
with the reference solution. Tests A andF may be omitted iftestsB, C, D andE are carried
Secondary amine. Determine by thin-layer chromatography out. Tests B, C and D may be omitted iftests A, E and Fare
(2.4.17) coating the plate with silica gel GF254. carried out.
Mobile phase. A mixture of 96 volumes of I-butanol and A. Determine by infrared absorption spectrophotometry,(2.4.6).
4 volumes of strong ammonia solution. Compare the spectrum with that obtained with orphenadrine
hydrochloride RS.
Test solution. Dissolve 0.4 g of the substance under
examination in'l 0 ml methanol. B. When examined in the range 230 nm to 360 nmJ2.4.7), a
0.06 per cent wlv solution in ethanol (95 per cent) shows
Reference solution. A 0.02 per cent wlv solution of methyl [2-
three absorption maxima at about 258 nm,264nm and 271 nm;
(2-methylbenzhydlyloxy) ethyl]amine hydrochloride R8.
absorbances at the maxima, about 1.07, 1.13 and 0.73
Apply to the plate 10 /!l of each solution. After development, respectively.
dry in air and examine in ultra-violet light at 254 nm. Spray the
C. Dissolve about 5 mg in 2 mlof sulphuric acid; an orange-
plate with dilute potassium iodobismuthate solution and
red colour is produced.
examine again. By each method of visualisation any spot
corresponding to methyl [2-(2-methylbenzhydryloxy) D. Dissolve about 50 mg inl0 ml of ethanol (95percent), add
ethyl]amine hydrochloride in the chromatogram obtained with 10 ml of picric acid solution and allow to stand. The
the test solution is not more intense than the spot in the precipitate, after recrystallisation from ethanol (95 per cent)
chromatogram obtained with the reference solution. melts at about 89° or at about 107° (2.4.21).
Heavy metals (2.3.13). 2.0 g complies with the limit test for Tests
heavy metals, Method B (10 ppm). Use 2 ml oflead standard
solution (l0 ppm Pb) to prepare the standard. Quaternary ammonium salt. Determine by thin-layer
chromatography (2.4.17), coating the plate with silica gel G.
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Mobile phase. A mixture of 50 volumes of 2-propanol,
Loss on drying (2.3.19). Not more than 0.5 per cent, determined
30 volumes of butyl acetate, 15 volumes of water and
on 1.0 g by drying in an oven at 105° for 3 hours.
5 volumes of strong ammonia solution.
Assay. Weigh accurately about 1.0 g, dissolve in 30 ml of
Test solution. Dissolve 0.1 g of the substance under
anhydrous glacial acetic acid. Titrate with 0.1 M perchloric
examination in 10 ml of methanol.
acid, determining the end-point potentiometrically (2.4.25).
Carry out a blank titration. Reference solution. A 0.005 per cent wlv solution of
ethyldimethyl [2-(2-methylbenzhydryloxy) ethyl] ammonium
1 ml of 0.1 M perchloric acid is equivalent to 0.04615 g of
chloride R8.
C 1sH23NO, C6Hs07.
Apply to the plate 5 /!l of each solution. After development,
Storage. Store protected from light.
dry the plate in air and spray with dilute potassium
iodobismuthate solution. Any spot corresponding to
ethyldimethyl [2-(2-methylbenzhydryloxy) ethyl] ammonium
Orphenadrine Hydrochloride chloride in the chromatogram obtained with the test solution
is not more intense than the spot in the chromatogram obtained
C 1sH23NO,HCl Mol. Wt.305.8 with the reference solution.
Orphenadrine Hydrochloride is (RS)-dimethyl[2- Secondary amine. Determine by thin-layer chromatography
(2methylbenzhydryloxy) ethyl]amine hydrochloride. (2.4.17) coating the plate with silica gel GF254.
Orphenadrine Hydrochloride contains not less than 98.5 per Mobile phase. A mixture of 96 volumes of I-butanol and
cent and not more than 101.0 percent of C 1sH 23NO,HCl. 4 volumes of strong ammonia solution.
calculated on the dried basis.
Test solution. Dissolve 0.4 g of the substance under
Category. Antiparkinsonian. examination in 10 ml of methanol.
Dose. 150 mg daily, in divided doses, gradually increased; Reference solution. A 0.02 per cent wlv solution of methyl [2-
maximum 400 mg daily. (2-methylbenzhydryloxy) ethyl]amine hydrochloride R8.

1826
IP 2010 OSELTAMIVIR PHOSPHATE

Apply to the plate 10 III of each solution. After development, Assay. Weigh and powder 20 tablets. Weigh accurately a
dry in air and examine in ultra-violet light at 254 nm. Spray the quantity ofthe powder containing about 70 mg Orphenadrine
plate with dilute potassium iodobismuthate solution and Hydrochloride and dissolve as completely as possible in a
examine again. By each method of visualisation any spot mixture of 5 ml of water and 5 ml of 2 M hydrochloric acid
corresponding to methyl [2-(2-methylbenzhydryloxy) Without delay extract with four quantities, each 15 ml, of
ethyl]amine hydrochloride in the chromatogram obtained with chloroform, filter the combined extracts and evaporate to about
the test solution is not more intense than the spot in the 20 m1. Add 30 ml of anhydrous glacial acetic and 2 ml of
chromatogram obtained with the reference solution. mercuric acetate solution and titrate with 0.02 M perchloric
Heavy metals (2.3.13). 2.0 g complies with the limit test for acid determining the end point potentiometrically (2.4.25).
heavy metals, Method B (10 ppm). Use 2 ml oflead standard Carry out a blank titration.
solution (10 ppm Pb) to prepare the standard. I ml of 0.02 Mperchloric acid is equivalent to 0.006117 g of
Sulphated ash (2.3.18). Not more than 0.1 percent. C 1SH23NO,HCI.

Loss on drying (2.3.19). Not more than 0.5 per cent, determined Storage. Store protected from light and moisture.
on 1.0 g by drying in an oven at 105° for 3 hours.
Assay. Weigh accurately about 1.0 g, dissolve in 20 ml of
anhydrous glacial acetic acid, add 20 ml of mercuric acetate Oseltamivir Phosphate
solution and titrate with 0.1 M perchloric acid using
l-naphtholbenzein solution as indicator. Carry out a blank
titration.
1 ml of 0.1 M perchloric acid is equivalent to 0.03058 g of
C 1sH23NO, HCI.
Storage. Store protected from light.

Orphenadrine Tablets CI6H2SN204, H3P04 Mol. Wt. 410.4

Orphenadrine Hydrochloride Tablets Oseltamivir Phosphate is phosphoric acid salt of ethyl


(3R,4R,5S)-4-(acetylamino)-5-amino-3-(1-ethylpropoxy)-I-
Orphenadrine Tablets contain not less than 92.5 per cent and cyclohexene-l-carboxylate.
not more than 107.5 per cent of the stated amount of
orphenadrine hydrochloride, C 1SH23NO,HCI. Oseltamivir Phosphate contain not less than 98.0 per cent and
not more than 102.0 per cent ofCI6H2sN204 .H3P0 4,calCulated
Usual strength. 50 mg. on the dried basis.
Identification Category. Antiviral.
Extract a quantity of the powdered tablets containing about Description. A white or off-white powder.
0.15 g ofOrphenadrine Hydrochloride with chloroform, filter
and evaporate the filtrate to dryness. The residue complies Identification
with the following tests. A. Determine by infrared absorption spectrophotometry (2.4.6).
A. Dissolve· 5 mg in 2 ml of sulphuric acid; an orange-red Compare the spectrum with that obtained with oseltamivir
colour is produced. phosphate RS.
B. Dissolve 50 mg in 10 ml of ethanol (50 per cent), add 10 ml B. In the Assay, the principal peak in the chromatogram
of picric acid solution and allow to stand. The precipitate obtained with the test solution corresponds to the peak in the
after recrystallisation from ethanol (95 per cent), melts at chromatogram obtained with the reference solution.
about 89° or at about 107°(2.4.21).
Tests
C. A 5 per cent w/v solution gives reaction A of chlorides
(2.3.1). Specific optical rotation (2.4.22). - 42.0° to - 48.0°, determined
in a 1.0 per cent w/v solution in methanol.
Tests
Related substances. Determine by liquid chromatography
Other tests. Comply with the tests stated under Tablets. (2.4.14).

1827
OSELTAMIVIR PHOSPHATE IP 2010

NOTE - Prepare the solutions immediately before use. Chromatographic system


a stainless steel column 15 cm x 4.6 mm, packed with
Test solution. Dissolve 25 mg of the substance under
octylsilanebonded to porous silica (5 flm) (Such as
examination in 25 ml ofthe mobile phase.
YMC pack PRO C8),
Reference solution (a). A 0.1 per cent w/v solution of - column temperature. 50°,
oseltamivir phosphate RS in the mobile phase. - mobile phase: a mixture of66 volumes of buffer solution
Reference solution (b). Dilute 1 ml ofreference solution (a) to prepared by dissolving 6.8 g of anhydrous monobasic
100 ml with the mobile phase. potassium phosphate in 1000 ml of water, adjusting the
pH to 6.0 with dilute sodium hydroxide, 24.5 volumes
Chromatographic system of methanol and 23.5 volumes of acetonitrile,
- a stainless steel column 15 cm x 4.6 mm, packed with flow rate. 1 ml per minute,
octylsilane bonded to porous silica (5 flm) (such as YMC spectrophotometer set at 207 nm,
pack PRO C8), - injection volume. 20 fll.
- column te~perature 50°,
- mobile phase: a mixture of66 volumes ofa buffer solution Inject the reference solution. The test is not valid unless the
prepared by dissolving 6.8 g of anhydrous monobasic tailing factor is not more than 2.0, the column efficiency in not
potassium phosphate in 1000 ml of water and adjusting less than 2000 theoretical plates and the relative standard
the pH to 6.0 with dilute sodium hydroxide, 24.5 volumes deviation for replicate injections is not more than 2.0 per cent.
of methanol and 23.5 volumes of acetonitrile, Inject the test solution and the reference solution.
- flow rate. 1 ml per minute,
- spectrophotometer set at 207 nm, Calculate the content ofC16H28N204,H3P04'
injection volume. 20 fll. Storage. Store protected from light and moisture.
Inject reference solution (a). The test is not valid unless the
column efficiency is not less than 2000 theoretical plates and
the tailing factor is not more than 2.0. Oseltamivir Capsules
Inject the test solution and reference solution (b). In the Oseltamivir Phosphate Capsules
chromatogram obtained with the test solution, the area of any Oseltamivir Capsules contain not less than 90.0 per cent and
secondary peak is not more than 0.5 times the area ofthe peak not more than 110.0 per cent of the stated amount of
in the chromatogram obtained with the reference solution (b) oseltamivir, C16H28N204.
(0.5 per cent) and the sum of all the secondary peaks is not
more than the area of the peak in the chromatogram obtained Usual strength. 75 mg.
with the reference solution (b) (1.0 per cent).
Identification
Phosphoric acid. 23.4 to 24.4 per cent, calculated on a dried
basis. In the Assay, the principal peak in the chromatogram obtained
with the test solution corresponds to the peak in the
Weigh accurately about 0.2 g and dissolve in 40 ml ofdistilled chromatogram obtained with the reference solution.
water. Titrate with 0.1 M sodium hydroxide, determining the
end-point potentiometrically (2.4.25). Carry out a blank titration. Tests
1 ml of 0.1 M sodium hydroxide is equivalent to 0.0049 g of Dissolution (2.5.2).
phosphoric acid. Apparatus No.1,
Heavy metals (2.3.13). 1 g complies with the limit test for heavy Medium. 900 ml of 0.1 M hydrochloric acid,
metals, Method A (20 ppm). Speed and time. 50 rpm and 45 minutes
Loss on drying (2.4.19). Not more than 0.5 per cent, determined Withdraw a suitable volume ofthe medium and filter. Determine
on 1 g by drying in an oven at 105°. by liquid chromatography (2.4.14).
Assay. Determine by liquid chromatography (2.4.14). Test solution. Use the filtrate.
Test solution. Dissolve 50 mg of the substance under Reference solution. Dissolve 50 mg of oseltamivirphosphate
examination in 50.0 ml ofthe mobile phase. Dilute 10.0 ml of RS in 20 ml ofthe mobile phase and dilute to 100 ml with the
the solution to 50.0 ml with the mobile phase. dissolution medium. Dilute 5 ml ofthe solution to 25 ml with
Reference solution. A 0.02 per cent w/v solution of oseltamivir the dissolution medium.
phosphate RS in the mobile phase. Use the chromatographic system described under Assay.

1828
IP 2010 OSELTAMIVIR ORAL SUSPENSION

D. Not less than 80 per cent of the stated amount of mobile phase: a mixture of66 volumes ofa buffer solution
C16H2sN204' prepared by dissolving 6.8 g of anhydrous monobasic
potassium phosphate in 1000 ml of water and adjusting
Related substances. Determine by liquid chromatography
the pH to 6.0 with dilute sodium hydroxide, 24.5 volumes
(2.4.14).
of methanol and 23.5 volumes of acetonitrile,
NOTE - Prepare the solutions immediately before use. - flow rate. 1.2 ml per minute,
Test solution. Weigh accurately a quantity of the mixed spectrophotometer set at 207 nm,
contents of20 capsules containing about 50 mg ofoseltamivir, - injection volume. 20 /-ll.
disperse in 50 ml ofmobile phase and filter. Inject the reference solution. The test is not valid unless the
Reference solution (a). A 0.1 per cent w/v solution of tailing factor is not more than 2.0, the column efficiency is not
oseltamivir phosphate RS in the mobile phase. less than 2000 theoretical plates and the relative standard
deviation for replicate injections is not more than 2.0 per cent.
Reference solution (b). Dilute 1 ml of reference solution to
100 ml with the mobile phase. Inject the test solution and the reference solution.

Chromatographic system Calculate the content ofC16H2sN204.


- a stainless steel column 25 cm x 4.6 rom, packed with Storage. Store protected from moisture, at a temperature not
octylsilane bonded to porous silica (5 /-lm) (such as YMC exceeding 30°.
pack PRO C8),
mobile phase: a mixture of66 volumes ofa buffer solution Labelling. The label states the strength in terms of the
prepared by dissolving 6.8 g of anhydrous monobasic equivalent amount of oseltamivir.
potassium phosphate in 1000 ml of water, adjusting the
pH to 6.0 with dilute sodium hydroxide, 24.5 volumes
of methanol and 23.5 volumes of acetonitrile, Oseltamivir Oral Suspension
- flow rate. 1.5 ml per minute,
spectrophotometer set at 207 nm, Oseltamivir Phosphate Oral Suspension
injection volume. 20 /-ll.
Oseltamivir Oral Suspension is a mixture consisting of
Inject reference solution (a). The test is not valid unless the Oseltamivir phosphate with buffering agents and other
column efficiency is not less than 2000 theoretical plates and excipients. It contains a suitable flavouring agent. It is filled in
the tailing factor is not more than 2.0. a sealed container.
Inject the test solution and reference solution (b). In the The suspension is constituted by dispersing the contents of
chromatogram obtained with the test solution, the area of any the sealed container in the specified volume of water just
secondary peak is not more than the area of the peak in the before issue.
chromatogram obtained with the reference solution (b) (1.0
Oseltamivir Oral Suspension contains not less than 90.0 per
per cent) and the sum of the areas of all the secondary peaks
cent and not more than 110.0 percent ofthe stated amount of
is not more than twice the area ofthe peak in the chromatogram
oseltamivir C16H2sN204.
obtained with the reference solution (b) (2.0 per cent).
The contents of the sealed container comply with the
Other tests. Comply with the tests stated under Capsules.
following requirement.
Water (2.3.43). Not more than 5.0 per cent, determined on 0.5 g.
Usual strength. 15 mg per mI.
Assay. Determine by liquid chromatography (2.4.14)..
Water (2.3.43). Not more than 2.5 per cent, determined on 1.0 g.
NOTE - Prepare the solutions immediately before use.
The constituted suspension complies with the requirements
Test solution. Weigh accurately a quantity of the mixed stated under Oral liquids and with the following
contents of20 capsules containing about 200 mg ofoseltamivir, requirements.
disperse in 100.0 mI ofthe mobile phase and filter. Dilute 5.0 ml
ofthe solution to 50.0 ml with the mobile phase. Identification
Reference solution. A 0.02 per cent w/v solution of oseltamivir A. In the Assay, the principal peak in the chromatogram
phosphate RS in the mobile phase. obtained with the test solution corresponds to the peak in the
Chromatographic system chromatogram obtained with reference solution (b).
- a stainless steel column 15 cm x 4.6 rom, packed with B. To 2 ml of the reconstituted suspension, add 2 ml of dilute
octylsilane bonded to porous silica (5 /-lm), nitric acid and 4ml ofa 10 per cent w/v solution of ammonium

1829
OSELTAMIVIR ORAL SUSPENSION IP 2010

molybdate and wann the solution. A bright yellow precipitate Chromatographic system
isfonned. a stainless steel column 15 cm x 4.6 mm, packed with
octy1silane bonded to porous silica (5 Ilm),
Tests mobile phase: a mixture of 60 volumes ofa buffer solution
prepared by dissolving 6.8 g of potassium dihydrogen
pH (2.4.24). 3.0 to 5.0.
phosphate in 1000 m1 of water and adjusting the pH to
Related substances. Detennine by liquid chromatography 6.0 with dilute sodium hydroxide, 24.5 volumes of
(2.4.14). methanol and 23.5 volumes of acetonitrile,
NOTE - Prepare the solutions immediately before use. flow rate. 1.2 ml per minute,
spectrophotometer set at 207 urn,
Test solution. Weigh accurately a quantity of the suspension injection volume. 20 Ill.
containing 25 mg ofoseltamivir, dissolve in 25 ml ofthe mobile
Inject the reference solution. The test is not valid unless the
phase and filter.
tailing factor is not more than 2.0, the column efficiency in not
Reference solution (a). A 0.1 per cent w/v solution of less than 2000 theoretical plates and the relative standard
oseltamivir phosphate RS in the mobile phase. deviation for replicate injections is not more than 2.0 per cent.
Reference solution (b). Dilute 1 ml ofreference solution (a) to Inject the test solution and the reference solution.
100 ml with the mobile phase.
Calculate the content of CI6HzsNz04'
Chromatographic system Storage. Store protected from moisture, at a temperature not
- a stainless steel column 25 cm x 4.6 mm, packed with exceeding 30°.
octylsilane bonded to porous silica (5 Ilm),
- column temperature 35°, Labelling. The label states (1) the quantity ofactive ingredient
- mobile phase: 70 volumes of a buffer solution prepared in tenns of the equivalent amount of oseltamivir; (b) the
by dissolving 6.8 g ofpotassium dihydrogen phosphate temperature of storage and the period during which the
in 1000 ml of water and adjusting the pH to 6.0 with constituted suspension may be expected to be satisfactory
dilute sodium hydroxide, 15 volumes of methanol and for use.
15 volumes of acetonitrile,
flow rate. 1.5 ml per minute,
spectrophotometer set at 207 urn, Oxazepam
injection volume. 20 Ill.
Inject reference solution (a). The test is not valid unless the
column efficiency is not less than 2000 theoretical plates and
the tailing factor is not more than 2.0.
Inject the test solution and reference solution (b). In the CI
chromatogram obtained with the test solution, the area of any
secondary peak is not more than the area of the peak in the
chromatogram obtained with the reference solution (b)
(1.0 per cent) and the sum of areas of all the secondary peaks
Mol. Wt. 286.7
is not more than 3 times the area of the peak in the
chromatogram obtained with 'the reference solution (b) Oxazepam is 7-chloro-3-hydroxy-5-phenyl-1,3-dihydro-2H-
(3.0 per cent). 1,4-benzodiazepin-2-one.

Other tests. Complies with the tests stated under Oral liquids. Oxazepam contains not less than 98.5 per cent and not more
than 101.0 per cent ofClsHIICINzOz, calculated on the dried
Assay. Detennine by liquid chromatography{2.4. 14). basis.
NOTE - Prepare the solutions immediately before use. Category. Anxiolytic.
Test solution. Weigh accurately a quantity of the suspension Dose. 15 to 30 mg, 2 to 3 times daily.
containing 60 mg of oseltamivir, dissolve in 250.0 ml of the
Description. A white or alrnostwhite, crystalline powder.
mobile phase and filter. Dilute 10.0 ml ofthe solution to 25.0 ml
with the mobile phase and filter. Identification
Reference solution. A 0.0125 per cent w/v solution of Test A may be omitted iftests B, C and D are carried out. Tests
oseltamivir phosphate RS in the mobile phase. Band D may be omitted if tests A and C are carried out.

1830
IP 2010 OXAZEPAM TABLETS

A. Detennine by infrared absorption spectrophotometry (2.4.6). Any secondary spot in the chromatogram obtained with test
Compare the spectrum with that obtained with oxazepam RS. solution (a) is not more intense than the spot in the-
B. Prepare the solutions immediately before use, protected chromatogram obtained with reference solution (c) and at most
./i·om light. one such spot is more intense than the spot in the
chromatogram obtained with reference solution (d). The test
Dissolve about 20 mg in sufficient ethanol (95 per cent) to is not valid unless the chromatogram obtained with reference
produce 100 ml. Dilute 10 ml of the solution to 50 ml with solution (b) shows two clearly separated spots.
ethanol (95 per cent) (solution A). Dilute 10 ml of solution A
to 100 ml with ethanol (95 per cent) (solution B). Sulphated ash (2.3.18). Not more than 0.1 per cent.

When examined in the range 230 nm to 360 urn (2.4.7), solution Loss on drying (2.4.19). Not more than 0.5 per cent, detennined
A shows an absorption maxjmum at about 316 nm. When on 1.0 g by drying in an oven at 105°at a pressure not exceeding
examined in the range 220 urn to 250 urn, solution B shows an 0.7kPa.
absorption maximum at about 229 nm; absorbance at about Assay. Weigh accurately about 0.25 g and dissolve in a mixture
229 nm, 1.220 to 1.300. of 10 m1 of anhydrous glacial acetic acid and 90 ml of acetic
C. In the test for Related substances, the principal spot in the anhydride and titrate with 0.1 M perchloric acid detennining
chromatogram obtained with test solution (b) corresponds to the end point potentiometrically (2.4.25). Carry out a blank
that in the chromatogram obtained with reference solution (b). titration.
D. Dissolve about 20 mg in a mixture of5 ml of hydrochloric 1 ml of 0.1 M perchloric acid is eqUivalent to 0.02867 g of
acid and 10 ml of wate/: Heat to boiling for 5 minutes and cool. ClsHIICIN202.
Add 2 ml of a 0.1 per cent w/v solution of sodium nitrite and Storage. Store protected from light and moisture.
allow to stand for 1 minute. Add 1 ml of a 0.5 per cent w/v
solution ofsulphamic acid, mix and allow to stand for 1minute.
Add 1 ml of 0.1 per cent w/v solution of a N- (i-naphthyl)
ethylenediamine dihydrochloride; a red colour is produced. Oxazepam Tablets
Tests Oxazepam Tablets contain not less than 90.0 per cent and not
more than 110.0 per cent of the stated. amount of oxazepam,
Related substances. Carry out the test protectedfrom light. ClsH11ClN202.
Detennine by thin-layer chromatography (2.4.17), coating the Usual strengths. 10 mg; 15 mg; 30 mg.
plate with silica gel GF254.
Identification
Wash the plate with methanol before use.
A. Extract a quantity of the powdered tablets containing
Mobile phase. A mixture of 100 volumes of dichloromethane
20 mg ofOxazepam with 25 ml of chloroform, filter, evaporate
and 10 volumes of methanol.
to dryness and dry the residue at 60° at a pressure not exceeding
Test solution (a). Dissolve 50 mg of the substance under 0.7kPa.
examination in sufficient acetone to produce 10m!.
On the residue, determine by infrared absorption
Test solution (b). Dilute 2 ml oftest solution (a) to 10 ml with spectrophotometry (2.4.6). Compare the spectrum with that
acetone. obtained with oxazepam RS or with the reference spectnnn of
Reference solution (a). Dissolve 10 mg of oxazepam RS in oxazepam.
sufficient acetone to produce 10 ml. B. When examined in the range 210 nm to 360 urn (2.4.7), the
Reference solution (b). Dissolve 10 mg each of oxazepam RS solution obtained in the Assay shows absorption maxima at
and bromazepam RS in sufficient acetone to produce about 230 nm and 316 nm.
lOml.
Tests
Reference solution (c). Dilute 1 ml ofreference solution (a) to
100 ml with acetone. Related substances. CarlY out the test protectedfrom light.
Reference solution (d). Dilute 5 ml ofsolution (d) to 10 m1 with Detennine by thin-layer chromatography (2.4.17) coating the
acetone. plate with silica gel GF 254. .
Apply to the plate 20 !J.I of each solution. Allow the mobile Wash the plate with methanol before use.
phase to rise 17 cm in the same direction as the washing with Mobile phase. A mixture of 100 volumes of dichloromethane
methanol. Dry in air and examine in ultraviolet light at 254 urn. and 10 volumes of methanol.

1831
OXAZEPAM TABLETS IP 2010

Test solution. Shake a quantity ofpowdered tablets containing Identification


30 mg ofOxazepam with 6 rnl ofacetone and centrifuge.
Determine by infrared absorption spectrophotometry (2.4.6).
Reference solution (a). Dilute 1 volume ofthe test solution to
Compare the spectrum with that obtained with oxcarbazepine
100 volumes with acetone.
RS or with the reference spectrum of oxcarbazepine.
Reference solution (b). Dilute 1 volume ofthe test solution to
500 volumes with acetone. Tests
Reference solution (c). A solution containing 0.1 per cent Related substances. Determine by liquid chromatography
w/v each of oxazepam RS and bromazepam RS. (2.4.14).
Apply to the plate 20 fl1 of each of the solutions. Allow the
Note - Use freshly prepared solutions.
mobile phase to rise 17 em in the same direction as in the
washing with methanol. Dry in air and examine in ultraviolet Test solution. Dissolve 50 mg of the substance under
light at 254 nm. Any secondary spot in the chromatogram examination in 100.0 ml ofthe mobile phase.
obtained with the test solution is not more intense than the Reference solution (a). A 0.05 per cent w/v solution of
spot in the chromatogram obtained with reference solution (a) oxcarbazepine RS in the mobile phase.
(1 per cent) and not more than one such spot is more intense
Reference solution (b). Dilute 1.0 ml ofreference solution (a)
than the spot in the chromatogram obtained with reference
to 100.0 ml with the mobile phase.
solution (b) (0.2 per cent). The test is not valid unless the
chromatogram obtained with reference solution (c) shows two Chromatographic system
clearly separated spots. a stainless steel column 25 em x 4.6 rom, packed with
octadecylsilane bonded to porous silica (5 flm) (such as
Otber tests. Comply with the tests stated under Tablets.
Inertsil C18),
Assay. Weigh and powder 20 tablets. Weigh accurately a - column temperature 50 0 ,
quantity of the powder containing about 25 mg of Oxazepam - mobile phase: a mixture of22 volumes of methanol, 16
and shake with 150 ml ofethanol (95 per cent) for 30 minutes. volumes of acetonitrile and 62 volumes of a buffer
Add sufficient ethanol (95 per cent) to produce 250.0 rnl and solution prepared by dissolving 6.8 g of potassium
centrifuge. Dilute 5.0 ml ofthe supernatant liquid to 100.0 ml dihydrogen orthophosphate in 1000 ml ofwater, adding
with the same solvent and measure the absorbance of the 2 ml of triethylamine and adjusting the pH to 6.0,
resulting solution at the maximum at about 230 nm (2.4.7). flow rate. 1.5 ml per minute,
Calculate the content of ClsHIIClNzOz taking 1250 as the - spectrophotometer set at 215 TIm,
specific absorbance at 230 TIm. injection volume. 10 fll.
Storage. Store protected from light at a temperature not
Inject reference solution (a). The test is not valid unless the
exceeding 30°.
column efficiency is not less than 2000 theoretical plates and
the tailing factor is not more than 2.0.
Oxcarbazepine Inject the test solution and reference solution (b). Run the
chromatograms for about 60 minutes~ The relative retention
times with reference to oxcarbazepine are· 1.7 for
dibenz[b,fJazepine-5-carboxylic acid amide (oxcarbazepine
impurity A), 7.9 for 10-methoxy-5H-dibenz[b,fJazepine
(oxcarbazepine impurity B), and 2.5 for 10-methoxy-5H-
dibenz[b,fJazepine-5-carboxylic acid amide (oxcarbazepine
impurity C ).
Calculate the contents of the impurities in the test solution
ClsHIZNzOz, Mol. Wt. 252.3 using the correction factors, 0.68 for oxcarbazepine impurity
Oxcarbazepine is 10,11-dihydro-1O-oxo-5H-dibenz[b,jJazepine- A, 0.76 for oxcarbazepine impurity Band 0.80 for oxcarbazepine
5-carboxarnide. impurity C. Not more than 1.0 per cent of oxcarbazepine
Oxcarbazepine contains not less than 98.0 per cent and not impurity A and not more than 0.1 per cent each of
more than 102.0 per cent ofClsHlzNzOz, calculated on the dried oxcatbazepine impurity Band oxcarbazepine impurity C and
basis. not more than 0.1 per cent ofany other impurity is found. The
Category. Non-opioid analgesics. sum of all the impurities is not more than 1.5 per cent.
Dose. 300 mg twice a day. Heavy metals (2.3.13). 1.0 g complies with the limit test for
Description. An off-white to yellow crystalline powder. heavy metals, Method B (20 ppm).

1832
IP 2010 OXCARBAZEPINE TABLETS

Sulphated ash (2.3.18). Not more than 0.1 per cent. D. Not less than 75 per cent of the stated amount of
Loss on drying (2.4.19). Not more than 0.5 per cent, determined ClsH12N202.
on 1.0 g by drying in an oven at 105 0 • Related substances. Determine by liquid chromatography
Assay. Determine by liquid chromatography (2.4.14) as (2.4.14).
described under related substances using the following Note - Useji-eshly prepared solutions.
solution.
Test solution (a). Weigh accurately a quantity ofthe powdered
Test solution. Dissolve 10 mg of the substance under tablets containing 50 mg of Oxcarbazepine add 15 ml methanol,
examination in 100.0 ml ofthe mobile phase.
mix with the aid of ultrasound for 15 minutes and dilute to
Reference solution. A 0.01 per cent w/v solution of 100.0 ml with methanol. Mix and centrifuge.
oxcarbazepine RS in the mobile phase.
Test solution (b). Dilute 5.0 ml of test solution (a) to 25.0 ml
Inject the reference solution. The test is not valid unless the with the mobile phase.
tailing factor is not more than 2.0, the column efficiency is not
less than 2000 theoretical plates and the relative standard Reference solution (a). Dissolve 25.0 mg of oxcarbazepine
deviation for replicate injections is not more than 2.0 per cent. RS in methanol with the aid ofultrasound and dilute to 50.0 ml
with methanol.
Inject the test solution and the reference solution.
Reference solution (b). Dilute 5.0 ml ofreference solution (a)
Calculate the content ofC,sH,2N202'
to 25.0 ml with the mobile phase.
Storage. Store protected from moisture.
Reference solution (c). Dilute 1.0 ml of reference solution (a)
to 100.0 ml with the mobile phase.

Oxcarbazepine Tablets Chromatographic system


a stainless steel column 25 cm x 4.6 mm, packed with
Oxcarbazepine Tablets contain not less than 90.0 per cent and octadecylsilane bonded to porous silica (5 Ilm) (Such
not more than 110.0 per cent of the stated amount of as Hypersil BDS CI8),
oxcarbazepine, ClsH12N202. column temperature 500 ,
Usual strengths. 150 mg; 300 mg; 450 mg; 600 mg. mobile phase: a mixture of 66 volumes of O.05M
potassium dihydrogen phosphate, 14 volumes of
Identification acetonitrile and 20 volumes of methanol, add 0.1 mlof
A. In the Assay, the principal peak in the chromatogram triethylamine and adjust the pH to 6.0 with.
obtained with the test solution (b) corresponds to the peak in orthophosphoric acid,
the chromatogram obtained with reference solution (b). flow rate. 2 ml per minute,
- spectrophotometer set at 215 hm,
B. Extract a quantity ofthe powdered tablets containing about
injection volume. 20 Ill.
50 mg ofoxcarbazepine with 100 ml with methanol and filter.
Diluted 2.0 ml ofthis solution to 100.0 ml with methanol. When Inject reference solution (a). The test is not valid unless the
examined in the range 200 urn to 350 nm (2.4.7), the solution column efficiency is not less than 2000 theoretical plates, the
shows an absorption maximum at about 254 nm. tailing factor is not more than 2.0 and relative standard deviation
for replicate injections is not more than 2.0 per cent.
Tests
Inject test solution (a) and reference solution (c). Run the
Dissolution (2.5.2). chromatograms for three times the retention time of the
Apparatus No. 1 principal peak. In the chromatogram obtained with the test
Medium. 900 ml of 0.75 per cent w/v solution ofsodium lauryl solution, the area of any secondary peak is not more than the
sulphate in water, area ofthe peak in the chromatogram obtained with reference
Speed and time. 75 rpm and 45 minutes. solution (c) (1.0 per cent) and the sum of areas of all the
Withdraw a suitable volume ofthe medium and filter. Measure secondary peaks is not more than twice the area ofthe peak in
the absorbance of the filtered solution, suitably diluted with the chromatogram obtained with reference solution (c) (2.0
the medium if necessary, at the maximum at about 305 urn per cent).
(2.4.7). Calculate the content of ClsH12N202 in the medium Other tests. Comply with the tests stated under Tablets.
from the absorbance obtained from a solution of known
Assay. Determine by liquid chromatography (2.4.14) as
concentration of oxcarbazepine RS prepared by dissolving
described under Related substances.
in minimum volume of methanol and then diluting with the
dissolution medium. Inject test solution (b) and reference solution (b).

1833
OXPRENOLOL HYDROCHLORIDE IP 2010

Calculate the contentofCIsHI2N202 in the tablets. Test solution (a). Dissolve 0.5 g of the substance under
examination in 10 rnl ofa mixture of90 volumes of chloroform
Storage. Store protected from moisture, at a temperature not
and 10 volumes of methanol.
exceeding 30°.
Test solution (b). Dissolve 0.5 g of the substance under
examination in 100 ml ofa mixture of90 volumes of chloroform
and 10 volumes of methanol.
Oxprenolol Hydrochloride
Reference solution (a). A 0.02 per cent w/v solution of the
OH H substance under examination in a mixture of 90 volumes of

o:
O~NyCH3 chloroform and 10 volumes of methanol.
I ,HCI Reference solution (b). A 0.01 per cent w/v solution of the
~ O~CH2 CH 3 substance under examination in a mixture of 90 volumes of
chloroform and 10 volumes of methanol.
C 1sH23N03,HCl Mol. Wt. 301.8
Reference solution (c). A 0.5 per cent w/v solution of
Oxprenolol Hydrochloride is (RS)-I-(2-allyloxyphenoxy)-3- oxprenolol hydrochloride RS in a mixture of 90 volumes of
isopropylaminopropan-2-01 hydrochloride. chloroform and 10 volumes of methanol.
Oxprenolol Hydrochloride contains not less than 98.5 per cent Apply to the plate 2 f.l.1 of each solution. Allow the mobile
and not more than 101.5 per cent ofClsH23N03,HCl, calculated phase to rise 13 em. Dry the plate in warm air for 10 minutes,
on the dried basis. allow to cool, spray with anisaldehyde solution, heat at 105°
Category. Beta-adrenoceptor antagonist (antihypertensive; for 10 minutes and examine in daylight. Any secondary spot
antianginal; antiarrhythmic). in the chromatogram obtained with test solution (a) is not
more intense than the spot in the chromatogram obtained
Dose. As antihypertensive, initially 80 mg twice daily, increased
with reference solution (a) and not more than one such spot is
as required at weekly intervals; maximum 480 mg daily. As
more intense than the spot in the chromatogram obtained
antianginal, 40 to 160 mg thrice daily. As antiarrhythmic, initially
with reference solution (b).
20 to 40 mg thrice daily, increased as necessary.
Heavy metals (2.3.13). 1.0 g complies with the iimit test for
Description. A white Of almost white, crystalline powder.
heavy metals, Method B (20 ppm).
Identification Sulphated ash (2.3 .18). Not more than 0.1 per cent.
Test A may be omitted if tests Band C are carried out. Test B Loss on drying (2.4.19). Not more than 0.5 per cent, determined
may be omitted if tests A and C are carried out. on 1.0 g by drying in an oven at 60° over phosphoruspentoxide
A. Determine by infrared absorption spectrophotometry (2.4.6). at a pressure of 1.5 to 2.5 kPa for 6 hours.
Compare the spectrum with that obtained with oxprenolol RS Assay. Weigh accurately about 0.25 g, dissolve in 60 ml of
or with the reference spectrum of oxprenolol. anhydrous glacial acetic acid, add 5 ml of mercuric acetate
B. In the test for Related substances, the principal spot in the solution. Titrate with 0.1 Mperchloric acid, determining the
chromatogram obtained with test solution (b) corresponds to end-point potentiometrically (2.4.25).Carry out a blank
that in the chromatogram obtained with reference solution (c). titration.

C. Gives reaction A ofchlorides (2.3.1). 1 ml of 0.1 M perchloric acid is equivalent to 0.03018 g of


C 1SH23N03,HCl.
Tests
Storage. Store protected from light and moisture.
Appearance ofsolution. A 10.0 per cent w/v solution in carbon
dioxide-free water is clear (2.4.1), and not more intensely
coloured than reference solution GYS6 (2.4.1).
Oxprenolol Tablets
pH (2.4.24). 4.5 to 6.0, determined in a freshly prepared
10.0 per cent wIv solution. Oxprenolol Hydrochloride Tablets
Related substances. Determine by thin-layer chromatography Oxprenolol Hydrochloride Tablets contain not less than
(2.4.17), coating the plate with silica gel G 95.0 per cent and not more than 105.0 per cent of the stated
Mobile phase. A mixture of 88 volumes of chloroform, amount of oxprenolol hydrochloride, CISH23N03,HCl. The
12 volumes of methanol and 2 volumes of strong ammonia tablets are coated.
solution. Usual strengths. 40 mg; 80 mg.

1834
IP 2010 OXYGEN 93 PER CENT

Identification Oxygen
A.To a quantity of the powdered tablets containing 50 mg of Mol. Wt. 32.0
Oxprenolol Hydrochloride add 10 ml of water and 2 ml of
Oxygen contains not less than 99.0 per cent vlv of Oz.
dilute sodium hydroxide solution, extract with 10 ml of
chloroform and reserve the aqueous layer for test C. Dry the This monograph applies to oxygen for medicinal use only.
chloroform extract over anhydrous sodium sulphate, filter and Description. A colourless gas; odourless.
evaporate the filtrate to dryness.
On the residue, determine by infrared absorption Identification
spectrophotometry (2.4.6). Compare the spectrum with that A. A glowing splinter of wood bursts into flame on contact
obtained with oxprenolol hydrochloride RS or with the with the gas.
reference spectrum of oxprenolol hydrochloride.
B. Shake with alkaline pyrogallol solution; the gas under
B. When examined in the range 230 nm to 360 nm (2.4.7), the examination is absorbed and the solution becoming dark
solution obtained in the Assay shows an absorption maximum brown.
only at about 273 nm.
C. When tested as described under Assay, not more than
C. The aqueous layer obtained in test A gives reaction A of 1.0 ml ofgas remains.
chlorides (2.3.1).
Tests
D. The residue obtained in test A melts at about 76° (2.4.21).
Carbon dioxide. Not more than 300 ppm vlv, determined by
Tests using a carbon dioxide detector tube (2.1.1).

Related substances. Determine by thin-layer chromatography Carbon monoxide. Not more than 5 ppm vlv, determined by
(2.4.17), coating the plate with silica gel G using a carbon monoxide detector tube (2.1.1).

Mobile phase. A mixture of 88 volumes of chloroform, Water vapour. Not more than 67 ppm vlv, determined by using
12 volumes of methanol and 2 volumes of strong ammonia a water vapour detector tube (2.1.1).
solution. Assay (2.3.33). Use 100 ml ofthe gas under examination and
Test solution. Extract a quantity of the powdered tablets place spirals of freshly cleaned copper wire and 125 ml of
containing 0.25 g of Oxpreno101 Hydrochloride with 5 ml of ammonia buffer pH 10.9 in the pipette. The volume of the
water, centrifuge and use the supernatant liquid. residual gas in the burette is not more than 1.0 m!.

Reference solution. Dilute 1 volume of the test solution to Storage. Store under pressure in metal cylinders of the type
200 volumes with water. conforming to the appropriate safety regulations. Valves and
taps should not be lubricated with oil or grease.
Apply to the plate 2 III of each solution. Allow the mobile
Labelling. The shoulder of the metal cylinder should be
phase to rise 13 cm. Dry the plate in warm air for 10 minutes,
painted white and the remainder should be painted black. The
allow to cool, spray with anisaldehyde solution, heat at 105°
cylinder should carry a label stating "Oxygen". In addition,
for 10 minutes and examine in daylight. Any secondary spot
"Oxygen" or the symbol "Oz" should be stencilled in paint on
in the chromatogram obtained with the test solution is not
the shoulder of the cylinder.
more intense than the spot in the chromatogram obtained
with the reference solution. .
Other tests. Comply with the tests stated under Tablets.
Assay. Weigh and powder 20 tablets. Weigh accurately a
Oxygen 93 Per Cent
quantity ofthe powder containing about 20 mg ofOxprenolol Oxygen 93 per Cent contains not less than 90.0 per cent and
Hydrochloride, add 25 ml of 0.1 M hydrochloric acid and not more than 96.0 per cent, vlv ofOz, the remainder consisting
sufficient water to produce 250.0 m!. Mix with the aid of mostly of argon and nitrogen. It is produced from air by the
ultrasound for 5 minutes, shake for 15 minutes and filter. molecular sieve process.
Measure the absorbance of the resulting solution at the
Description. A colourless gas; odourless.
maximum at about 273 nm (2.4.7). Calculate the content of
C,sHz3N03,HCl taking 74.5 as the specific absorbance at Identification
273nm.
A. A glowing splinter of wood bursts into flame on contact
Storage. Store protected from moisture. with the gas.

1835
OXYGEN 93 PER CENT IP 2010

B. Shake with alkaline pyrogallol solution; the gas under Oxytetracycline has a potency not less than 900 flg of
examination is absorbed and the solution becomes dark brown. CzzHz4Nz09, per mg, calculated on the anhydrous basis.
C. When tested as described under Assay, not more than Category. Antibacterial.
10.0 ml and not less than 4.0 ml ofgas remain.
Dose. Orally, 250 to 500 mg every 6 hours; by intramuscular
Tests injection, 1 to 2 g daily.
Description. A tan yellow or light yellow (with or without a
Carbon dioxide. Not more than 300 ppm v/v, determined by
greenish tinge), crystalline powder; odourless.
using a carbon dioxide detector tube (2.1.1).
Carbon monoxide. Not more than 5 ppm v/v, determined by Identification
using a carbon monoxide detector tube (2.1.1).
A. Determine by thin-layer chromatography (2.4.17), coating
Assay (2.3.33). Use 100 ml of the gas under examination and
the plate with the substance prepared by mixing 25 g of silica
place spirals of freshly cleaned copper wire and 125 ml of
gel Gwith 50 ml ofa mixture of2.5 ml ofglycerin and 47.5 ml of
ammonia buffer pH 10.9 in the pipette. The volume of the
0.1 M disodium edetate previously adjusted to pH 7.0 with
residual gas in the burette is not more than 10.0 ml and not
dilute ammonia solution. After spreading the plate, allow it to
less than 4.0 ml.
stand at room temperature till it is dry (70 to 90 minutes).
Storage. Store in cylinders or in a low pressure collecting
tank. Containers used for Oxygen 93 Per Cent must not be Mobile phase. The lower layer formed after shaking 200 ml of
treated with any toxic, sleep-inducing or narcosis-producing a mixture of 2 volumes of ethyl acetate, 2 volumes of
compounds and must not be treated with any compound that chloroform and 1 volume of acetone with 25 ml of 0.1 M
will be irritating to the respiratory tract when the Oxygen disodium edetate previously adjusted to pH 7.0 with dilute
93 Per Cent is used. ammonia solution.

Labelling. Label each outlet "Oxygen 93 Per Cent", when it is Test solution. Dissolve 0.05 g of the substance under
piped directly from the collecting tanle to the point ofuse. Ifit examination in 100 ml of methanol.
is stored in cylinders, reduce the pressure by means ,of a Reference solution (a). A 0.05 per cent w/v solution of
regulator. Measure the gases with a gas volume meter oxytetracycline RS in methanol.
downstream from the detector tube in order to minimise
contamination or change of the specimens. The shOlilder of Reference solution (b). A solution containing 0.05 per cent
the cylinder should be painted white and the remainder should w/v each of demethylchlortetracycline hydrochloride RS,
be painted black. The cylinder should carry a label stating oxytetracycline hydrochloride RS and tetracycline
"Oxygen 93 Per Cent" and "For medicinal use". hydrochloride RS in methanol.
Apply to the plate 1 III of each solution, freshly prepared.
After development, dry the plate in air, expose to the vapours
Oxytetracycline Dihydrate of ammonia and examine in ultraviolet light at 365 urn. The
principal spot in the chromatogram obtained with the test
Oxytetracycline solution corresponds to that in the chromatogram obtained
with reference solution (a). The test is not valid unless the
OH 0 o chromatogram obtained with reference solution (b) shows
three clearly separated spots.
NH z
,2H zG B. To about 0.5 mg add 2 ml of sulphuric acid; a red colour is
produced. Add the solution to 1 ml of water; the colour
changes to yellow.
C. Dissolve about 2 mg in 5 ml of a 1 per cent w/v solution of
sodium carbonate and add 2 ml of diazotised sulphanilic
C:1zHz<tNZC?9,2HzO Mol. Wt. 496.5
acid solution; an orange-red to brownish-red colour is
Oxytetracycline is (4S,4aR,5S,5aR,6S, 12aS)-4-dimethyl produced.
amino-1 ,4,4a,5,5a,6,11,12a-octahydro-3,5,6,10, 12,12a-
hexahydroxy-6-methyl-1,II-dioxonaphthacene-2- Tests
carboxamide dihydrate, a substance produced by the
growth of certain strains of Streptomyces rimosus or obtained pH (2.4.24). 4.5 to 7.5, determined in a 1.0 per cent w/v
by any other means. It contains a variable quantity of water. suspension in freshly boiled and cooled water.

1836
IP 2010 OXYTETRACYCLINE DIHYDRATE

Specific optical rotation (204.22). -203° to -216°, detennined spectrophotometer set at 254 run,
at 20° in a 1.0 per cent w/v solution in 0.1 M hydrochloric injection volume. 20 /ll.
acid, after allowing the solution to stand protected from light
Adjust the sensitivity so that the heights of the peaks in the
for 30 minutes before measurement.
chromatogram obtained with reference solution (d) are at least
Light absorption. Absorbance ofa 0.002 per cent w/v solution 50 per cent of the full-scale deflection of the recorder.
in buffersolution pH2.0 at the maximum at about 353 run, 0.58
The test is not valid unless (a) the resolution between the first
to 0.62 (204.7).
peak (4-epioxytetracycline) and the second peak
Light-absorbing impurities. A. Dissolve 20 mg in sufficient (oxytetracycline) is at least 4.0 (b) the resolution between the
of a mixture of I volume of 1 M hydrochloric acid and second peak and the third peak (tetracycline) is at least 5.0
99 volumes of methanol to produce 10 ml. Absorbance ofthe (the content of 2-methyl-2-propanol in the mobile phase may
resulting solution at about 430 nm, when measured within be adjusted if necessary) and (c) the symmetry factor for the
1 hour ofpreparing the solution, not more than 0.25, calculated second peak is at most 1.25.
on the anhydrous basis (204.7).
Inject reference solution (a) six times. The test is not valid
B. Dissolve 0.1 g in sufficient ofa mixture of 1 volume of 1 M unless the relative standard deviation of the area of the peak
hydrochloric acid and 99 volumes of methanol to produce due to oxytetracycline is not greater than 1.0 per cent.
10 ml. Absorbance ofthe resulting solution at about 490 nm,
Inject the test solution and reference solution (e). In the
when measured within 1 hour of preparing the solution, not
chromatogram obtained with the test solution the area of any
more than 0.20, calculated on the anhydrous basis (204.7).
peak corresponding to 4-epioxytetracycline or tetracycline is
Related substances. Detennine by liquid chromatography not greater than the area of the corresponding peak in the
(204.14). chromatogram obtained with reference solution (e). In the
Test solution. Dissolve 20 mg of the substance under chromatogram obtained with the test solution the area of any
examination in 25 ml of O. DIMhydrochloric acid. peak appearing on the tail of the principal peak is not greater
than 4.0 times that ofthe peak due to 4-epioxytetracycline in
Reference solution (a). Dissolve 20 mg of oxytetracycline RS
the chromatogram obtained with reference solution (e).
in 25 ml of O. DIM hydrochloric acid.
Heavy metals (2.3.13).004 g complies with limit the test for
Reference solution (b). Dissolve 20 mg of 4-epioxytetra-
heavy metals, Method B (50 ppm).
cycline RS in 25 ml of 0.01 M hydrochloric acid.
Sulphated ash (2.3.18). Not more than 0.5 per cent.
Reference solution (c). Dissolve 20 mg of tetracycline
hydrochloride RS in 25 ml of 0.01 M hydrochloric acid. Water (2.3043). 4.0 to 9.0 per cent, detennined on 0.5 g.
Reference solution (d). Dilute a mixture of 1.5 ml ofreference Assay. Detennine by the microbiological assay ofantibiotics,
solution (a), 1.0 ml of reference solution (b) and 3.0 ml of Method A or B (2.2.10), and express the results in /lg of
reference solution (c) to 25 ml with 0.01 M hydrochloric oxytetracycline, CzzHz4Nz09' per mg.
acid. Oxytetracycline intended for use in the manufacture of
Reference solution (e). Dilute a mixture of 1.0 ml ofreference parenteral preparations without a fUrther procedure for the
solution (b) and 4.0 ml.ofreference solution (c) to 200 rn1 with removal ofbacterial endotoxins complies with the jrjl!owing
0.01 M hydrochloric acid. additional requirement.
Chromatographic system Bacterial endotoxins (2.2.3). Not more than 004 Endotoxin Unit
- a stainless steel column 25 cm x 4.6 mm, packed with . per mg ofOxytetracycline.
styrene- divinylbenzene co-polymer (8 to 10 /lm), Oxytetracycline intended for use in the manufacture of
- column temperature. 60°, parenteral preparations without a further sterilisation
- 'mobile phase: add 60 g of 2-methyl-2-propanol to a procedure complies with the following additional
volumetric flask with the aid of 200 ml of water, add requirement.
60 ml of 0.33 M phosphate buffer pH 7.5, 50 ml of a
Sterility. Complies with the test for sterility (2.2.11).
1.0 per cent w/v solution of tetrabutylammonium
hydrogen sulphate previously adjusted to pH 7.5 with Storage. Store protected from light and moisture. If it is
2 M sodium hydroxide and 10 ml of a 0.04 per cent w/v intended for use in the manufacture ofparenteral preparations,
solution of disodium edetate previously adjusted to the container should be sterile and sealed so as to exclude
pH 7.5 with 2 M sodium hydroxide and dilute to micro-organisms.
1000.0 ml with water, .Labelling. The label states whether or not the contents are
- flowrate. 1 ml per minute, intended for use in the manufacture ofparenteral preparations.

1837
OXYTETRACYCLINE INJECTION IP 2010

Oxytetracycline Injection Bacterial endotoxins (2.2.3). Not more than 004 Endotoxin Unit
per mg ofOxytetracycline.
Oxytetracycline Injection is a sterile solution ofoxytetracycline
Other tests. Complies with the tests stated under Parenteral
with or without one or more suitable buffering agents,
Preparations (Injections).
anaesthetics, preservatives, antioxidants, complexing agents
and solvents. Assay. Determine by the microbiological assay ofantibiotics,
Method A or B (2.2.10), and express the result in mg of
Oxytetracycline Injection contains not less than 90.0 per cent
and not more than 120.0 per cent of the stated amount of oxytetracycline, CzzHz4Nz09' per ml.
anhydrous oxytetracycline, CzzHz4Nz09' Storage. Store protected from light.
Usual strengths. 50 mg per ml; 125 mg per ml. Labelling. The label states (1) the strength in mg ofanhydrous
oxytetra,cycline per ml; (2) that the contents are to be used for
Description. A clear, yellow to tan yellow solution. It may
intramuscular use only; (3) the names of any preservatives
have a greenish tinge.
used.
Identification
A. Determine by thin-layer chromatography (204.17), coating Oxytetracycline Hydrochloride
the plate with the substance prepared by mixing 25 g of silica
gel G with 50 ml ofa mixture of2.5 ml ofglycerin and 47.5 ml of Mol. Wt. 496.9
0.1 M disodium edetate previously adjusted to pH 7.0 with Oxytetracycline Hydrochloride is (4S,4aR,5S,5aR,6S, l2a8)-
dilute ammonia solution. After spreading the plate, allow it to 4-dimethylaIDino-l,4,4a,5,5a,6,11,12a-octahydro-3,5,
stand at room temperature till it is dry (70 to 90 minutes). 6,10,12, 12a-hexahydroxy-6-methyl-l ,11-dioxonaphthacene-2-
Mobile phase. The lower layer fonned after shaking 200 ml of carboxamide hydrochloride, a substance produced by
a mixture of 2 volumes of ethyl acetate, 2 volumes of the growth of certain strains of Streptomyces rimosus or
chloroform and 1 volume of acetone with 25 ml of 0.1 M obtainedby any other means.
disodium edetate previously adjusted to pH 7.0 with dilute Category. Antibacterial.
ammonia solution.
Dose. Orally, 250 to 500 mg every 6 hours; by intravenous
Test solution. Shake a quantity containing 10 mg ofanhydrous infusion, in a concentration of 0.1 per cent w/v, 1 to 2 g daily.
oxytetracycline with 20 ml of methanol, centrifuge if necessary
and use the clear supernatant liquid. Description. A pale yellow, crystalline powder; odour1ess;
hygroscopic.
Reference solution (a). A 0.05 per cent w/v solution of
oxytetracycline hydrochloride RS in methanol. Oxytetracycline Hydrochloride has a potency not less than
835 flg of CzzHz4Nz09, per mg, calculated on the anhydrous
Reference solution (b). A solution containing 0.05 per cent basis.
w/v each of demethylchlortetracycline hydrochloride RS,
oxytetracycline hydrochloride RS and tetracycline Identification
hydrochloride RS in methanol.
A. Determine by thin-layer chromatography (204.17), coating
Apply to the plate 1 fll of each solution, freshly prepared. the plate with the substance prepared by mixing 25 g of silica
After development, dry the plate in air, expose to the vapours gel G with 50 ml ofa mixture of2.5 mlofglycerin and 47.5 ml of
of ammonia and examine in ultraviolet light at 365 nm. The 0.1 M disodium edetate previously adjusted to pH 7.0 with
principal spot in the chromatogram obtained with the test dilute ammonia solution. After spreading the plate, allow it to
solution corresponds to that in the chromatogram obtained stand at room temperature till it is dry (70 to 90 minutes).
with reference solution (a). The test is not valid unless the Mobile phase. The lower layer formed after shaking 200 m1 of
chromatogram obtained with reference solution (b) shows a mixture of 2 volumes of ethyl acetate, 2 volumes of
three clearly separated spots.
chloroform and 1 volume of acetone with 25 m1 of 0.1 M
B. Add 0.1 ml to 2 ml ofsulphuric acid; a red colour is produced. disodium edetate previously adjusted to pH 7.0 with dilute
Add the solution to 1 ml of water; the colour changes to ammonia solution.
yellow. Test solution. Dissolve 0.05 g of the substance under
examination in 100 ml of methanol.
Tests
Reference solution (a). A 0.05 per cent w/v solution of
pH (204.24). 8.0 to 9.0. oxytetracycline hydrochloride RS in methanol.

1838
IP 2010 OXYTETRACYCLINE HYDROCHLORlDE

Reference solution (b). A solution containing 0.05 per cent Reference solution (c). Dissolve 20 mg of tetracycline
w/v each of demethylchlortetracycline hydrochloride RS, hydrochloride RS in 25 ml of 0.01 M hydrochloric acid.
oxytetracycline hydrochloride RS and tetracycline
Reference solution (d). Dissolve 20 mg of a..-apo-
hydrochloride RS in methanol.
oxytetracycline RS in 20 ml of 0.01 M sodium hydroxide and
Apply to the plate 1 J!l of each solution, freshly prepared. dilute to 250 ml with 0.01 M hydrochloric acid.
After development, dry the plate in air, expose to the vapours
Reference solution (e). Dissolve 20 mg of ~ -apo-
of ammonia and examine in ultraviolet light at 365 nm. The
oxytetracycline RS in 20 ml of 0.01 M sodium hydroxide and
principal spot in the chromatogram obtained with the test
dilute to 250 ml with 0.01 M hydrochloric acid.
solution corresponds to that in the chromatogram obtained
with reference solution (a). The test is not valid unless the Reference solution (f), Dilute a mixture of 1.5 ml ofreference
chromatogram obtained with reference solution (b) shows solution (a), 1.0 ml of reference solution (b), 3.0 ml each of
three clearly separated spots. reference solutions (c) (d) and (e) to 25 ml with 0.01 M
hydrochloric acid.
B. To about 0.5 mg add 2 ml of sulphuric acid; a red colour is
produced. Add the solution to 1 ml of water; the colour Reference solution (g). Dilute a mixture of 1.0 ml ofreference
changes to yellow. solution (b), 4.0 ml of reference solution (c) and 40.0 ml of
reference solution (e) to 200 ml with 0.01 M hydrochloric
C. Dissolve about 2 mg in 5 ml of a 1 per cent w/v solution of
acid.
sodium carbonate and add 2 ml of diazotised sulphanilic
acid solution; an orange-red to brownish-red colour is Chromatographic system
produced. - a stainless steel column 25 cm x 4.6 mm, packed with
styrene-divinylbenzene co-polymer (8 to 10 J!m),
D. A 5 per cent w/v solution gives the reactions of chlorides
- column temperature. 60°,
(2.3.1).
- mobile phase: transfer separately 30 g (for mobile phase
Tests A) orl 00 g (for mobile phase B) of 2-methyl-2-propanol
to volumetric flasks with the aid of200 ml of water; to
pH (2.4.24).2.0 to 3.0, determined in a 1.0 per cent w/v solution. each flask add 60 ml of 0.33 M phosphate buffei'pH 7.5,
Specific optical rotation (2.4.22). -188° to -200°, determined 50 ml of a 1.0 per cent w/v solution of tetrabutyl-
at 20° in a 1 per cent w/v solution in 0.1 M hydrochloric acid. ammonium hydrogen sulphate previously adjusted to
pH 7.5 with 2 M sodium hydroxide and 10 ml of a 0.04
Light absorption (2.4.7). Absorbance ofa 0.002 per cent w/v
per cent w/v solution of disodium edetate previously
solution in chloride buffer solution pH 2.0 at the maximum at
adjusted to pH 7.5 with 2 M sodium hydroxide and
about 353 nm, 0.54 to 0.58.
dilute each solution to 1000.0 ml with water.,
Light-absorbing impurities. A. Dissolve 20 mg in sufficient flow rate. 1 ml per minute,
of a mixture of 1 volume of 1 M hydrochloric acid and - spectrophotometer set at 254 nm,
99 volumes of methanol to produce 10 ml. Absorbance ofthe - injection volume. 20 J!l.
resulting solution at about 430 urn, when measured within
Carry out a one-step gradient elution in the following manner.
1 hour ofpreparing the solution, not more than 0.50, calculated
Pump a mixture containing 30 volumes ofmobile phase Band
on the anhydrous basis (2.4.7).
70 volumes of mobile phase A for 15 minutes, then pump a
B. Dissolve 0.1 g in sufficient ofa mixture of 1 volume of 1 M mixture containing 30 volumes of mobile phase A and
hydrochloric acid and 99 volumes of methanol to produce 70 volumes of mobile phase B for 15 minutes and finally
10 ml. Absorbance of the resulting solution at about 490 nm, equilibrate with the first mixture. Adjust the sensitivity so that
when measured within 1 hour of preparing the solution, not the heights of the peaks in the chromatogram obtained with
more than 0.20, calculated on the anhydrous basis (2.4.7). reference solution (f) are at least 50 per cent of full-scale
deflection ofthe recorder.
Related substances. Determine by liquid chromatography
(2.4.14). The test is not valid unless, in the chromi;ltogram obtained
with reference solution (f), (a) the resolution between the first
Test solution. Dissolve 20 mg of the substance under
peak (4-epioxytetracycline) and the second peak
examination in 25 ml of O. 01 M hydrochloric acid.
(oxytetracycline) is at least 4.0, (b) the resolution between the
Reference solution (a). Dissolve 20 mg of oxytetracycline RS second peak and the third peak (tetracycline) is at least 5.0, (c)
in 25 ml of O. 01 M hydrochloric acid. the resolution between the fourth peak (a..-apo-
Reference solution (b). Dissolve 20 mg of 4-epioxytetra- oxytetracycline) and the fifth peak (~-apo-oxytetracycline)
cycline RS in 25 ml of 0.01 M hydrochloric acid. is at least 3.5, and (d) the symmetry factor ofthe second peak

1839
OXYTETRACYCLINE HYDROCHLORIDE IP 2010

is at most 1.25. If necessary adjust the proportions of the Oxytetracycline Capsules


mobile phases used to produce the one-step gradient elution.
Adjust the time-programme for the one-step gradient elution Oxytetracycline Hydrochloride Capsules
if necessary.
Oxytetracycline Capsules contain not less than 95.0 per cent
Inject reference solution (a) six times. The test is not valid if and not more than 110.0 per cent of the stated amount of
the relative standard deviation of the area of the peak due to oxytetracycline hydrochloride, CzzHz4Nz09,HCl.
oxytetracycline is greater than 1.0 per cent. Ifnecessary, adjust
Usual strengths. 250 mg; 500 mg.
the integrator parameters.
Inject the test solution and reference solution (g). In the Identification
chromatogram obtained with the test solution the area of any
peak corresponding to 4-epioxytetracycline or tetracycline A. Determine by thin-layer chromatography (204.17), coating
is not greater than the area of the corresponding peak in the the plate with the substance prepared by mixing 25 g of
chromatogram obtained with reference solution (g) and the silica gel G with 50 ml of a mixture of 2.5 ml of glycerin and
total area ofthe peaks corresponding to a-apo-oxytetracycline 47.5 ml of 0.1 M disodium edetate previously adjusted to pH
and to ~ -apo-oxytetracycline and any peak between the latter 7.0 with dilute ammonia solution. After spreading the plate,
two is not greater than the area of the peak due to ~ -apo- allow it to stand at room temperature till it is dry (70 to 90
oxytetracycline in the chromatogram obtained with reference minutes).
solution (g). In the chromatogram obtained with the test
Mobile phase. The lower layer formed after shaking 200 ml of
solution the area of any peak appearing on the tail of the
a mixture of 2 volumes of ethyl acetate, 2 volumes of
principal peak is not greater than 4.0 times that ofthe peak due
chloroform and 1 volume of acetone with 25 ml of 0.1 M
to 4-epioxytetracycline in the chromatogram obtained with
disodium edetate previously adjusted to pH 7.0 with dilute
reference solution (g).
ammonia solution.
Heavy metals (2.3.13).004 g complies with the limit test for
Test solution. Extract a quantity ofthe contents ofthe capsules
heavy metals, Method B (50 ppm).
containing 10 mg ofOxytetracycline Hydrochloride with 20 ml
Sulphated ash (2.3.18). Not more than 0.5 per cent. methanol, centrifuge and use the supernatant liquid.
Water (2.3043). Not more than 2.0 per cent w/w, determined on Reference solution (a). A 0.05 per cent w/v solution of
0.5 g. oxytetracycline hydrochloride RS in methanol.
Assay. Determine by the microbiological assay ofantibiotics, Reference solution (b). A solution containing 0.05 per cent
Method A or B (2.2.10), and express the result in Ilg of w/v each of demethylchlortetracycline hydrochloride RS,
oxytetracycline, CzzHz4Nz09, per mg. oxytetracycline hydrochloride RS and tetracycline
hydrochloride RS in methanol.
Oxytetracycline Hydrochloride intended for use in the
manufacture ofparenteral preparations without a fitrther Apply to the plate 1 III of each solution, freshly prepared.
procedure for the removal ofbacterial endotoxins complies After development, dry the plate in air, expose to the vapours
with the following additional requirement. of ammonia and examine in ultraviolet light at 365 nm. The
principal spot in the chromatogram obtained with the test
Bacterial endotoxins (2.2.3). Not more than 004 Endotoxin Unit
solution corresponds to that in the chromatogram obtained
per mg.
with reference solution (a). The test is not valid unless the
Oxytetracycline Hydrochloride intended for use in the chromatogram obtained with reference solution (b) shows
.manufacture ofparenteral preparations without a jitrther three clearly separated spots.
sterilisation procedure complies with the following
B. To 0.5 mg of the contents of the capsules add 2 ml of
additional requirement.
sulphuric acid; a red colour is produced. Add the solution to
Sterility. Complies with test for sterility (2.2.11). 1 ml of water; the colour changes to yellow.
Storage. Store protected from light and moisture. If it is C. Dissolve about 2 mg ofthe contents ofthe capsules in 5 ml
intended for use in the manufacture ofparenteral preparations, ofa 1 per cent w/v solution of sodium carbonate and add 2 ml
the container should be sterile and sealed so as to exclude of diazotised sulphanilic acid solution; a light brown colour
micro-organisms. is produced.
Labelling. The label states whether or not the contents are D. The contents ofthe capsules give the reactions ofchlorides
intended for use in the manufacture ofparenteral preparations. (2.3.1).

1840
IP 2010 OXYTETRACYLINE EYE OINTMENT

Tests Identification
Light-absorbing impurities. Dissolve a portion ofthe mixed Determine by thin-layer chromatography (2.4.17), coating the
contents of five capsules as completely as possible in plate with the substance prepared by mixing 25 g of silica gel
sufficient of a mixture of 1 volume of 1 M hydrochloric acid G with 50 ml of a mixttLre of2.5 ml ofglycerin and 47.5 ml of
and 99 volumes of methanol to produce two solutions of 0.1 M disodium edetate previously adjusted to pH 7.0 with
Oxytetracycline Hydrochloride containing (1) 0.2 per cent w/v dilute ammonia solution. After spreading the plate, allow it to
and (2) 1.0 per cent w/v and filter each solution. Absorbance stand at room temperature till it is dry (70 to 90 minutes).
ofthe filtrate obtained from solution (1) at about 430 om, when Mobile phase. The lower layer formed after shaldng 200 ml of
measured within 1 hour of preparing the solution, not greater a mixture of 2 volumes of ethyl acetate, 2 volumes of
than 0.75 and ofthe filtrate obtained from solution (2) at about chloroform and 1 volume of acetone with 25 ml of 0.1 M
490 om, not more than 0.40 (2.4.7). disodium edetate previously adjusted to pH 7.0 with dilute
ammonia solution.
Dissolution (2.5.2).
Test solution. A solution prepared by heating a quantity
Apparatus No.1,
containing 20 mg ofOxytetracycline Hydrochloride with 20 ml
Medium. 900 ml of 0.1 M hydrochloric acid,
of methanol for 20 minutes, cooling in ice, filtering, carefully
Speed and time. 100 rpm and 45 minutes. evaporating the filtrate to dryness and dissolving the residue
Withdraw a suitable volume ofthe medium and filter through in 20 ml of methanol.
a membrane filter disc with an average pore diameter not greater Reference solution (a). A 0.05 per cent w/v solution of
than 1.0 j.Lm. Measure the absorbance of the filtrate, suitably oxytetracycline hydrochloride RS in methanol.
diluted ifnecessary, at the maximum at about 353 nm (2.4.7).
Reference solution (b). A solution containing 0.05 per cent
Calculate the content ofCzzH24N209,HCI in the medium taldng
w/v each of demethylchlortetracycline hydrochloride RS,
282 as the specific absorbance at 353 om.
oxytetracycline hydrochloride RS and tetracycline
D. Not less than 75 per cent of the stated amount of hydrochloride RS in methanol.
CnH2~209,HCl.
Apply to the plate 1 j.LI of each solution, freshly prepared.
Loss on drying (2.4.19). Not more than 5.0 percent, determined After development, dry the plate in air, expose to the vapours
on 1.0 g ofthe mixed contents ofthe capsules by drying in an of ammonia and examine in ultraviolet light at 365 nm. The
oven at 60° at a pressure not exceeding 0.7 kPa for 3 hours. principal spot in the chromatogram obtained with the test
solution corresponds to that in the chromatogram obtained
Other tests. Comply with the tests stated under Capsules.
with reference solution (a). The test is not valid unless the
Assay. Weigh accurately a quantity of the mixed contents of chromatogram obtained with reference solution (b) shows
20 capsules containing about 0.25 g of Oxytetracycline three clearly separated spots.
Hydrochloride, add 250.0 ml of water, shake, filter.
Tests
Determine by the microbiological assay ofantibiotics, Method
A or B (2.2.10), and express the results in mg ofoxytetracycline Water (2.3.43). Not more than 1.0 percent, determined on 0.5 g.
hydrochloride per capsule taking each mg of oxytetracycline Other tests. Complies with the tests stated under Eye
to be equivalent to 1.079 mg ofoxytetracycline hydrochloride, Ointments.
CnH2~209,HCl. Assay. Weigh accurately about 1.0 g and transfer to a
Storage. Store protected from light and moisture. separating funnel. Add 25 ml of peroxide-free ether, shake
well and extract with five quantities, each of20 ml, of 0.1 M
hydrochloric acid. Combine the extracts and dilute to
200.0 ml with 0.1 Mhydrochloric acid. Dilute a suitable volume
of the resulting solution with buffer solution No 3 (2.2.10), to
Oxytetracycline Eye Ointment produce a solution containing 1 j.Lg of oxytetracycline per mI.

Oxytetracycline Hydrochloride Eye Ointment Determine by the microbiological assay ofantibiotics, Method
B (2.2.10), and express the results as a percentage of
Oxytetracycline Eye Ointment contains not less than 90.0 per oxytetracycline hydrochloride taking each mg of
cent and not more than 115.0 per cent of the stated amount of oxytetracycline to be equivalent to 1.079 mg ofoxytetracycline
oxytetracycline hydrochloride, CZ2H24N209,HCI. hydrochloride, C22H24Nz09,HCl.
Usual strength. 1 per cent w/w. Storage. Store protected from light and moisture.

1841
OXYTETRACYCLINE HYDROCHLORIDE INJECTION IP 2010

Oxytetracycline Hydrochloride principal spot in the chromatogram obtained with the test
solution corresponds to that in the chromatogram obtained
Injection with reference solution (a). The test is not valid unless the
Oxytetracycline Hydrochloride Injection is a sterile material chromatogram obtained with reference solution (b) shows
consisting of Oxytetracycline Hydrochloride with or without three clearly separated spots.
buffering agents and other excipients. It is filled in a sealed B. To about 0.5 mg add 2 ml of sulphuric acid; a red colour is
container. produced. Add the solution to I ml of water; the colour
The injection is constituted by dissolving the contents ofthe changes to yellow.
sealed container in the requisite amount of sterile Water for C. Dissolve about 2 mg in 5 ml of a I per cent w/v solution of
Injections, immediately before use. sodium carbonate and add 2 ml of diazotised sulphanilic
The constituted solution complies with the requirements for acid solution; an orange-red to brownish-red colour is
Clarity of solution and Particulate matter stated under produced.
Parenteral Preparations (Injections).
Tests
Storage. The constituted solution may be used within three
days of preparation when stored in a refrigerator (20 to 8°). Appearance of solution. A 10.0 per centw/v solution is clear
(2.4.1) and yellow.
Oxytetracycline Hydrochloride Injection contains not less than
pH (2.4.24). 2.0 to 3.0, determined in a 1.0 per cent w/v solution.
90.0 per cent and not more than 115.0 per cent of the stated
amount ofoxytetracycline, CzzHz4NzOg. Light-absorbing impurities. A. Dissolve 20 mg in sufficient
of a mixture of I volume of 1 M hydrochloric acid and
The contents of the sealed container comply with the
99 volumes of methanol to produce 10 ml. Absorbance ofthe
requirements stated under Parenteral Preparations
resulting solution at about 430 nm, when measured within
(Powdersfor Injection) and with thefollowing requirements.
I hour ofpreparing the solution, not more than 0.50, calculated
Usual strengths. The equivalent of 250 mg and 500 mg of on the anhydrous basis (2.4.7).
oxytetracycline.
B. Dissolve 0.1 g in sufficient ofa mixture of I volume of 1 M
Description. A pale yellow, crystalline powder. hydrochloric acid and 99 volumes of methanol to produce
10 ml. Absorbance of the resulting solution at about 490 nm,
Identification when measured within 1 hour of preparing the solution, not
A. Determine by thin-layer chromatography (2.4.17), coating more than 0.20, calculated on the anhydrous basis (2.4.7).
the plate with the substance prepared by mixing 25 g of silica Assay. Determine by the microbiological assay ofantibiotics,
gel G with 50 ml ofa mixture of2.5 ml ofglycerin and 47.5 m1 of method A or B (2.2.10), and express the result in )..I.g of
0.1 M disodium edetate previously adjusted to pH 7.0 with oxytetracycline, CzzHz4NzOg, per mg.
dilute ammonia solution. After spreading the plate, allow it to
Bacterial endotoxins (2.2.3). Not more than 0.4 Endotoxin Unit
stand at room temperature till it is dry (70 to 90 minutes).
per mg.
Mobile phase. The lower layer formed after shaking 200 ml of
Storage. Store protected from light and moisture.
a mixture of 2 volumes of ethyl acetate, 2 volumes of
chloroform and I volume of acetone with 25 ml of 0.1 M Labelling. The label states (I) the quantity ofOxytetracycline
disodium edetate previously adjusted to pH 7.0 with dilute Hydrochloride contained in it in terms of the equivalent
ammonia solution. amount of oxytetracycline; (2) that the contents are to be
used for intravenous injection only; (3) the names of the
Test solution. Dissolve 0.05 g of the substance under buffering agents used.
examination in 100 m1 of methanol.
Reference solution (a). A 0.05 per cent w/v solution of
oxytetracycline hydrochloride RS in methanol.
Oxytocin
Reference solution (b). A solution containing 0.05 per cent
w/v each of demethylchlortetracycline hydrochloride RS, Cys-Tyr-lle-Gln-Asn-Cys-Pro-Leu-GlyNH z
oxytetracycline hydrochloride RS and tetracycline
hydrochloride RS in methanol.
I I
Apply to the plate I )..1.1 of each solution, freshly prepared. Mol. Wt.1007.2
After development, dry the plate in air, expose to the vapours Oxytocin is a cyclic nonapeptide hormone obtained by a
of ammonia and examine in ultraviolet light at 365 nm. The process offractionation from the posterior lobe ofthe pituitary

1842
IP 2010 OXYTOCIN

gland of healthy oxen or other mammals or by synthesis that containing the dried samples in a vessel that contains an
has the property of stimulating contraction of the uterus and appropriate amount of hydrolysis solution. The hydrolysis
mille ejection in receptive animals. It may be presented as a solution does not come in contact with the test sample. Apply
solid or as a solution in a solvent containing an appropriate an inert atmosphere or vacuum (less than 200 fl.m ofmercury
antimicrobial preservative such as 0.2 per cent w/v solution of or 26.7 Pa) to the headspace of the vessel, and heat to about
chlorbutol. 110° for a 24 hours hydrolysis time. Acid vapour hydrolysis
the dried sample. Any condensation ofthe acid in the sample
Ifit is derived from animal species, Oxytocin contains not less
vials is to be minimised. After hydrolysis, dry the test sample
than 95.0 percent and not more than 105.0 per cent of the
in vacuum to remove any residual acid.
stated number of Units of oxytocic activity. If it is a synthetic
product presented as a solid, it contains not less than 560 For analysis-Past-column ninhydrin derivatisation. Ion-
Units per mg, calculated with reference to the peptide content exchange chromatography with post-column ninhydrin
and when presented as a liquid, it contains not less than 150 derivatisation is one ofthe most common methods employed
Units per ml. for quantitative amino acid analysis. As a rule, a lithium-based
Category. Oxytocic. cation-exchange system is employed for the analysis of the
more complex physiological samples, and the faster sodium-
Description. When presented as a solid, a white or almost based cation-exchange system is used for the more simplistic
white powder. When presented as a liquid, a clear colourless amino acid mixtures obtained with protein hydrolysates
liquid. (typically containing 17 amino acid components). Separation
ofthe amino acids on an ion-exchange column is accomplished
Identification
through a combination of changes in pH and cation strength.
Test B may be omitted if tests A and C are carried out. Test C A temperature gradient is often employed to enhance
may be omitted if tests A and B are carried out. separation.

A. In the Assay, the principal peak in the chromatogram When the amino acid reacts with ninhydrin, the reactant has a
obtained with the test solution corresponds to the peak in the characteristic purple or yellow colour. Amino acids, except
chromatogram obtained with the reference solution. imino acid, give a purple colour, and show an absorption
maximum at 570 nm. The imino acids such as proline give a
B. Amino acid analysis.
yellow colour, and show an absorption maximum at 440 urn.
For hydrolysis-Acid hydrolysis using hydrochloric acid The post-column reaction between ninhydrin and amino acids
containing phenol is the most common procedure used for eluted from the column is monitored at 440 nm and 570 urn,
protein/peptide hydrolysis preceding amino acid analysis. The and the chromatogram obtained is used for the determination
addition of phenol to the reaction prevents the halogenation of amino acid composition.
of tyrosine.
The detection limit is considered to be 10 pmol for most ofthe
Hydrolysis solution. 6 M hydrochloric acid containing 0.1 amino acid derivatives, but 50 pmol for the proline derivative.
per cent to 1.0 per cent of phenol. Response linearity is obtained in the range of 20-500 pmol
with con-elation coefficients exceeding 0.999. To obtain good
Procedure
composition data, samples larger than 1 fl.g before hydrolysis
Liquidphase hydrolysis. Place the protein or peptide sample are best suited for this amino acid analysis ofprotein/peptide.
in a hydrolysis tube, and dry (the sample is dried so that water
Express the content ofeach amino acid in moles. Calculate the
in the sample will not dilute the acid used for the hydrolysis).
relative proportions of the amino acids, taking 1/6 of the sum
Add 200 fl.l of hydrolysis solution per 500fl.g oflyophilised
ofthe number ofmoles ofaspartic acid, glutamic acid, proline,
protein. Freeze the sample tube in a dry ice-acetone bath, and
glycine, isoleucine and leucine as equal to 1.
flame seal in vacuum. Samples are typically hydrolysed at
110° for 24 hours in vacuum or in an inert atmosphere to The values fall within the following limits: aspartic acid: 0.90
prevent oxidation. Longer hydrolysis times (e.g. 48 hours and to 1.10; glutamic acid: 0.90 to 1.10; proline: 0.90 to 1.10; glycine:
72 hours) are investigated ifthere is a concern that the protein 0.90 to I.I 0; leucine: 0.90 to I.I 0; isoleucine: 0.90 to I.I 0;
is not completely hydrolysed. tyrosine: 0.7 to 1.05; half-cystine: 1.4 to 2.1. Not more than
traces of other amino acids are present.
Vapour phase hydrolysis. This is one of the most common
acid hydrolysis procedures, and it is preferred for microanalysis C. For biological response, dissect out the uterus from a virgin
when only small amounts of the sample are available. female rat weighing between 120 to 200 g and in diestrus stage.
Contamination of the sample from, the acid reagent is also Immediately before injection confirm the uterine stage ofthe
minimised by using vapour phase hydrolysis. Place vials rat by vaginal smear. Suspend one hom of the uterus in a

1843
OXYTOXIN IP 2010

organ bath containing 9.0 g of sodium chloride, 0.42 g of mobile phase: appropriate proportions ofa 1.56 per cent
potassium chloride, 0.16 g of calcium chloride, 0.50 g of w/v solution of sodium dihydrogen phosphate (mobile
sodium bicarbonate, 0.25 g of dextrose, and 0.0053 g of phase A) and a mixture ofequal volumes of acetonitrile
magnesium chloride per litre of the solution. Maintain the and water (mobile phase B),
bath temperature at 32° or any other suitable temperature at flow rate. 1 ml per minute,
which spontaneous contractions of the uterus are abolished spectrophotometer set at 220 urn,
and the preparations maintain its sensitivity. Oxygenate the injection volume: 20 /ll
bath solution with a mixture of 95 per cent oxygen and 5 per Equilibrate the column with a mixture of 70 volumes ofmobile
cent carbon dioxide. Record the contractions of the uterine phase A and 30 volumes of mobile phase B and record the
muscle on a recorder, using a suitable instrument producing chromatograms as follows. Operate by gradient elution
linear response (for example an isotonic liver with a load of increasing continuously and linearly the proportion ofmobile
not exceeding 2 g or isotonic and linear transducer). Add to phase B by 1.0 per cent v/v per minute for 30 minutes. Finally
the bath two appropriate dilutions of the oxytocin reference elute using the same mixture for 15 minutes to re-equilibrate
solution, and record the contraction of the muscle following the column.
each dilution. The appropriate dilutions (doses) are those
dilutions of the reference solution which produce clearly Calculate the content ofthe peptide, C43H66NIZ0IZSZ.
distinctive submaximal contractions. The required dilution Assay. Determine by liquid chromatography (2.4.14).
normally lies between 0.1 to 5 micro units per ml of the bath Test solution. Dissolve about 25 mg of the substance under
solution. When maximal contraction is reached, replace the examination in 100 ml ofmobile phase A.
bath solution by a fresh solution and wait until the muscle is
relaxed completely and the pointer of the recorder returns to Reference solution. A 0.025 per cent w/v solution of oxytocin
the base line. The doses of the different reference solutions RS in mobile phase A.
should be added at regular intervals depending upon the rate Chromatographic system
of the recovery of the uterine muscle. Dissolve or dilute the a stainless steel column 12.5 cm x 4.6 mm, packed with
preparation to be tested in a suitable diluent (preferably using octadecylsilane bonded to porous silica (5 /lm),
bath solution) to obtain responses on the addition of two mobile phase: A. a 1.6 per cent w/v solution of sodium
dilutions similar to the one used with the oxytocin reference dihydrogen phosphate,
solution. The two selected dilutions ofthe reference solution B. a mixture of 50 volumes of acetonitrile
and preparation under examination should be applied and 50 volumes of water,
according to a randomised block or Latin square design and a linear gradient programme using the conditions given
at least three responses to each dilution should be recorded. below,
The magnitude of contractions obtained with the reference flow rate. 1 ml per minute,
solution is comparable to the contractions obtained with the spectrophotometer set at 220 urn,
test solution. injection volume. 25 Ill.
Time Mobile phase A Mobile phase B
Tests (in min) (per cent v/v) (per cent v/v)
0-30 70-740 30-760
Peptide. 90.0 to 11 0.0 per cent ofthe stated amount ofoxytocin,
C43H66NIZ0IZSZ expressed per mg for the solid, and in mg per 30-30.1 40-770 60-730
ml for the liquid, 30.1- 45 70 30
Determine by liquid chromatography (2.4.14). Inject the test solution and the reference solution.

Test solution. Dissolve 3.5 mg of the substance under Calculate the content OfC43H66N120IzSz.
examination in sufficient of a 1.56 per cent w/v solution of Oxytocin intended for use in the manufacture ofparenteral
sodium dihydrogen phosphate to produce 10.0 ml or use the preparations without a fUrther procedure for the removal of
liquid preparation as appropriate. bacterial endotoxins complies with the following additional
Reference solution. Dissolve 3.5 mg ofoxytocin RS in sufficient requirement.
of a 1.56 per cent w/v solution of sodium dihydrogen Bacterial endotoxins (2.2.3). Less than 0.5 Endotoxin Units
phosphate to produce 10.0 ml. per Unit ofoxytocin.
Chromatographic system Oxytocin intended for use in the manufacture ofparenteral
a stainless steel column 12 cm x 4.6 mm, packed with preparations without a further sterilisation procedure
octadecylsilane bonded to porous silica (5 /lm), complies with the following additional requirement.

1844
IP 20ID OXYTOCIN INJECTION

Sterility (2.2.11). Complies with the test for sterility. - mobile phase: a mixture of85 volumes ofa 0.2 per cent
Storage. Store protected from moisture. If the substance is v/v solution of orthophosphoric acid and 15 volumes
intended for use in the manufacture ofparenteral preparations, of acetonitrile,
the container should be sterile, tamper-evident and sealed so flow rate. 1 ml per minute,
as to exclude micro-organisms. spectrophotometer set at 220 nm,
- injection volume. 200 J.Ll.
Labelling. The label states (1) the number ofUnits ofoxytocic
activity per mg (for solid) or per ml (for liquid); (2) either the Inject the reference solution. The test is not valid unless the
animal species from which it is obtained or whether it is theoretical plates are not less than 50,000.
synthetic, as appropriate; (3) whether or not the contents are Inject the test solution and the reference solution.
intended for use in the manufacture ofparenteral preparations.
Calculate the content ofC43H66NlzOlzSz in the injection.
Oxytocin Injection containing Oxytocin of natural origin
obtained by extraction and purification complies with the
follOWing additional requirement.
Oxytocin Injection
Vasopressin impurity. Not more than 0.5 Unit perml.
Oxytocin Injection is a sterile solution of Oxytocin in Water
for Injections. Determine by liquid chromatography (2.4.14).

Oxytocin Injection contains not less than 95.0 per cent and Solvent mixture. Dissolve 5.0 g of chlorobutanol in 5.0 ml of
not more than 105.0 per cent ofthe stated number ofUnits of glacial acetic acid, add 1.1 g of sodium acetate, 5.0 g of
oxytocin activity. ethanol, and dilute to 1000 ml with water and mix.

Usual strengths. 5 Units per ml; 10 Units per ml. Test solution. Dilute 2.0 ml of injection under examination to
25 ml with 0.25 per cent w/v of glacial acetic acid and mix.
Description. A clear colourless liquid.
Reference solution. Dissolve the contents of one vial of
Identification vasopressin RS in a lmown volume of solvent mixture. If
necessary dilute the prepared solution to a working
In the Assay, the principal peak in the chromatogram obtained concentration range.
with the test solution corresponds to the peak in the
chromatogram obtained with the reference solution. Chromatographic system
a stainless steel column 25 cm x 4.6 mm, packed with
Tests endcapped octadecylsilane bonded to porous silica
(5 J.Lm),
pH(2.4.24).3.0t05.0 column temperature. 30°,
mobile phase: a mixture of 87 volumes of 6.6 per cent
Bacterial endotoxins (2.2.3). Less than 0.5 Endotoxin Units
v/v solution of dibasic ammonium phosphate, adjusted
per Unit ofoxytocin.
to pH 3.0 with orthophosphoric acid and 13 volumes of
Other tests. Complies with the tests stated under Parenteral acetonitrile, filter through 0.45 J.Lm nylon membrane,
Preparations (Injections). flow rate. 1 ml per minute,
spectrophometer set at 220 nm,
Assay. Determine by liquid chromatography (2.4.14).
- injection volume. 20 J.L1.
Test solution. Use the injection under examination.
Equilibrate the column at least for one hour. Run the
Reference solution. Dissolve the contents of one vial of chromatogram minimum of60 minutes.
oxytocin RS in a 1.65 per cent w/v solution of sodium
Inject the reference solution. The test is not valid unless the
dihydrogen orthophosphate to produce a solution containing
resolution between vasopressin and the adjacent peak is not
the same concentration in J.Lg of oxytocin as that stated on the
less than 1.5 and relative standard deviation for replicate
label ofthe injection.
injections is not more than 2.0 per cent.
Chromatographic system
Inject the reference solution and the test solution.
a stainless steel column 10 cm x 4.6 mm, packed with
endcapped octadecylsilane bonded to porous silica (5 Labelling. The label states (1) the number ofUnits ofoxytocin
J.Lm) (such as Nucleosil C18), activity per ml; (2) either the animal spieces from which it is
column temperature. 40°, obtained or whether it is synthetic, as appropriate.

1845
OXYTOXIN NASAL SOLUTION IF 2010

Oxytocin Nasal Solution Calculate the content ofC43H66NlzOlzSzin the nasal solution.
Oxytocin Nasal Solution containing Oxytocin of natured
Oxytocin Nasal Solution is a solution ofOxytocin in a suitable
origin obtained by extraction and purification complies with
solvent containing an appropriate antimicrobial preservative.
the follOWing additional requirement.
Oxytocin Nasal Solution contains not less than 85.0 per cent
Vasopressin impurity. Not more than 0.5 Unit perml.
and not more than 120.0 per cent ofthe stated number ofUnits
ofoxytocic activity. Detennine by liquid chromatography (2.4.14).
Usual streugth. 40 Units perml. Solvent mixture. Dissolve 5.0 g of chlorobutanol in 5.0 ml of
Description. A clear, colourless solution. glacial acetic acid, add 1.1 g of sodium acetate, 5.0 g of
ethanol, and dilute to 1000 ml with water and mix.
Identification Test solution. Dilute 2.0 ml of injection under examination to
25 ml with 0.25 per cent w/v of glacial acetic acid and mix.
In the Assay, the principal peak in the chromatogram obtained
with the test solution corresponds to the peak in the Reference solution. Dissolve the contents of one vial of
chromatogram obtained with the reference solution. vasopressin RS in a known volume of solvent mixture. If
necessary dilute the prepared solution to a working
Tests concentration range.
pH (2.4.24). 3.0 to 5.0 Chromatographic system
Other tests. Complies with the tests stated under Nasal a stainless steel column 25 cm x 4.6 mm, packed with
Preparations. endcapped octadecylsilane bonded to porous silica (5
/lIn),
Assay. Detennine by liquid chromatography (2.4.14). column temperature. 30°,
Test solution. Use the nasal solution under examination. mobile phase: a mixture of87 volumes of6.6per cent vi
v solution of dibasic ammonium phosphate, adjusted
Reference solution. Dissolve the contents of one vial of
to pH 3.0 with orthophosphoric acid and 13 volumes of
oxytocin RS in a 1.65 per cent w/v solution of sodium
acetonitrile, filter through 0.45 f-lm nylon membrane,
dihydrogen orthophosphate to produce a solution containing
flow rate. 1 ml per minute,
the same concentration in f-lg ofoxytocin as that stated on the
spectrophometer set at 220 urn,
label of the nasal solution.
injection volume. 20 f-ll.
Chromatographic system
a stainless steel column 10 cm x 4.6 mm, packed with Equilibrate the column at least for one hour. Run the
endcapped octadecylsilane bonded to porous silica (5 chromatogram minimum of60 minutes.
f-lm) (such as Nucleosil CI8), Inject the reference solution. The test is not valid unless the
column temperature. 40°, resolution between vasopressin and the adjacent peak is not
mobile phase: a mixture of85 volumes ofa 0.2 per cent less than 1.5 and relative standard deviation for replicate
v/v solution of orthophosphoric acid and 15 volumes injections is not more than 2.0 per cent.
of acetonitrile,
- flow rate. 1 ml per minute, Inject the reference solution and the test solution.
- spectrophotometer set at 220 nm, Storage. Store at a temperature not exceeding 30°.
- injection volume. 200 f-ll.
Labelling. The label states (1) the number ofUnits ofoxytocic
Inject the reference solution. The test is not valid unless the activity per ml; (2) either the animal species from which it is
theoretical plates is not less than 50,000. obtained or whether it is synthetic, as appropriate; (3) that the
Inject the test solution and the reference solution. preparation is intended for intranasal administration only.

1846
INDIAN PHARMACOPOEIA 2010 MONOGRAPHS

Paclitaxel 1853
Paclitaxel fujection 1854
Pancreatin 1855
D-Panthenol 1856
Pantoprazole Sodium 1856
Pantoprazole Sustained-release Tablets 1857
Paracetamol 1859
Paracetamol Syrup 1860
Paracetamol Tablets 1861
Hard Paraffin 1862
Liquid Paraffin . 1862
Light Liquid Paraffin 1863
Liquid ParaffinEmulsion 1863
White SoftParaffin 1863
Yellow SoftParaffin 1864
Paraffin Ointment 1865
Paraldehyde 1865
Penicillamine 1866
Penicillamine Tablets 1868
Diluted Pentaerythritol Tetranitrate 18~68

Pentaerythritol Tetranitrate Tablets 1870


Pentamidine Isethionate 1871
Pentamidine fujection 1872
Pentazocine 1873
Pentazocine Hydrochloride 1873
Pentazocine Tablets 1874
Pentazocine Lactate 1875
Pentazocine fujection 1876
Pentobarbitone Sodium 1877
Pentobarbitone Tablets 1877
Pepsin 1878

1847
MONOGRAPHS INDIAN PHARMACOPOEIA 2010

Peritoneal Dialysis Solutions 1879


Perphenazine 1881
Perphenazine Tablets 1882
Pethidine Hydrochloride 1883
Pethidine Injection 1884
Pethidine Tablets 1885
Phenindione 1886
Phenindione Tablets 1887
Pheniramine Maleate 1888
Pheniramine Injection 1889
Pheniramine Tablets 1889
Phenobarbitone 1890
Phenobarbitone Tablets 1891
Phenobarbitone Sodium 1891
Phenobarbitone Injection 1892
Phenobarbitone Sodium Tablets 1893
Phenol 1893
Phenolphthalein 1894
Phenoxyethanol 1895
PhenoxymethylpenicillinPotassium 1896
PhenoxymethylpenicillinPotassiumTablets 1897
Phentolamine Mesylate 1898
Phentolamine Injection 1899
Phenylephrine Hydrochloride 1899
Phenylephrine Injection 1900
PhenylmercuricAcetate 1901
Phenylmercuric Nitrate 1901
Phenylpropanolamine Hydrochloride 1902
Phenytoin 1903
Phenytoin Sodium 1904
PhenytoinInjection 1905
Phenytoin Capsules 1906
Phenytoin Tablets 1906

1848
INDIAN PHARMACOPOEIA 2010 MONOGRAPHS

Phenytoin Oral Suspension 1907


Pholcodine 1908
Pholcodine Linctus 1908·
Phosphoric Acid 1909
Physostigmine Salicylate 1910
Physostigmine fujection 1911
Pilocarpine Nitrate 1911
Pimozide 1912
Pimozide Tablets 1913
Pindolol 1914
Pindolol Tablets 1915
Pioglitazone HydrocWoride 1916
Pioglitazone Tablets 1917
Piperacillin 1918
Piperacillin futravenous Infusion 1919
PiperazineAdipate 1920
PiperazineAdipate Tablets 1921
Piperazine Citrate 1921
Piperazine Citrate Syrup 1922
Piperazine Hydrate 1923
Piperazine Phosphate 1924
Piperazine Phosphate Tablets 1924
Piracetam 1925
Piroxicam 1926
Piroxicam Capsules 1927
Plaster of Paris 1928
Poloxamer 1928 .
Polyethylene Glycol 1500 1929
Polyethylene Glycol 4000 1930
Polyethylene Glycol 6000 1930
Polyoxyl35 Castor Oil 1931
Polyoxyl40 Hydrogenated Castor Oil 1931
Polysorbate 20 1932
:1'~
1849
MONOGRAPHS INDIAN PHARMACOPOEIA 2010

Polysorbate 80 ~ ... 1932


Potassium CWoride 1933
Potassium Chloride and Dextrose Injection 1934
Potassium CWoride, Sodium Chloride and Dextrose Injection 1935
PotassiumCitrate 1936
Potassium Clavulanate 1937
Potassium Clavulanate Diluted 1938
Potassium Iodide 1939
Potassium·Permanganate 1940
Povidone 1941
Povidone..Iodine 1943
Povidone-Iodine Solution 1943
PralidoximeCWoride 1944
Pralidoxime CWoride Injection 1944
Pravastatin Sodium 1945
Pravastatin Tablets 1946
Praziquantel 1947
Praziquantel Tablets 1948
Prazosin HydrocWoride 1949
Prazosin Tablets 1950
Prednisolone 1951
Prednisolone Tablets 1952
Prednisolone Acetate 1954
Prednisolone Sodium Phosphate 1955
Prednisolone Sodium Phosphate Injection 1956
Prednisone 1957
Prednisone Tablets 1958
Pregabalin 1960
Pregabalin Capsules 1961
Pregelatinised Starch .... 1963
Primaquine Phosphate 1963
PrimaquineTablets 1964
Probenecid 1965

1850
INDIAN PHARMACOPOEIA 2010 MONOGRAPHS

Probenecid Tablets 1966


Procainamide Hydrochloride 1966
Procainamide fujection 1967
Procainamide Tablets 1968
Procaine Hydrochloride 1968
Procaine andAdrenaline fujection 1969
Procaine Penicillin 1970
Fortified Procaine Penicillin fujection 1971
ProchlOlperazine Maleate 1972
Prochlorperazine Tablets 1972
Prochlorperazine Mesylate 1973
Prochlorperazine fujection 1974
Procyclidine Hydrochloride 1974
Procyclidine Tablets 1975
Progesterone fujectable Suspension 1976
Proguanil Hydrochloride 1977
Proguanil Tablets 1977
Promazine Tablets 1978
Promethazine Hydrochloride 1979
Promethazine fujection 1979
Promethazine Syrup 1980
Promethaiine Tablets 1981
Promethazine Theoclate 1982
Promethazine Theoclate Tablets 1982
Propane 1983
Propionic Acid 1984
Propofol 1985
Propofol fujection 1986
Propranolol Hydrochloride 1987
Propranolol fujection 1988
Propranolol Tablets 1989
Propyl Gallate 1990
Propylene Glycol 1990

1851
MONOGRAPHS INDIAN PHARMACOPOEIA 2010

Propylparaben 1991
Propylthiouracil 1992.
Propylthiouracil Tablets . 1993.
Propyphenazone 1994
Protamine Sulphate 1995
Protamine Sulphate Injection 1996
Prothionamide 1996
Prothionamide Tablets 1997
Protriptylihe HydrocWoride 1998
Protriptyline Tablets 1999
Pseudoephedrine HydrocWoride 1999
Pseudoephedrine Syrup 2000
Pseudoephedrine Tablets 2001
Psoralen 2001
Pyrantel Pamoate .... 2002
Pyrante1Pamoate Oral Suspension 2003
Pyrazinamide 2004
Pyrazinamide Tablets 2005
Pyridoxine HydrocWoride ·2005
Pyridoxine Tablets 2006
Pyrimethamine 2007
Pyrimethamine Tablets ..... 2008
Pyrimethamine and Sulphadoxine Tablets .... 2009

1852
IP 2010 PACLITAXEL

Paclitaxel Chromatographic system


- a stainless steel column 15 em x 4.6 mm, packed with
Taxo! octadecylsilane bonded to porous silica(3/lm),
column temperature. 35°,
mobile phase: A. a mixture of 60 volumes of water and
40 volumes of acetonitrile,
B. acetonitrile
flow rate. 1.2 ml per minute,
a linear gradient programme using the conditions given
below,
spectrophotometer set at 227nm,
injection volume. 10 Ill.
Time Mobile phase A Mobile phase B
(in min) (per cent v/v) (per cent v/v)
o 100 O.
C47HsINOl4 Mol. Wt. 853.9
20 100 o
Paclitaxel is 5~,20-epoxy-l,2a;4,7 f3,lOf3,13a-hexahydroxytax-
60 10 90
ll-en-9-one 4,1 O-diacetate 2-benzoate 13-ester with(2R,3S)-
N-benzoyl-3-phenylisoserine. 62 100 o
A taxane derivative first isolated from the bark ofthe Pacific 70 100 o
yew tree, Taxus brevifolia. Inject reference solution (b). The test is not valid unless the
Paclitaxel contains not less than 97.0 per cent and not more resolution between the peak due to paclitaxel and 10-deacetyl-
than 102.0 per cent ofC47Hs1N014, calculated on the anhydrous 7-epipaclitaxel is not less than 1.2. The relative retention time
basis. for 10-deacetyl-7-epipaclitaxel is about 0.94 in respect to
paclitaxel.
Category. Anticancer.
Inject the test solution and reference solution (a). In the
Description. A white or almost white powder.
chromatogram obtained with the test solution, the area ofany
CAUTION - Paclitaxel is potentially cytotoxic. Great care secondary peak is not more than 0.5 times the area ofthe peak
should be taken in handling the powder and preparing in the chromatogram obtained with the reference solution (a)
solutions. (0.5 per cent) and the sum of areas of all the secondary peaks
is not more thantwi<;:e the area ofthe peak in the chromatogram
Identification
obtained with the reference solution (a) (2.0 per cent).
A. Determine by infrared absorption spectrophotometry (2.4.6).
Heavy metals (2.3.13). 1 g complies with the limittest for heavy
Compare the spectrum with that obtained with paciltaxel RS. metals, Method B (20ppm ). '
B. In the Assay, the principal peak in the chromatogram
Sulphated ash (2.3.18). Not more than 0.2 per cent. '
obtained withthe test solution corresponds to the peak inthe
chromatogram obtained with the reference solution. Water (2.3.43). Not more than 4.0 percent, determined on 0.1
g by coloumetry method.
Tests
Bacterial endotoxins (2.2.3). Not more than 0.4 Endotoxin Unit
Specific optical rotation (2.4.22). -49.00 to - 55.00 , determined per mg ofpaclitaxel.
in 1.0 per cent w/v solution in methanol.
Microbial contamination (2.2.9). The total viable aerobic count
Related substances. Determine by liquid chromatography
does not exceed 100 cfu per g. It meets the requirements ofthe
(2.4.14).
tests for the absence of Staphylococcus aureus, Pseudomonas
Test solution. Dissolve 10 mg ofsubstance under examination aeruginosa, Salmonella species, and Escherichia coli.
in 10 ml of acetonitrile.
Assay. Determine by liquid chromatography (2.4.14).
Reference solution (a). A 0.001 per cent w/v solution of
paclitaxel RS in acetonitrile. Solvent mixture. Dissolve 200 III of glacial acetic acid in
Reference solution (b). A solution containing 0.008 per cent 1000 ml of methanol.
w/vof 10 deacetyl-7-epipaclitaxel and 0.1 per cent w/v of Test solution. Dissolve 0.1 g of the substance under
paclitaxel RS in acetonitrile. examination in 100.0 ml in solvent mixture.

1853
PACLITAXEL INJECTION IP 2010

Reference solution. A 0.1 per cent w/v solution ofpaclitaxel Reference solution (b). A solution containing 0.006 per cent
RS in solvent mixture. w/v of 10 deacetyl-7-epipaclitaxel RS and 0.12 per cent w/v
of paclitaxel RS in acetonitrile.
Chromatographic system
a stainless steel column 25 ern x.4;6 mm, packed with Chromatographic system
pentafltioro phenyl groups bonded to porous silica (5 a stainless steel column 15 em x 4.6 mm, packed with
J.Ull), octadecylsilane bonded to porous silica (311m),
column temperature 35°, column temperature. 35°,
mobile phase: a mixture of 11 volumes of water and mobile phase: A. a mixture of 00 volumes of water and
9 volumes of acetonitrile, 40 volumes of acetonitrile,
flow rate. 1.5 rn1 per minute, B. acetonitrile,
spectrophotometer set at 227nm, flow rate. L2 rn1 per minute,
injection volume. 10 Ill. a linear gradient programme using the conditions given
below,
Inject the reference solution. The test is not valid unless the
- spectrophotometer set at 227 nm,
tailing factor is not more than L5. The relativestandard
deviation for replicate injections is not more than 2.0 per cent. injection volume. lO Ill.
Time Mobile phase A Mobile phase B
Inject the test solution and reference solution.
(in min) (per cent v/v) (percent v/v)
Calculate the content OfC47HsIN014.
o 100 o
Storage. Store protected from light, at a temperature not
exceeding 25°.
26 100 o
66 17 83
67 100 o
Paclitaxel Injection Inject reference solution (b). The test is not valid uniess the
resolution between the peak due to paclitaxel and 10-deacetyl-
Paclitaxel Injection is a sterile solution of Paclitaxel suitable 7-epipaclitaxel is not less than 1.2. The relative retention time
for dilution,for intravenous use. for 1O-deacetyl-7-epipaclitaxe1 is about 0.94 in respect to
Paclitaxel Injection contains not less than 90.0 per cent and paclitaxel.
not more than 110.0 per centofthestated amount of paclitaxel, Inject the test solution and reference solution (a). In the
C47HsIN014. . chromatogram obtained with the test solution, the area of any
Description. A clear colourless to slight yellow viscous secondary peak is not more than 0.8 times the area ofthe peak
solution. in the chromatogram obtained with the reference solution (a)
(0.8 per cent) and the sum of areas of all the secondary peaks
Identification is not more than twice the area ofthe peak in the chromatogram
obtained with the reference solution (a) (2.0 per cent).
In the Assay, the principal peak in the chromatogram obtained
with test solution corresponds to the peak in the chromatogram Other tests. Complies with the tests stated under Parenteral
obtained with reference solution. Preparations (Injections).

Tests Bacterial endotoxins (2.2.3). Not more than 0.67 Endotoxin


Unit per mg ofpaclitaxel.
pH (2.4.24). 3.0to 7.0, determined in a 10percentv/v solution
in water. Sterility (2.2.11). Complies with the test for sterility.

Light absorption. Absorbance of the injection at about 425 Assay. Determine by liquid chromatography (2.4.14).
nm, not more than 0.1. Solvent mixture. Dissolve 200 III of glacial acetic acid in
Related substances. Determine by liquid chromatography 1000 ml of methanol.
(2.4.14).
Test solution. Accurately measure the volume of injection
Test. solution. Accurately measure the volume of injection containing 6 mg ofPaclitaxel and dissolve in 10 ml ofsolvent
containing 12 mg of Paclitaxel, dilute to 10 rn1 with acetonitrile. mixture.
Reference solution (a). A 0.0012 per cent w/v solution of Reference solution. A 0.06 per cent w/v solution ofpaclitaxel
paclitaxel RS in acetonitrile. RS in solvent mixture.

1854
lP 2010 PANCREATIN

Chromatographic system and solution (2) to the remainder and maintain the mixtures at
a stainless steel column 30 cm x 3.9 mm, packed with 39° ± 1° for 5 minutes. To I ml of each mixture add 10 mlof
penta fluro phenyl group chemically bonded to porous iodinated potassium iodide solution. The liquid containing
silica'(5 jlm), solution (2) retains the colour of the solution of iodine and
column temperature 35°, the liquid containing solution (1) acquires an intense blue
mobile phase: a mixture of 11 volumes of water and 9 colour.
volumes of acetonitrile,
- flow rate. 1.5 ml per minute, Tests
- spectrophotometer set at 227nm, Fat. Not more than 5.0 per cent, determined by the following
- injection volume. 10 jll. method. Extract I g with light petroleum (40° to 60°) for
Inject the reference solution. The test is not valid unless the 3 hours in an apparatus for the continuous extraction ofdrugs
tailing factor is not more than 1.5. The relative standard (2.1.8), evaporate the extract and dry the residue at 105° for
deviation for replicate injections is not more than 2.0 per cent. 2 hours.
Inject the test solution and reference solution. Microbial contamination (2.2.9). 1g is free from Escherichia
coli; 10 g is free from Salmonellae.
Calculate the content ofC47HsINOI4.
Loss on drying (2.4.19). Not more than 5.0 per cent, determined
Storage. Store protected from light, at a temperature not
on 0.5 g by dying in an oven at 60° at a pressure not exceeding
exceeding 25°.
0.7 kPa for 4 hours.
Assay. For protease activity - Weigh accurately 4.0 g of
purified casein and dissolve in about 90 ml of water containing
Pancreatin 3 ml of1 M sodium hydroxide, adjust the pH ofthe solution to
8.7 and add sufficient water to produce 100.0 ml. Weigh
Pancreatin is a preparation ofmammalian pancreas containing accurately about 0.5 g of the substance under examination,
protease, lipase and amylase activity. It may contain Sodium triturate with water and add sufficient water to produce
Chloride. 300.0 ml to give the test solution. Dilute 15.0 ml ofthe casein
Pancreatin contains not less than the minimum protease solution with 30 ml of water, warm to 55° and add 10.0 ml ofthe
activity, amylase activity and lipase activity determined under unfiltered test solution. Heat rapidly to 55° and keep at this
the conditions of the Assay. temperature for 20 minutes. Cool rapidly to room temperature.
Dilute a further portion of 15.0 ml ofthe casein solution with
Category. Digestive enzyme. 30 ml of water, add 10.0 ml of the unfiltered test solution,
Dose. 500 mg to 1g. previously boiled and cooled, heat rapidly to 55° and keep at
this temperature for 20 minutes. Cool to room temperature. To
Description. A white or buff-coloured, amorphous powder;'
each solution add 0.75 ml ofphenolphthalein solution and 10
odour, meaty and not unpleasant. ml ofJormaldehyde solution. Titrate each solution with 0.1 M
sodium hydroxide until the colour of the solution matches
Identification
that produced by mixing 10 ml of buffer solution pH 8.7 and
A. Triturate 0.5 g with 10 ml of water and adjust to pH 8.0 by 0.15 ml of phenolphthalein solution. The difference between
the addition of 1 M sodium hydroxide using cresol red the two titrations is not less than 4.5 ml.
solution as indicator. Divide the resulting solution into two
For lipase activity- To 95 ml of water, add 6.5 mloftriacetin
equal portions. Boil one portion [solution (1)] and leave the and 0.2 ml ofa 0.1 per centw/v solution of bromocresolpurple,
other untreated [solution (2)]. To each add a few shreds of neutralise with 0.5 M sodium hydroxide and add sufficient
congo red fibrin, warm to 39° ± 1° and maintain at this
water to produce 110 mI. Place 50 ml ofthis solution in each of
temperature for 1 hour. Solution (2) is stained red and solution two large tubes 3 cm x 20 cm A and B contained in a thermostat
(1) is colourless or not more than slightly pink.
at 30°. Insert in each tube a rubber stopper having two holes,
B. Triturate 0.25 g with 10 ml of water and adjustto pH 8.0 by onefor the tip ofa burette and the other fora short glass tube
the addition of 1 M sodium hydroxide using cresol red through which passes a thread operating a glass stirring coil.
solution as' indicator. Divide the resulting solution into two Stir the contents of the tube until they attain the temperature
equal portions. Boil one portion [solution (1)] and leave the of the thermostat. Prepare a solution of 0.1 g ofthe substance
other untreated [solution (2)]. Dissolve 0.1 g ofsoluble starch under examination in 10.0 ml of water. To tube A add 1.0 ml of
in 100 ml ofboiling water, boil for 2 minutes, cool and dilute to the solution, to tube B add 1.0 ml of the solution previously
150 ml with water. Add solution (1) to halfthe starch mucilage boiled. Adjust and maintain the pH ofthe solutions in the two

1855
PANCREATIN IP 2010

tubes to 6.2 to 6.4 by the addition of 0.05 M sodium hydroxide Identification


dropwise, stirring frequently. After 30 minutes, the difference
Boil 50 mg with 5 ml of 0.1 M sodium hydroxide for 1 minute,
between the volumes of 0.05 M sodium hydroxide added to
cool and add 5 ml of1 M hydrochloric acid and 0.1 mlofjerric
the two tubes is not less than 1.0 ml.
chloride test solution; a deep yellow colour is produced.
For amylase activity- Not less than I00 Units per g. Dissolve
0.1 g or a quantity containing 10 Units, accurately weighed, in Tests
sufficient buffer solution pH 6.8 to produce 1000.0 ml. Filter if pH (2.4.24). Not more than 10.5, determined in a 5.0 percent
necessary (1 ml of the test solution should be capable of w/v solution in carbon dioxide-free water.
digesting about 10 mg of dry soluble maize or corn starch).
Into each of six stoppered test~tubes add 5.0 ml of starch Specific optical rotation (2.4.22). +28.2° to +30.2°, determined
substrate without touching the sides of the test-tube. Place at 20° in a 5.0 per cent w/v solution.
the test-tubes in a water-bath maintained at 40° ± 0.1°. When Refractive index (2.4.27). 1.490 to 1.498, determined at 20°.
the temperature of the solution in the tubes has reached 40°, Heavy metals (2.3.13). 1.0 g dissolved in 25 rnl ofwater complies
add 0.35 ml, 0.4 rnl, 0.45 rnl, 0.5 ml, 0.55 ml and 0.6 rnl ofthe test with the limit test for heavy metals, Method A (20 ppm).
solution to each of the test-tubes marked 1 to 6 respectively
and record the time of addition. Mix thoroughly and replace Assay. Weigh accurately about 0.5 g and carry out Method A
the tubes in the water-bath. After exactly 60 minutes remove for the determination ofnitrogen (2.3 .30).
the tubes and cool rapidly in cold water. Add to each tube 1 ml of 0.05 Msulphuricacidis equivalentto 0.001401 g ofN.
0.05 ml of 0.02 M iodine and mix well. Note the tube containing Storage. Store protected from moisture.
the lowest volume of test solution, which does not show a
bluish or violet tinge (if there is doubt, warm the solution
slightly, when the colour distinction is prominent). From this
volume calculate the number ofgrams ofdry soluble maize or Pantoprazole Sodium
corn starch digested by 1.0 g of the substance under
examination. This represents the number ofUnits of amylase
activity per g.
Storage. Store protected from moisture.
Labelling. The label states the name of any added substance.

Mol. Wt. 432.4


Pantoprazole Sodium is sodium 5-(difluromethoxy)-2[[(3,4
D-Panthenol
uimethoxy-pyridin-2-yl)methyl]sulphinyl]benzimidazol-1-ide,
Pantothenol; Dextro-pantothenyl Alcohol sesquihydrate.
Pantoprazole Sodium contains not less than 98.0 per cent and
not more than 102.0 per cent ofCI6HI4F2N3Na04S, calculated
on the anhydrous basis.
Category. Antiulcer.
Description. A white to off-white powder.
C9H I9N04 Mol. Wt. 205.3 Identification
D-Panthenol is (R)-2,4-dihydroxy-N-(3-hydroxypropyl)-3, 3- Test A may be omitted if tests Band C are carried out. Test B
dimethylbutanamide. may be omitted if tests A and C are carried out.
D-Panthenol contains not less than 6.60 per cent and not more A. Determine by infrared absorption spectrophotometry (2.4.6).
than 6.95 per cent of nitrogen, N. Compare the spectrum with that obtained with pantoprazole
Category. Vitamin B (enzyme co-factor). sodium RS or with the reference spectrum of pantoprazole
sodium.
Dose. 250 to 500 mg.
B. In the Assay, the principal peak in the chromatogram
Description. A clear, colourless or slightly yellow, viscous obtained with the test solution· corresponds to the principal
liquid; odourless. peak in the chromatogram obtained with the reference solution.

1856
IP 2010 PANTOPRAZOLE SUSTAINED-RELEASE TABLETS

C. Gives the reaction (a) ofsodium (2.3.1). Assay. Determine by liquid chromatography (2.4.14).

Tests Solvent mixture (a). Dilute 25.0 ml of ammonium hydroxide


to 500.0 ml with water.
Optical rotation (2.4.22). -0.40° to +0.40°, determined on 1.0
Solvent mixture (b). Equal volumes of acetonitrile and water.
per cent w/v solution.
Test solution. Dissolve about 20 mg of the substance under
Related substances. Determine by liquid chromatography
examination 10.0 ml ofsolvent mixture (b) and dilute to 50.0 ml
(2.4.14).
with solvent mixture (a). Dilute 3.0 ml ofthis solution to 20.0 ml
Solvent mixture. Equal volumes of acetonitrile and 0.001 M with solvent mixture (a).
sodium hydroxide.
Reference solution. Dissolve 20 mg of pantoprazole sodium
Test solution. Dissolve about 23 mg of the substance under RSin 10.0 ml of solvent mixture (b) and dilute to 50.0 ml with
examination in 50.0 ml ofthe solvent mixture. solvent mixture (a). Dilute 3.0 ml ofthis solution to 20.0 ml with
Reference solution. A 0.06 per cent w/v solution of solvent mixture (a).
pantoprazole sodium RS in the solvent mixture. Dilute 2.5 ml
Chromatographic system
ofthe solution to 50.0 ml with the solvent mixture.
- a stainless steel column 15 cm x 3.9 mm packed with
Chromatographic system octadecylsilane bonded to porous silica (4 Ilm) (Such
- a stainless steel column 12.5 cm x 4.0 mm packed with as Inertsil ODS-3),
octadecylsilane bonded to porous silica (5 Ilm) (Such - column temperature. 30°,
as Inertsil ODS-3), - sample temperature.4°,
- column temperature. 40°, mobile phase: A. a mixture of 85 volumes of buffer
- mobile phase: A. dissolve 1.74 g of dibasic potassium solution prepared by dissolving 1.32 g of dibasic
phosphate to 1000 ml with water; adjusted to pH ammonium phosphate to 1000 ml with water, adjusted
7.0 with orthophosphoric acid, to pH 7.5 with orthophosphoric acid and 15 volumes of
B. acetonitrile, acetonitrile,
- flow rate. 1 ml per minute, B. a mixture of7 volumes of acetonitrile
- spectrophotometer set at 290 run, and3 volumes of methanol,
- injection volume. 20 Ill. flow rate. 1 ml per minute,
Time Mobile phase A Mobile phase B - spectrophotometer set at 285 run,
(in min) (per cent v/v) (per cent v/v) - injection volume. 20 Ill.
040 80-720 20-780 Time Mobile phase A Mobile phase B
40-45 20 80 (in min) (per cent v/v) (per cent v/v)
45-55 20-780 80-720 0-10 86 14
Inject the reference solution. The test is not valid unless the 35 42 58
relative standard deviation for replicate injections is not more 36 86 14
than 2.0 per cent. 46 86 14
Inject the test solution and the reference solution. In the Inject the reference solution. The test is not valid unless the
chromatogram obtained with the test solution the area of the relative standard deviation for replicate injections is not more
peak due to impurity C determined at wavelength 305 nm at than 2.0 per cent.
relative retention time about 0.6 is not more than 0.77 times the
area of the principal peak at 290 nm in the chromatogram Inject the test solution and the reference solution.
obtained with reference solution (b) (0.5 per cent), the area of Calculate the content ofC16H14F2N3Na04S,
any secondary peak is not more than 0.077 times the area of
Storage. Store protected from light and moisture, between 2°
the principal peak in the chromatogram obtained with reference
to 8°.
solution (b) (0.5 per cent) and the sum of the areas of all the
secondary peaks is not more than 0.15 times the area of the
principal peak in the chromatogram obtained with reference
solution (b) (1.0 per cent).
Pantoprazole Sustained-release Tablets
Heavy metals (2.3.13). 1.0 g complies with the limit test for Pantoprazole Sodium Sustained-release Tablets
heavy metals, Method B (20 ppm). Pantoprazole Sustained-release Tablets contain not less than
Water (2.3.43). Not less than 5.0 per cent and not more than 90.0 per cent and not more than 110.0 per cent of the stated
8.0 per cent, determined on 0.15 g. amount ofpantoprazole, C16HlSF2N304S.

1857
PANTOPRAZOLE SUSTAINED-RELEASE TABLETS IP 2010

Usual strenth. 40 mg. Uniformity of content. Comply with the test stated under
Tablets.
Identification
Determine by liquid chromatography (2.4.14), as described in
A. In the Assay, the principal peak in the chromatogram the Assay using the following solutions.
obtained with the test solution corresponds to the principal
peak: in the chromatogram obtained with the reference solution. Test solution. Disperse 1 intact tablet in 100.0 ml ofthe mobile
phase and filter.
B. When examined in the range 230 urn to 350 nm (2.4.7), a
0.001 per cent w/v solution in methanol shows absorption Reference solution. Dissolve an accurately weighed quantity
maxima at about 289 urn. of pantoprazole sodium RS in the mobile phase and dilute
with the mobile phase to obtain a solution having a known
Tests concentration similar to the test solution.
Dissolution (2.5.2). Inject the reference solution and the test solution.
NOTE-Prepare the solutions immediately before use. Calculate the content ofCI6HIsF2N304S in the tablet.
Protect the solutions from light.
Other tests. Comply with the tests stated under Tablets.
A. Apparatus No.1,
Medium. 1000 ml of 0.1 M hydrochloric acid, Assay. Determine by liquid chromatography (2.4.14).
Speed and time. 100 rpm and 120 minutes. NOTE-Prepare the solutions immediately before use.
Determine by liquid chromatography (2.4.14). Protect the solutions from light.
Test solution. Withdraw the medium completely and disperse Test solution. Weigh and powder 20 tablets. Weigh accurately
the intact tablet in 100 ml of the mobile phase and filter. a quantity ofpowder containing about 20 mg ofPantoprazole
Sodium, disperse in 100 ml ofthe mobile phase and filter.
Reference solution. Dissolve an accurately weighed quantity
of pantoprazole sodium RS in the mobile phase and dilute Reference solution. A 0.02 per cent w/v solution of
with the mobile phase to obtain a solution having a known pantoprazole sodium RS in the mobile phase.
concentration similar to the test solution.
Chromatographic system
Use chromatographic system as described under Assay. stainless steel column 25 cm x 4.6 mm, packed with
Inject the reference solution and the test solution. octadecylsilane bonded to porous silica (5 Ilm) (such as
Inertsil ODS-3),
Calculate the content of CI6HISF2N304S released in the acid mobile phase: a mixture of50 volumes ofbuffer solution
medium by subtracting the content of CI6HISF2N304S in the prepared by dissolving 6.8 g of potassium dihydrogen
test solution from the total content of Pantoprazole, orthophosphate and. 1 g of hexane sulphonic acid
CI6HISF2N304S determined in the Assay. sodium salt in 1000 ml of water, adjusted to pH 7.3 with
D. Not more than 10 per cent of the stated amount of 1 M sodium hydroxide and 50 volumes of acetonitrile,
CI6HISF2N304S. flow rate. 1.5 m1 per minute,
spectrophotometer set at 290 urn,
B. Apparatus No.1,
injection volume. 10 Ill.
Medium. 1000 ml of tris-acetate buffer solution pH 8.5,
Inject the reference solution. The test is not valid unless the
Speed and time. 75 rpm and 60 minutes.
theoretical plates are not less than 2000, the tailing factor is
Run method A on another 6 tablets and discard the medium not more than 2.0 and the relative standard deviation for
completely and fill the empty vessel with the dissolution replicate injections is not more than 2.0 per cent.
medium. Withdraw a suitable volume ofthe medium and filter.
Dilute the filtrate, if necessary, with the dissolution medium. Inject the test solution and the reference solution.
Measure. the absorbance at the maximum at about 290 nm Calculate the content OfC16HISF2N304S in the tablets.
(2.4.7). Calculate the content ofC,6H,sF2N304S in the medium
from the absorbance obtained from a solution of known Storage. Store protected from moisture, at a temperature not
concentration of pantoprazole sodium RS. exceeding 30°.
D. Not less than 75 per cent of the stated amount of Labelling. The label states the strength in terms ofthe amount
CI6HISF2N304S. ofPantoprazole.

1858
IP 2010 PARACETAMOL

Paracetamol Related substances. Determine by liquid chromatography


(2.4.14).
Acetaminophen
Note-Prepare the solutions immediately before use.
Test solution. Dissolve 0.2 g of the substance under
examination in 2.5 ml of methanol containing 0.46 per cent
w/v of tetrabutylammonium hydroxide solution (40 per cent
w/v) and dilute to 10.0 ml with the solution containing equal
volumes of 1.79 per cent w/v ofdisodium hydrogenphosphate
and 0.78 per cent w/v of sodium dihydrogen phosphate.
Reference solution (a). Dilute 1.0 ml of the test solution to
50.0 ml with the mobile phase. Dilute 5.0 ml ofthis solution to
Mol. Wt. 151.2 100.0 ml with the mobile phase.

Paracetamol is 4-hydroxyacetanilide. Reference solution (b). Dilute 1.0 ml of reference solution (a)
to 10.0 ml with the mobile phase.
Paracetamol contains not less than 99.0 per cent and not more
than 101.0 per cent ofCsHgN02, calculated on the dried basis. Reference solution (c). Asolution containing 0.025 per cent
w/v each of 4-aminophenol, paracetamol RS and
Category. Analgesic; antipyretic. chloroacetanilide in methanol. Dilute 1.0 ml of this solution
Dose. 500 mg to I g every 4 to 6 hours, upto 4 g daily, in to 250.0 ml with the mobile phase.
divided doses
Reference solution (d). Dissolve 20 mg of 4-nitrophenol in
Description. White crystals or a white, crystalline powder. 50.0 ml of methanol. Dilute 1.0 ml ofthis solution to.20.0 ml
with the mobile phase.
Identification
Chromatographic system
TestA may be omitted if tests B C andD are carried out. Tests - a stainless steel column 25 cm x 4.0 rom, packed with
B, C and D may be omitted if test A is carried out. . octylsilane bonded to porous silica (5 /lm),
A. Determine by infrared absorption spectrophotometry (2.4.6). - column temperature. 35°,
Compare the spectrum with that obtained with paracetamol - mobile phase: a mixture of 37.5 volumes of a 1.79 per
RS or with the reference spectrum ofparacetamol. cent w/v solution of disodium hydrogen phosphate,
37.5 volumes of a 0.78 per cent w/v solution ofsodium
B. Dissolve 50 tng in sufficient methanol to produce 100 ml. dihydrogen phosphate and 25 volumes of methanol
To 1 ml ofthis solution add 0.5 m1 of0.1 M hydrochloric acid containing 0.46 per cent v/v of tetrabutylammonium
and dilute to 100 ml with methanol. Protect the resulting hydroxide solution (40 per cent w/v),
solution from bright light and immediately measure the - flow rate. 1.5 ml per minute,
absorbance at the maximum at about 249 nm; absorbance at - spectrophotometer set at 245 nm,
249 nm, about 0.44 (2.4.7). - injection volume. 20 Ill.
C. Boil 0.1 g in 1 ml of hydrochloric acid for 3 minutes, add
Inject reference solution (c). The test is not valid unless the
10 ml of water and cool; no precipitate is produced. Add
resolution between the peaks due to 4-aminophenol
0.05 ml of 0.0167 M potassium dichromate; a violet colour
(paracetamol impurity K) and paracetamol is not less than 4.0
develops which does not tum red.
and the signal-to-noise ratio of the peak due to
D. Gives the reaction of acetyl groups (2.3.1). chloroacetanilide (paracetamol imputity J) is not less than 50.
The relative retention time with reference to paracetamol for
Tests paracetamol impurity K is about 0.8, for 4-nitrophenol
(paracetamol impurity F) is about 3.0 and for paracetamol
4-Aminophenol. Dissolve 0.5 g in sufficient methanol (50 per
impurity J is about 7.0.
cent) to produce 10 ml. Add 0.2 ml offreshly prepared alkaline
sodium nitroprusside solution, mix and allow to stand for Inject the test solution, reference solution (a), (b) and (c). Run
30 minutes. Any blue colour in the solution is not more intense the chromatogram 12 times the retention time ofthe principal
than that in 10 ml of a solution prepared at the same time and peale In the chromatogram obtained with the test solution the
in the same manner containing 0.5 g of 4-aminophenol-free area ofthe peak due to paracetamol impurity J is not more than
paracetamol and 0.5 ml of a 0.005 per cent w/v solution of 0.2 times the area of the corresponding peak in the
4-aminophenol in methanol (50 per cent) (50 ppm). chromatogram obtained with reference solution (c) (10 ppm)

1859
PARACETAMOL SYRUP IP 2010

and the area ofthe peak due to paracetamol impurity K is not Reference solution. A 0.25 per cent w/v solution of
more than the area of the corresponding peak in the paracetamol RS in methanol
chromatogram obtained with reference solution (c) (50 ppm). Apply to the plate 10 III of each solution. After development,
The area of any other secondary peak is not more than 0.5 dry the plate in a current of warm air, examine in ultraviolet
times the area of the principal peak in the chromatogram light at 254 nm. The principal spot in the chromatogram
obtained with reference solution (a) (0.05 per cent). The sum obtained with the test solution corresponds to that in the
ofareas ofother secondary peaks is not more than the area of chromatogram obtained with the reference solution.
the principal peak in the chromatogram obtained with reference
solution (a) (0.1 per cent). Ignore any peak with an area less B. In the Assay, the principal peak in the chromatogram
than 0.5times the area ofthe principal peak in the chromatogram obtained with the test solution corresponds to the peak in the
obtained with reference solution (b) (0.01 per cent). chromatogram obtained with reference solution.
Heavy metals (2.3.13).2.0 g complies with the limit test for Tests
heavy metals, Method B (10 ppm).
4-Aminophenol. Determine by liquid chromatography (2.4.14).
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Test solution. Shake 5 ml ofthe preparation under examination
Loss on drying (2.4.19). Not more thanO.5 per cent, determined
with 15 ml ofthe mobile phase, dilute to 25 ml with the mobile
on 1.0 g by drying in an oven at 105°.
phase and filter if necessary.
Assay. Weigh accurately about 0.5 g, dissolve in a mixture of
Reference solution. A 0.0025 per cent w/v solution of
10 ml of water and 50 ml of 1 M sulphuric acid. Boil under a
4-aminophenol in the mobile phase.
reflux condenser for 1 hour, cool and dilute to 100.0 ml with
water. To 20.0 ml of the solution add 40 mlofwater, 40 g of Chromatographic system
water in the form of ice, 15 ml of 2 M hydrochloric acid and a stainless steel column 20 cm x 4.6 mm, packed with
0.1 ml of ferro in solution and titrate with 0.1 M eerie octadecylsilane bonded to porous silica (10 11m),
ammonium sulphate until a yellow colour is produced. Carry - mobile phase: 0.01 M sodium butanesulphonate in a
out a blank titration. mixture of85 volumes of water, 15 volumes of methanol
and 0.4 volume offormic acid,
1 ml of 0.1 M eerie ammonium sulphate is equivalent to
- flow rate. 2 ml per minute,
0.00756 gofCsHgN02 •
- spectrophotometer set at 272 urn,
Storage. Store protected from light and moisture. - injection volume. 20 Ill.
In the chromatogram obtained with the test solution the area
of any peak corresponding to 4-aminophenol is not greater
than the area of the peak in the chromatogram obtained with
Paracetamol Syrup the reference solution. In the chromatogram obtained with the
test solution peaks with a long retention time may occur due
Paracetamol Oral Solution; Acetaminophen Syrup
to preservatives in the preparations.
Paracetamol Syrup is a solution ofParacetamol in a suitable
Other tests. Complies with the tests stated under Oral Liquids.
flavoured vehicle. ,
Assay. Determine by liquid chromatography (2.4.14).
Paracetamol Syrup contains not less than 95.0 per cent and
not more than 105.0 per cent w/v solution ofthe stated amount Test solution. Mix an accurately weighed quantity of the
ofparacetamol, CsHgN0 2 • preparation under examination containing 25 mg of
Paracetamol in 100 ml ofthe mobile phase, dilute to 200.0 ml
Usual strength. 125 mgper 5 ml.
with the mobile phase and filter if necessary.
Identification Reference Solution. A 0.0125 per cent w/v solution of
paracetamol RS in the mobile phase.
A. Determine by thin-layer chromatography (2.4.17), coating
the plate with silica gel GF254. Chromatographic system
- a stainless steel column 20 cm x 4.6 mm, packed with
Mobile phase. A mixture of 65 volumes of chloroform,
octadecylsilane bonded to porous silica (10 11m),
25 volumes of acetone, 10 volumes of toluene and 0.5 volumes
- mobile phase: 0.01 M sodium butanesulphonate in a
of glacial acetic acid.
mixture of85 volumes of water, 15 volumes of methanol
Test solution. Dilute a volume containing 25 mg ofParacetamol and 0.4 volume offormic acid,
to 10 ml with methanol and filter ifnecessary. - flow rate. 2 ml per minute,

1860
IF 2010 PARACETAMOL TABLETS

- spectrophotometer set at 243 nm, test solution peaks with a long retention times may occur due
- injection volume. 20 !-d. to excipients.
Determine the weight per ml (2.4.29) ofthe syrup and calculate Related substances. Determine by liquid chromatography
the percentage content ofCsH 9N02, weight in volume. (2.4.14).
Storage. Store protected from light and moisture. Test solution. Disperse a quantity of powdered tablets
containing about 0.2 g ofParacetamol in 10.0 ml ofthe mobile
phase, filter.

Paracetamol Tablets Reference solution (a). Dilute 1 ml ofthe test solution to 20 ml


with the mobile phase. Dilute lml ofthis solution to 20 ml with
Acetaminophen Tablets the mobile phase.
Paracetamol Tablets contain not less than 95.0 per cent and Reference solution (b). A solution containing 0.002 per cent
not more than 105.0 per cent of the stated amount of w/v each of 4-aminophenol and paracetamol RS in the
paracetamol, CsH9N02 • mobile phase.
Usual strengths. 300 mg; 500 mg. Reference solution (c). ) A 0.00002 per cent w/v solution of 4-
chloroacetanilide in the mobile phase.
Identification
Chromatographic system
Extract a quantity ofthe powdered tablets containing 0.5 g of . - a stainless steel column 25 cm x 4.0 mm, packed with
Paracetamol with 20 ml of acetone, filter, evaporate the filtrate octylsilane bonded to porous silica (5 J.1m) (Such as
to dryness and dry at 105°. The residue complies with the Zorbax Rx C8),
following tests. - column temperature. 35 0,
A. Determine by infrared absorption spectrophotometry (2.4.6). - mobile phase: a mixture of 25 volumes of methanol
Compare the spectrum with that obtained with paracetamol containing 1.15 g of tetrabutylammonium hydroxide
RSor with the reference spectrum ofparacetamol. solution (40 per centw/v), with 37.5 volumes of 0.05 M
disodium hydrogen orthophosphate and 37.5 volumes
B. Boil 0.1 gin 1 ml of hydrochloric acid for 3 minutes, add
of 0.05 M sodium dihydrogen orthophosphate,
10 ml of water and cool; no precipitate is produced. Add
- flow rate. 1.5 ml per minute,
0.05 ml of 0.0167 M potassium dichromate; a violet colour
- spectrophotometer set at 245 nm,
develops which does not tum red.
- injection volume. 20 j..1l.
Tests Inject reference solution (b). The test is not valid unless the
4-Aminophenol. Determine by liquid chromatography (2.4.14). resolution between the two principal peaks is not less than
4.0.
Test solution. Shake a quantity of the powdered tablets
containing 1 g ofParacetamol with 15 ml of methanol, dilute to Inject the test solution and reference solution (a), (b) and (c).
100 ml with water and filter. Run the chromatogram 12 times the retention time of the
principal peak. In the chromatogram obtained with the test
Reference solution. A 0.001 per cent w/v solution of solution the area of peak corresponding to 4-aminophenol is
4-aminophenol in methanol (15 per cent). not more than the area ofthe corresponding peak in reference
Chromatographic system solution (b) (0.1 per cent), the area of peak corresponding to
- a stainless steel column 20 cm x 4.6 mm, packed with 4- chloroacetanilide is not more than the area of the principal
octadecylsilane bonded to porous silica (10 j..1m), peak in reference solution (c) (10 ppm) and the area of any
- mobile phase: 0.01 M sodium butanesulphonate in a other secondary peak is not more than the area ofthe principal
mixture of85 volumes of water, 15 volumes of methanol peak obtained with reference solution (a) (0.25 per cent).
and 0.4 volume offormic acid, Dissolution (2.5.2).
- flow rate. 2 ml per minute,
- spectrophotometer set at 272 nm, Apparatus. No 1
- injection volume. 20 J.1l. Medium. 900 ml ofphosphate bufferpH 5.8
Speed and time. 50 rpm and 30 minutes.
In the chromatogram obtained with the test solution the area
of any peak corresponding to 4-aminophenol is not greater Withdraw a suitable volume ofthe medium and filter and dilute
than the area of the peak in the chromatogram obtained with a suitable volume ofthe filtrate with the same solvent. Measure
the reference solution. In the chromatogram obtained with the the absorbance of the resulting solution at the maximum at

1861
HARD PARAFFIN IP 2010

about 243 nm (2.4.7). Similarly measure the absorbance of a Dose. 10 to 30 ml.


solution oflmown concentration ofparacetamol RS. Calculate
Description. A transparent, colourless, oily liquid~ free from
the content of CsHgNO z. fluorescence by daylight; odourless or almost odouiless.
D. Not less than 80 per cent ofthe stated amount ofCsHgNO z.
Tests
Other tests. Complies with the tests stated under Tablets.
Weight per ml (2.4.29). 0.860 g to 0.904 g.
Assay. Weigh and powder 20 tablets. Weigh accurately a
quantity ofthe powder containing about 0.15 g ofParacetamol, Dynamic viscosity (2.4.28). 110 mPas to 230 mPas, determined
at200±10 bymethodB or Viscosity (2.4.28). 10 cps to 40 cps,
add 50 mloiO.l M sodium hydroxide, dilute with 100 ml of
water, shake for 15 minutes and add sufficient water to produce determined at 30° ±l ° by method C using LVI spindle at 30
200.0 ml. Mix, filter and dilute 10.0 ml ofthe filtrate to 100.0 ml rpm.
with water. To 10.0 ml of the resulting solution add 10 ml of Acidity or alkalinity. To 10.0 g add 20 ml ofboiling water, heat
0.1 M sodium hydroxide, dilute to 100.0 ml with water and in a water-bath for 5 minutes, shake vigorously for 1 minute,
mix. Measure the absorbance of the resulting solution at the cool, allow to separate and filter the aqueous layer. To 10 ml of
maximum at about 257 nm (2.4.7). Calculate the content of the filtrate add 0.1 ml of phenolphthalein solution. The"
CsHgNO z taking 715 as the specific absorbance at 257 nm. solution is colourless and not more than 0.1 ml of 0.1 M sodium
hydroxide is required to change the colour of the solution to
Storage. Store protected from light and moisture.
pink.
Light absorption. When examined in the range 240 nrn to
280 nm (2.4.7), a 2.0 per cent w/v solution in 2,2,4-trimethyl-
Hard Paraffin pentane shows an absorption of not more than 0.1.
HardParaffin is a purified mixture of solid hydrocarbons Readily carbonisable substances. Place 5 ml in a dry, heat-
obtained from petroleum or from shale oil. resistant glass-stoppered test-tube (125 mm x 18 mm)
Category. Pharmaceutical aid(stiffening agent). previously rinsed with chromic acidsolution, then with water
and dried. Add 5 ml of nitrogen-free sulphuric acid
Description. A white or colourless, translucent mass, (containing 94.5 per cent to 95.5 per cent w/w ofHzS04), insert
frequently showing a crystalline structure; odourless even the stopper and shake as vigorously as possible in the
when freshly cut; slightly greasy to the touch. Bums with a longitudinal direction of the tube for 5 seconds. Loosen the
luminous flame. When melted, the liquid is free from stopper, immediately place the tube in a bath ofboiling water,
fluorescence by daylight. supporting it so as to prevent contact of the tube with the
bottom or side ofthe bath and heat for 10 minutes. At the end
Tests
of the second, fourth, sixth, and eighth minutes, remove the
Acidity or alkalinity. To 10.0 g add 20 ml ofboiling water, heat tube from the bath and shake as vigorously as possible in the
in a water-bath for 5 minutes, shake vigorously for I minute, longitudinal direction ofthe tube for 5 seconds. At the end of
cool, allow to separate and filter the aqueous layer. To 10 ml of 10 minutes from the time the tube was placed in the bath
the filtrate add 0.1 rnl of phenolphthalein solution. The remove the tube and allow to stand for 10 minutes. The lower
solution is colourless and not more than 0.1 ml of 0:1 M sodium acid layer is notmore intensely coloured than a mixture oD ml
hydroxide is required to change the colour of the solution to ofFCS, 1.5 ml ofCCS and 0.5 ml ofCSS (2.4.1), overlaid with
pink 5 ml ofliquid paraffin. lithe sulphuric acid remains dispersed
in the molten paraffin, the colour ofthe emulsion is not darker
Congealing range (2.4.10). 50° to 65°.
than that of the standard mixture when shaken vigorously.
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Solid paraffins. Place a suitable quantity, previously dried by
heating at 100° for 2 hours and cooled in a desiccator over
sulphuric acid, in a glass cylindrical vessel having an internal
Liquid Paraffin diameter ofapproximately 25 mm. Close the vessel and immerse
in a mixture of ice and water; after 4 hours the liquid is
White Mineral Oil; Liquid Petrolatum sufficiently clear that a black line, 0.5 mm in width, held vertically
Liquid Paraffin is a pmified mixture of liquid hydrocarbons behind the vessel is easily seen.
obtained from petroleum to which not more than 10 ppm of Sulphur compounds. Mix 4 ml with 2 ml of ethanol (95 per
. tocopherol or of butylated hydroxytoluene may be added. cent), and 2 drops of a clear, saturated solution of lead
Category. Laxative; faecal softener. monoxide iii sodium hydroxide solution and heat at 70° for

1862
IP 2010 WHITE SOFT PARAFFIN

10 minutes with frequent shaking; the mixture remains dispersed in the molten paraffin, the colour ofthe emulsion is
colourless. not darker than that of the standard mixture when shaken
Storage. Store protected from light. vigorously.
Solid paraffins. Place a suitable quantity, previously dried by
heating at 100° for 2 hours and cooled in a desiccator over
Light Liquid Paraffin sulphuric acid, in a glass cylindrical vessel having an internal
diameter ofapproximately 25 mm. Close the vessel and immerse
Light Mineral Oil; Light Liquid Petrolatum in a mixture of ice and water; after 4 hours the liquid is
sufficiently clear that a black line, 0.5 mm in width, held vertically
Light Liquid Paraffin is a purified mixture ofliquid saturated
behind the vessel is easily seen.
hydrocarbons obtained from petroleum. It may contain a
suitable stabiliser. Sulphur compounds. Mix 4 ml with 2 ml of ethanol (95 per
cent), and 2 drops of a clear, saturated solution of lead
Category. Pharmaceutical aid (vehicle).
monoxide in sodium hydroxide solution and heat at 70° for
Description. A transparent, colourless, oily liquid, free from 10 minutes with frequent shaking; the mixture remains
fluorescence by daylight; almost odourless when cold. colourless.

Tests Storage. Store protected from light.

Weight per ml (2.4.29).0.820 g to 0.880 g.


Dynamic viscosity (2.4.28). 25 mPas to 80 mPas, determined at Liquid Paraffin Emulsion
20° ±l ° by method B or Viscosity (2.4.28). 10 cps to 40 cps,
determined at 30° ±l ° by method C using LVI spindle at 30 Liquid Paraffm Oral Emulsion
rpm. Liquid Paraffin Emulsion is an oral emulsion ofLiquid Paraffin
Acidity or alkalinity. To 10.0 g add 20 ml ofboiling water, heat in Purified Water.
in a water-bath for 5 minutes, shake vigorously for 1 minute, Liquid Paraffin Emulsion contains not less than 44.0 per cent
cool, allow to separate and filter the aqueous layer. To 10 ml of and not more than 49.0 per cent w/w ofliquid paraffin.
the filtrate add 0.1 ml of phenolphthalein solution. The
Category. Laxative; faecal softener.
solution is colourless and not more than 0.1 ml of 0.1 M sodium
hydroxide is required to change the colour of the solution to Dose. 10 to 30 m!.
pink.
Tests
Light absorption. When examined in the range 240 nm to 280
nm (2.4.7), a 2.0 per cent w/v solution in 2,2,4-trimethylpentane Other tests. Complies with the tests stated under Oral Liquids.
shows an absorption of not more than 0.1. Assay. Weigh accurately about 5.0 g, add 10 ml ofwater, extract
Readily carbonisable substances. Place 5 ml in a dry, heat- with two quantities, each of40 ml, ofa mixture of2 volumes of
resistant glass-stoppered test-tube (125 mm x 18 mm) ethanol (95 per cent), 3 volumes of light petroleum (40° to
previously rinsed with chromic acid solution, then with water 60°) and 3 volumes of ether and then with 30 ml ofa mixture of
and dried. Add 5 ml of nitrogen-free sulphuric acid equal volumes of lightpetroleum (40° to 60°) and ether. Wash
(containing 94.5 per cent to 95.5 per cent w/w ofH 2S04), insert the combined extracts with 15 ml of 0.5 M sodium hydroxide
the stopper and shake as vigorously as possible in the and then with 15 ml of water, evaporate the solvent, add 5 ml
longitudinal direction of the tube for 5 seconds. Loosen the of acetone and evaporate again. Repeat the addition and
stopper, immediately place the tube in a bath ofboiling water, evaporation of acetone until the residue is free from water,
supporting it so as to prevent contact of the tube with the dry at 105° for 15 minutes and weigh.
bottom or side ofthe bath and heat for 10 minutes. At the end Storage. Store protected from moisture.
of the second, fourth, sixth, and eighth minutes, remove the
tube from the bath and shake as vigorously ssas possible in
the longitudinal direction of the tube for 5 seconds. At the
end of 10 minutes from the time the tube was placed in the White Soft Paraffin
bath remove the tube and allow to stand for 10 minutes. The
lower acid layer is not more intensely coloured than a mixture
White Petroleum Jelly
of3 ml ofFCS, 1.5 ml ofCCS and 0.5 ml ofCSS (2.4.1), overlaid White Soft Paraffin is a purified, semi-solid mixture of
with 5 ml of liquid paraffin. If the sulphuric acid remains hydrocarbons obtained from petroleum and bleached.

1863
WHITE SOFT PARAFFIN IP 2010

Category. Pharmaceutical aid (ointment base). the test substance at a spot 25 mID to 38 mm from the edge of
the container. Adjust the zero setting and quickly release the
Description. A white, translucent, soft unctuous mass,
plunger, then hold it free for 5 seconds. Secure the plunger
retaining these characteristics on storage and when melted
and read the total penetration from the scale. Make three or
. and allowed to cool without stirring; not more than slightly
more trials, each so spaced that there is no overlapping ofthe
fluorescent by daylight, even melted; odour1ess when rubbed
areas of penetration. Where the penetration exceeds 20 mID,
on the skin.
use a separate container of the test substance for each trial.
Tests Read the penetration to the nearest 0.1 mm. Calculate the
average of the three or more readings and conduct further
Melting range (2.4.21).38° to 56°, determined by Method IV trials to a total of 10 if the individual results differ from the
Acidity or alkalinity. To 10.0 g add 20 ml ofboiling water, heat average by more than ± 3 per cent. The final average of the
in a water-bath for 5 minutes, shake vigorously for 1 minute, trials is not less than 10.0 mID and not more than 30.0 mID
cool, allow to separate and filter the aqueous layer. To 10 ml of indicating a consistency value between 100 and 300.
the filtrate add 0.1 ml of phenolphthalein solution. The Sulphated ash (2.3.18). Not more than 0.1 percent.
solution is colourless and not more than 0.1 m1 of 0.1 M sodium
hydroxide is required to change the colour of the solution to Storage. Store protected from light and moisture.
pink.
Light absorption (2.4.7). Absorbance o(a 0.05 per cent w/v
solution in 2,2,4-trimethylpentane at about 290 nm, not more Yellow Soft Paraffin
than 0.5. Yellow Petroleum Jelly
Fixed oils, fats and resin. Digest 109 with 50 ml of sodium Yellow Soft Paraffin is a purified, semi-solid mixture of
-hydroxide solution at 100° for 30 minutes and allow the hydrocarbons obtained from petroleum.
aqueous layer to separate. On acidifYing the aqueous layer
with dilute sulphuric acid, no precipitate or oily matter is Category. Pharmaceutical aid (ointment base).
produced. Description. A pale yellow to yellow, translucent, soft
Foreign organic matter. Volatilises when heated, without unctuous mass, retaining these characteristics on storage and
emitting an acrid odour. when melted and allowed to cool without stirring; not more
than slightly fluorescent by daylight, even melted; odourless
Consistency. 100 to 300, determined by the following method. when rubbed on the skin.
Apparatus. The apparatus is essentially in agreement with IS
4887: 1980 and comprises a penetrometer fitted with a polished
Tests
cone-shaped metal plunger weighing 150 g having a detachable Melting range (2.4.21).38° to 56°, determined by Method IV.
steel tip of the following dimensions. The tip of the cone has
Light absorption (2.4.7). Absorbance of a 0.05 per cent w/v
an angle of 30°, the point being truncated to a diameter of
solution in 2,2,4-trimethylpentane at about 290 nm, not more
0.38 ± 0.08 mID, the base ofthe tip is 8.38 ± 0.13 mID in diameter
than 0.75.
and the length ofthe tip is 15 ± 0.25 mID. The remaining portion
ofthe cone has an angle of 90°, is 28 to 29 mm in height, and Acidity or alkalinity. To 10.0 g add 20 ml ofboiling water, heat
has a maximum diameter of65.1 mID at the base. The containers in a water-bath for 5 minutes, shake vigorously for 1 minute,
of the test are flat-bottomed metal or glass cylinders that are cool, allow to separate and filter the aqueous layer. To 10 ml of
102 ± 6 mID in diameter and not less than 60 mm in height. the filtrate add 0.1 ml of phenolphthalein solution. The
solution is colourless and not more than 0.1 ml of 0.1 M sodium
Procedure. Melt a sufficient quantity at a temperature below hydroxide is required to change the colour of the solution to
85° and pour into one or more ofthe containers filling to within pink.
6 mID ofthe rim. Cool to 25°± 2.so over a period ofnot less than
16 hours, protected from drafts. Two hours before the test, Fixed oils, fats and resin. Digest 109 with 50 ml of sodium
place the containers in a water-bath at 25° ± 0.5°. If the room hydroxide solution at 100° for 30 minutes and allow the
temperature is below 23.5° or above 26.5°, adjust the aqueous layer to separate. On acidifYing the aqueous layer
temperature of the cone to 25° ± 0.5° by placing it in a water- with dilute sulphuric acid, no precipitate or oily matter is
bath. produced.
Foreign organic matter. Volatilises when heated, without
Without disturbing the surface of the substance under
emitting an acrid odour.
examination, place the container on the penetrometer table,
and lower the cone until the tip just touches the top surface of Consistency. 100 to 300, determined by the following method.

1864
IP 2010 PARALDEHYDE

Apparatus. The apparatus is essentially in agreement with IS Tests


4887.1980 and comprises a penetrometer fitted with a polished
Paraffin Ointment complies with the tests stated under
cone-shaped metal plunger weighing 150 g having a detachable
Ointments.
steel tip of the following dimensions. The tip of the cone has
an angle of 30°, the point being truncated to a diameter of
0.38 ± 0.08 rom, the base ofthe tip is 8.38 ± 0.13 rom in diameter
and the length ofthe tip is 15 ±0.25 rom. The remaining portion Paraldehyde
of the cone has an angle of 90°, is 28 to 29 mm in height, and
has a maximum diameter of65.1 rom at the base. The containers
of the test are flat-bottomed metal or glass cylinders that are
102 ± 6 mm in diameter and not less than ,60 mm in height.
Procedure. Melt a sufficient quantity at a temperature below
85° and pour into one or more ofthe containers filling to within
Mol. Wt. 132.7
6 rom ofthe rim. Cool to 25°± 2S over a period ofnot less than
16 hours, protected from drafts. Two hours before the test, Paraldehyde is 2,4,6-trimethyl-1 ,3,5-trioxane, the cyclic trimer
place the containers in a water-bath at 25° ± 0.5°. If the room of acetaldehyde. It may contain a suitable amount of
temperature is below 23.5° or above 26.5°, adjust the antioxidant.
temperature of the cone to 25° ± 0.5° by placing it in a water- Category. Anticonvulsant in status epilepticus; hypnotic;
bath. sedative.
Without disturbing the surface of the substance under
Dose. By deep intramuscular injection, as a single dose, 5 to
examination, place the container on the penetrometer table, 10 ml; by rectal injection, 5 to 10 ml, suitably diluted with
and lower the cone until the tip just touches the top surface of physiological saline.
the test substance at a spot 25 mm to 38 mm from the edge of
the container. Adjust the zero setting and quickly release the Description. A colourless or slightly yellow, transparent liquid;
plunger, then hold it free for 5 seconds. Secure the plunger odour, strong and characteristic. Solidifies at low temperature
and read the total penetration from the scale. Make three or to form a crystalline mass.
more trials, each so spaced that there is no overlapping of the Identification'
areas of penetration. Where the penetration exceeds 20 rom,
use a separate container of the test substance for each trial. A. Heat 5 ml with 0.1 ml of 1 M sulphuric acid; acetaldehyde,
Read the penetration to the nearest 0.1 mm. Calculate the recognisable by its odour, is evolved.
average of the three or more readings and conduct further B. To 5 ml ofa 10 per cent v/v solution add 5 ml ofammoniacal
trials to a total of 10 if the individual results differ from the silver nitrate solution in a test-tube and heat on a water-bath;
average by more than ± 3 per cent. The final average of the metallic silver is deposited as a mirror on the sidesofthe tube.
trials is not less than 10.0 rom and not more than 30.0 mm
C. A 10 per cent w/v solution in carbon dioxide-free water is
indicating a consistency value between 100 and 300.
clear (2.4.1), but becomes turbid on warming.
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Tests
Storage. Store protected from light and moisture.
Congealing range (2.4.1 0). 10° to 13°.
Distillation range (2.4.8). Not more than 10 per cent distils
Paraffin Ointment below 123° and not less than 95 per cent distils below 126°.
Category. Pharmaceutical aid (ointment basis). Refractive index (2.4.27). 1.403 to 1.406.

White Beeswax 20 g Relative density (2.4.29).0.991 to 0.996.


Hard Paraffin 30 g Acetaldehyde. Shake 5 ml with a mixture of5 ml of ethanol
(60 per cent), 5 ml of hydroxylamine hydrochloride reagent
Cetostearyl Alcohol 50 g
in ethanol (60 per cent) and 2 drops of methyl orange solution
White Soft Paraffin· 900 g and titrate with 0.5 M sodium hydroxide to full yellow colour;
*May be replaced by Yellow Soft Paraffin ifother medicaments not more than 0.8 ml of 0.5 M sodium hydroxide is required.
to be incorporated are coloUred. Acidity. Mix 5 ml with 45 ml of carbon dioxide-free water and
Mix the ingredients, heat gently with stirring until titrate with 0.1 M sodium hydroxide using phenolphthalein
homogeneous and stir until cold. solution as indicator; not more than 1.5 ml is required.

1865
PARALDEHYDE IP 2010

Chlorides. To 5 ml ofa 1 per cent v/v solution add one drop of Identification
nitric acid and three drops of silver nitrate solution; no
opalescence is produced immediately. Test A may be omitted if test B, C and D carried out. Test D
may be omitted if test A, Band C are carried out.
Sulphates. To 5 ml ofa 1 per cent v/v solution add one drop of
hydrochloric acid and three drops of barium chloride A. Determine by thin layer chromatography (2.4.17), coating
solution; no turbidity is produced. the plate with silica gel G.
Peroxides. In a stoppered vessel, dissolve 5 ml in sufficient of Mobile phase. A mixture of 40 volumes of 1-butanol,
recently boiled and cooled water to produce 50 ml, add 5 ml of 10 volumes of glacial acetic acid and 10 volumes of water.
dilute sulphuric acid and 10 ml ofpotassium iodide solution. Test solution.. Dissolve 0.25 g of the substance under
Close the flask and set aside in the dark for 15 minutes. Titrate examination in 100 ml of wate]:
with 0.1 M sodium thiosulphate using starch solution as
indicator; set aside for 5 minutes and, if necessary, complete Reference solution. A 0.25 per cent w/v solution of
the titration. Not more than 2.0 ml of 0.1 M sodium penicillamine RS in water.
thiosulphate is required. Apply to the plate 2 III of each solution. Allow the mobile.
Non-volatile matter. Heat 5 ml in a small dish on a water-bath phase to rise 10 cm. Dry the plate at 105° for 5 to 10 minutes
and dry at 105° for 1 hour; the residue weighs not more than 3 and expose to iodine vapour for 5 to 10 minutes. The principal
mg (0.06 per cent w/v). spot in the chromatogram obtained with the test solution
corresponds to that in the chromatogram obtained with the
Storage. Store protected from moisture, in complete darkness
reference solution.
and at a temperature of8° to 15°. Ifsolidified, the whole ofthe
contents of the container should be liquified by warming B. Dissolve 0.5 g in a mixture of 0.5 ml of hydrochloric acid
before use. and 4 ml ofwarm acetone, cool in ice and scratch the inside of
the tube with a glass rod to initiate crystallisation; a white
NOTE - Do not use Paraldehyde if it has a brownish colour
precipitate is produced. Filter under vacuum, wash the
or an odour of acetic acid. Avoid contact with rubber and
precipitate with acetone and dry with suction. A 1 per cent
plastics.
w/v solution of the dried material is dextrorotatory.
Labelling. The label states (1) the nature and the proportion
of any antioxidant added; (2) that it may decompose on C. To 4 ml of a 1 per cent w/v solution add 2 ml of
standing to form potentially harmful substances. phosphotungstic acid solution and heat nearly to boiling; a
blue colour is produced.
D. In the testfor Penicillamine disulphide, the principal peak
Penicillamine in the chromatogram obtained with test solution (b)
corresponds to the peak due to penicillamine in the
D-Penicillamine chromatogram obtained with reference solution (a).
CH s 0 Tests
HsC--L - Jl
HS/ ~N~~H Appearance ofsolution. A 10.0 per cent w/v solution in carbon
dioxide-free water (solution A) is clear (2.4.1), and not more
CsHIlNOzS Mol. Wt. 149.2 intensely coloured than degree 6 of the appropriate range of
reference solutions (2.4.1).
Penicillamine is 3-mercapto-o-valine.
Penicillamine contains not less than 98.0 per cent and not pH (2.4.24). 4.5 to 5.5, determined ina 1.0percentw/v solution.
more than 101.0 per cent ofCsH II NOzS, calculated on the dried Specific optical rotation (2.4.22). -61.0° to-65.0°, determined
basis. in a 5.0 per cent w/v solution in 1 M sodium hydroxide.
Category. Chelating agent in copper and lead poisoning; Heavy metals (2.3.13).10 ml ofsolution A, complies with the
antirheumatoid arthritic. limit test for heavy metals, Method D (20 ppm). Use lead
Dose. In poisoning, 500 mg to 2 g daily, in divided doses or in standard solution (2 ppm Pb) to prepare the standard.
accordance with the needs of the patient. In rheumatoid Mercuric salts. Determine by atomic absorption
arthritis, initial dose, 125 to 250 mg daily before food, increased spectrophotometry (2.4.2), using a solution prepared in the
gradually every 4 to 12 weeks until remission occurs; usual following manner. To 1.0 g ofthe substance under examination
maintenance dose, 500 to 750 mg daily. add 10 ml of water and 0.15 ml of perchloric acid and swirl
Description. A white or almost white, crystalline powder. until dissolution is complete. Add 1 ml of ammonium

1866
IP 2010 PENICILLAMINE

pyrrolidinedithiocarbamate solution that has been washed sensitivity and formation of clearly defined inhibition zones
three times immediately before use, each time with an equal ofsuitable diameter. Immediately pour the inoculated medium
volume of 4-methyl-2-pentanone. Mix, add 2 ml of 4-methyl- into five Petri dishes (10 cm in diameter) to give uniform layers
2-pentanone, shake for 1 minute, dilute to 25 mlwith water, 2 to 5 mm in depth. Alternatively, the medium may consist of
allow the layers to separate and use the 4-methyl-2-pentanone two layers, only the upper layer being inoculated. Store the
layer. Measure the absorbance at 254 nm using a mercury dishes so that no appreciable growth or death of micro-
hollow-cathode lamp and an air-acetylene flame and setting organisms occurs before use and so that the surface of the
the zero using a 4-methyl-2-pentanone layer obtained by medium is dry at the time of use. In each dish, place five
repeating the procedure described above but omitting the stainless steel hollow cylinders (6 mm in diameter) on the
substance under examination. For the standard solution surface ofthe medium evenly spaced on a circle with a radius
dissolve 0.108 g of yellow mercuric oxide in the minimum of about 25 mm and concentric with the dish. For each dish,
volume of 2 M hydrochloric acid, add sufficient water to place in separate cylinders 0.15 ml of each of the following
produce 1000.0 ml and treat suitable volumes in the same manner five solutions.
as the solution ofthe substance under examination (10 ppm). For solution (1) dissolve LO g of the substance under
Penicillamine disolphide. Determine by liquid examination in 8 ml ofphosphate buffer pH 2.5, add 8 ml of
chromatography (2.4.14). ether and shake vigorously for 1minute. Repeat the extraction
Test solution (a). Dissolve 40 mg of the substance under and combine the ether layers. Add 8 ml ofphosphate buffer
examination in 5 ml ofthe mobile phase, add 1 ml ofa 0.0025 pH 2.5, shake for 1 minute, allow to settle and separate the
per cent w/v solution of sulphanilamide (internal standard) ether layer quantitatively, taking care to eliminate the aqueous
in the mobile phase and dilute to 10 ml with the mobile phase. phase completely. (Penicillin is unstable at pH 2.5; carry out
the operations at this pH within 6 to 7 minutes). Add 8 mlof
Test solution (b). Dissolve 40 mg of the substance under phosphate bufferpH 6.0, shake for 5 minutes, allow to settle,
examination in the mobile" phase and dilute to 10 ml with the separate the aqueous layer and check that the pH is 6.0. For
same solvent. solution (2) add 20 III of pr:micillinase solution to 2 ml of
Reference solution (a). A 0.4 per cent w/v solution of solution (1) and incubate at 37° for 1 hour. For solution (3)
penicillamine RS in the mobile phase. dissolve 5 mg of benzylpenicillin sodium in 500 ml of
Reference solution (b). Add 1 m1 oftest solution (a) to 1 m10f phosphate buffer pH 6.0 and dilute 0.25 mlofthis solution to
a 0.04 per cent w/v solution ofpenicillamine disulphide RS in 200 ml with phosphate bufferpH 2.5. Carry outthe extraction
the mobile phase and dilute to 10 ml with the mobile phase. procedure described under solution (1) using 8 ml of this
solution and beginning at the words "add 8 ml ofether...". For
Chromatographic system solution (4) add 20 ml of penicillinase solution to 2 ml of
- a stainless steel column 25 cm x 5 mm, packed with solution (3) and incubate at 37° for 1 hour. Prepare solution (5)
octylsilane bonded to porous silica (5 to 10 Ilm), in the same manner as solution (1) but omitting the substance
- mobile phase: an equal volume of 0.2 per cent w/v under examination.
solution of methanesulphonic acid and 0.01 per cent
w/v solution of disodium edetate, Maintain the dishes at 30° for at least 24 hours. Measure the
- flow rate. 2 ml per minute, diameters ofthe zones ofinhibition to within 0.1 mm. The test
- spectrophotometer set at 220 nm, is not valid unless solution (3) gives a clear zone of inhibition
injection volume. 20 Ill. and solutions (4) and (5) give no zones ofinhibition. Ifsolution
(1) gives a zone ofinhibition it is caused by penicillin provided
In the chromatogram obtained with test solution (a) the ratio solution (2) gives no zone of inhibition. If this is the case, the
of the area of any peak corresponding to penicillamine average diameter of the zones of inhibition given by solution
disulphide to the area of the peak due to the internal standard (1) for the five Petri dishes is less than that given by solution
is not greater than the corresponding ratio in the chromatogram (3)(0.1 ppm).
obtained with reference solution (b).
Nutrient medium
Penicillin. Carry out the following procedure in a penicillin-
Peptone 5 g
free atmosphere and with equipment reserved for the test.
Yeast extract L5g
Sterilise the equipment at 180° for 3 hours and the buffer
solutions at 121° for 20 minutes before use. Meat extract L5g
Sodium chloride 3.5g
LiquefY a suitable nutrient medium such as that described
below and inoculate at a suitable temperature with a culture of Agar 15 g
Micrococcus flavus (ATCC 9341) to give 5 x 104 micro- Distilled water 1000 ml
organisms per ml or a quantity necessary to obtain the required Adjust the pH to 6.0

1867
PENICILLAMINE TABLETS IP 2010

Penillic acid. Absorbance of a 0.2 per cent w/v solution at Penicillamine disulphide. Determine by liquid
about 268 run, not more than 0.07 (2.4.7)(about0.5 per cent). chromatography (2.4.14).
Sulphated ash (2.3.18). Not more than 0.1 per cent. Test solution. Shake quantity of the powdered tablets
containing 40 mg of Penicillamine with 10 ml of the mobile
Loss on drying (2.4.19). Not morethan 0.5 per cent, determined
phase, filter and use the filtrate.
on 1.0 g by drying in an oven at 60° over phosphoruspentoxide
at a pressure not exceeding 0.7 kPa. Reference solution. A 0.004 per cent w/v solution of
penicillamine disulphide RS in the mobile phase.
Assay. Dissolve 0.1 gin 30 ml of anhydrous glacial acetic
acid Titrate with 0.1 M perchloric acid, determining the end- Chromatographic system
point potentiometrically (2.4.25). Carry out a blank titration. a stainless steel column 25 cm x 5 mm, packed with
octylsilane bonded to porous silica (5 to 10 /lm),
1 ml of 0.1 M perchloric acid is equivalent to 0.01492 g of
mobile phase: an equal volume of 0.2 per cent w/v
CsH11NOzS.
solution of methanesulphonic acid and 0.01 per cent
Storage. Store protected from moisture. w/v solution of disodium edetate,
flow rate. 2 ml per minute,
- spectrophotometer set at 220 run,
- injection volume. 20 /ll.
Penicillamine Tablets
In the chromatogram obtained with the test solution the area
D-Penicillamine Tablets of any peak corresponding to penicillamine disulphide is not
Penicillamine Tablets contain not less than 95.0 per cent and greater than the area ofthe principal peak in the chromatogram
not more than 105.0 per cent of the stated amount of obtained with the reference solution (1.0 per cent).
penicillamine, CsH11NOzS. The tablets are coated. Other tests. Complies with the tests stated under Tablets.
Usual strengths. 50 mg; 125 mg; 250 mg. Assay. Weigh and powder 20 tablets. Weigh accurately a
quantity of the powder containing 0.1 g of Penicillamine,
Identification
dissolve as completely as possible in 50 ml of water and filter.
A. Shake a quantity ofthe powdered tablets containing 20 mg Add to the filtrate 5 ml of1 M sodium hydroxide and 0.2 ml of
ofPenicillamine with 4 ml of water and filter. Add to the filtrate a 0.1 per cent w/v solution of dithizone in ethanol (95 per
2 ml of phosphotungstic acid solution and allow to stand for cent) and titrate with 0.02 M mercuric nitrate.
5 minutes; a blue colour is produced.
1 ml of 0.02 M mercuric nitrate is equivalentto 0.005968 gof
B. Dissolve a quantity of the powdered tablets containing CsH11NOzS.
10 mg ofPenicillamine in 5 ml of water and add 0.3 ml of5 M Storage. Store protected from moisture.
sodium hydroxide and 20 mg of ninhydrin; an intense blue or
violet-blue colour is produced immediately.

Tests Diluted Pentaerythritol Tetranitrate


Mercuric salts. Disperse a quantity of the powdered tablets
containing 1 g ofPenicillamine in 10 ml of water in a stoppered
flask, add 0.2 ml of9 M perchloric acid and swirl to dissolve.
Add 1 ml of ammonium pyrrolidinedithiocarbamate solution,
mix, add 2 ml of 4-methyl-2-pentanone, shake for 1 minute and
add sufficient water to produce 25 ml. Detennine by atomic
absorption spectrophotometry (2.4.2), using a mercury hollow-
cathode lamp and an air-acetylene flame and setting the zero
using a 4-methyl-2-pentanone layer obtained by repeating Diluted Pentaerythritol Tetranitrate is a dry mixture of2,2-
the procedure described above but omitting the substance bis(hydroxymethyl)propane-l ,3-diol tetranitrate with
under examination, measuring at 254 run. Use mercury solution Lactose or Mannitol or a mixture of Lactose and Starch or
AAS, suitably diluted with water, for the standard solutions, any other suitable inert excipients which permit safe
adjusted to contain the same concentrations of9 M perchloric handling.
acid, ammonium pyrrolidinedithiocarbamate solution and Diluted Pentaerythritol Tetranitrate contains not less than
4-methyl-2-pentanone as the solution under examination 95.0 per cent and not more than 105.0 per cent of the stated
(40 ppm). amount ofpentaerythritol tetranitrate, CsHgN40IZ'

1868
IP 2010 DILUTED PENTAERYTHRlTOL TETRANITRATE

Category. Antianginal. prepared potassium iodide and starch solution and examine
at 254 urn. The spot due to nitrate in the chromatogram obtained
Dose. The equivalent of 20 to 60 mg of pentaerythritol
with the test solution is not more intense than the spot in the
tetranitrate, three to four times daily.
chromatogram obtained with the reference solution (0.5 per
Description. A white or almost white, powder; odour, faint cent, calculated as potassium nitrate).
and mild.
Related substances. Determine by liquid chromatography
(2.4.14).
Identification
Test solution (a). Shake about 25 mg of the substance under
A. Transfer a quantity of powder containing 10 mg of examination in 20 ml of the mobile phase for 15 rp.inutes and
pentaerythritol tetranitrate to a medium porosity sintered-glass dilute to 25.0 ml with the mobile phase, filter.
filter, add 5 ml of dry acetone and collect the filtrate. Repeat
with two further quantities, each of 5 ml, of dry acetone and Test solution (b). Dilute 1.0 ml of test solution (a) to 10.0 ml
evaporate the combined filtrate at a temperature not exceeding with the mobile phase.
60°, with the aid of a gentle current of air, and dry the residue Reference solution (a). Dissolve a quantity of diluted
at 60° for 4 hours; the residue melts at 138° to 142°(2.4.21). pentaerythritol tetranitrate RS containing about 25 mg of
B. Suspend 10 mg ofthe residue obtained in test A in a mixture Pentaerythritol Tetranitrate in 20 ml of the mobile phase,
of2 ml of sulphuric acid and 1 ml of water; cool and carefully sonicate for 15 minutes and dilute to 25.0 ml with the mobile
overlay with 3 ml offerrous sulphate solution; a reddish brown phase.
colour is produced at the interface of the two liquids. Reference solution (b). Dilute 1.0 ml ofreference solution (a)
C. Determine by thin-layer chromatography (2.4.17), coating to 10.0 ml with the mobile phase.
the plate with silica gel GF254. Reference solution (c). Dilute 0.3 ml ofreference solution (b)
Mobile phase. A mixture of20 volumes of ethyl acetate and 80 to 10.0 ml with the mobile phase.
volumes of toluene. Reference solution (d). Dilute 200 III of glyceryl trinitrate
Test solution. Dissolve a quantity of the substance under solution RS to 25.0 ml with the mobile phase.
examination containing about 10 mg of Pentaerythritol Reference solution (e). To 1 ml of reference solution (b), add
Tetranitrate in 10 ml of ethanol (95 per cent), filter. 1 ml of reference solution (d) and dilute to 10.0 ml with the
Reference solution. Shake a quantity of diluted mobile phase.
pentaerythritol tetranitrate RS containing about 10 mg of Reference solution (f). Dilute 1.0 ml ofreference solution (a)
Pentaerythritol Tetranitrate with 10 ml of ethanol (95 per to 20.0 ml with the mobile phase. Dilute 0.5 ml ofthis solution
cent). to 50.0 ml with the mobile phase.
Apply to the plate 10 III of each solution. Allow the mobile Chromatographic system
phase to rise 8 cm. Dry the plate in air and examine at 254 urn, - a stainless steel column 15 cm x 3.9 mm, packed with
The principal spot in the chromatogram obtained with the test octylsilane bonded to porous silica (5 11m),
solution corresponds to that in the chromatogram obtained - mobile phase: a mixture of 35 volumes of water and 65
with the reference solution. volumes of acetonitrile,
- flow rate. 1.4 ml per minute,
Tests - spectrophotometer set at 220 urn,
Impurity A. Determine by thin-layer chromatography (2.4.17), - injection volume. 20 Ill.
coating the plate with silica gel G. Inject reference solution (e). The test is not valid unless the
Mobile phase. A mixture of 15 volumes of glacial acetic acid, resolution between the peaks due to glyceryl trinitrate and
30 volumes of acetone and 60 volumes of toluene. pentaerythritol tetranitrate is not less than 3.0. The relative
retention time with reference to pentaerythritol tetranitrate for
Test solution. Dissolve about 0.1 g of the substance under
pentaerythritol tetranitrate impurity B is about 0.7 and for
examination in 5.0 ml of ethanol (95 per cent), filter.
pentaerythritol tetranitrate impurity C is about 0.3.
Reference solution. Dissolve about 10 mg ofpotassium nitrate
Inject test solution (a), reference solution (c) and (t). Run the
in I ml of water and dilute to 100 ml with ethanol (95 per
chromatogram 5 times the retention time ofthe principal peak.
cent).
In the chromatogram obtained with test solution (a) the area
Apply to the plate 10 III of each solution. Allow the mobile ofthe peak due to pentaerythritol tetranitrate impurity C is not
phase to rise 8 cm. Dry the plate in air and spray with freshly more than the area ofthe principal peak in the chromatogram

1869
PENTAERYTHRITOL TETRANlTRATE TABLETS IP 2010

obtained with reference solution (c) (0.3 per cent), the area of Transfer a portion of the mixture to a glass-stoppered
any other secondary peak is not more than not more than centrifuge tube and centrifuge at 1500 rpm for 5 minutes.
twice the area of the principal peak in the chromatogram Transfer 2.5 ml of the supernatant solution to a 100-ml
obtained with reference solution (t) (0.1 per cent). The sum of volumetric flask and evaporate at 35° with the aid ofa current
all the secondary peaks is not more than twice the area of the of air to dryness. To the residue add 1.0 m1 of glacial acetic
principal peak in the chromatogram obtained with reference acid and swirl to dissolve. Add 2 ml of phenoldisulphonic
solution (c) (0.6 per cent). Ignore any peak with an area less acidsolution, mix and allow to stand for 5 minutes. Add 25 ml
than the area of the principal peak in the chromatogram ofwater and 10 ml ofstrong ammonia solution, cool, dilute to
obtained with reference solution (t) (0.05 per cent). volume with water and mix. Measure the absorbance of the
Heavy metals (2.3.13). 2.0 g complies with limit test for heavy resulting solution at the maximum at about 409 nm (2.4.7),
metals, Method B (10 ppm). using water as the blank.
Weigh accurately 0.130 g of potassium nitrate, previously
Assay. Determine by liquid chromatography (2.4.14), as
dried at 105° for 4 hours, dissolve in 3 ml ofwater, dilute with
described in the test for Related substances.
sufficient glacial acetic acid to produce 200.0 ml and mix
Inject test solution (b) and reference solution (b). well. Using 1.0 ml of this solution repeat the procedure
Calculate the content ofCsHsN4012. beginning at the words "Add 2 ml ofphenoldisulphonic acid
solution,.......".Calculate the content ofCsHsN4012 in the tablet.
Storage. Store protected from light and moisture.
1 ml ofthe potassium nitrate solution is equivalent to 0.000503
NOTE - Undilutedpentaelythritol tetranitrate is a powerfUl g ofCsHsN40'2'
explosive. It can be exploded with percussion or excessive Other tests. Comply with the tests stated under Tablets.
heat. Great care and appropriate precautions should be
Assay. Weigh and powder 20 tablets. Weigh accurately a
taken in handling and only exceedingly small amounts should
quantity of the powder containing about 50 mg of
be isolated.
pentaerythritol tetranitrate and transfer to a 100-m1 volumetric
Labelling. The label states the percentage content of flask with the aid of about 30 ml of acetone. Add sufficient
pentaerythritol tetranitrate. acetone to produce 50 ml and warm on a water-bath at a
temperature not exceeding 60° and boil gently, with occasional
swirling, for 5 minutes. Cool, dilute to volume with acetone
and mix. Transfer a portion ofthe mixture to a glass-stoppered
Pentaerythritol Tetranitrate Tablets centrifuge tube and centrifuge at 1500 rpm for 5 minutes.
Pentaerythritol Tetranitrate Tablets contain not less than Transfer 1.0 ml of the supernatant solution to a 100-ml
90.0 per cent and not more than 110.0 per cent of the stated volumetric flask and evaporate at 35° with the aid ofa current
amount ofpentaerythritol tetranitrate, CsHsN 40 12 • of air to dryness. To the residue add 1.0 ml of glacial acetic
acid and swirl to dissolve. Add 2 ml of phenoldisulphonic
Usual strengths. 10 mg; 30 mg.
acidsolution, mix and allow to stand for 5 minutes. Add 25 ml
Identification ofwater and 10 ml ofstrong ammonia solution, cool, dilute to
volume with water and mix. Measure the absorbance of the
A. Transfer a quantity of powder containing 10 mg of
resulting solution at the maximum at about 409 urn (2.4.7),
pentaerythritol tetranitrate to a medium porosity sintered-glass
using water as the blank.
filter, add 5 ml of dry acetone and collect the filtrate. Repeat
Weigh accurately 0.13 g ofpotassium nitrate, previously dried
with two further quantities, each of 5 ml, of dry acetone and
evaporate the combined filtrate at a temperature not exceeding at 105° for 4 hours, dissolve in 3 ml of water, dilute. with
60°, with the aid of a gentle current of air, and dry the residue sufficient glacial acetic acid to produce 200.0 mland mix
at 60° for 4 hours; the residue melts at 138° to 142° (2.4.21). well. Using 1.0 ml of this solution repeat the procedure
beginning at the words "Add 2 ml ofphenoldisulphonic acid
Tests solution,.......".
Uniformity of content. (For tablets containing 10 mg or less) Calculate the content of CsHsN40 12 from the values of the
- Comply with the test stated under Tablets. absorbances so obtained.
1 ml of the potassium nitrate solution is equivalent to
Crush one tablet and transfer to a 50-ml volumetric flask with
0.000503 g ofCsHsN40 12 •
the aid of 15 m1 ofacetone. Add sufficient acetone to produce
25 ml, heat the mixture on a water-bath at a temperature not Storage. Store protected from light and moisture.
exceeding 60° and boil gently, with occasional swirling, for Labelling. The label states the strength in terms of the
5 minutes. Cool, dilute to volume with acetone and mix. equivalent amount of pentaerythritol tetranitrate.

1870
IP 20ra PENTAMIDINE ISETHIONATE

Pentamidine Isethionate and dilute to 50 ml with water. Dilute 1.0 ml ofthe solution to
50.0 ml with the mobile phase.
Chromatographic system
- a stainless steel column 25 cm x 4.6 mm packed with
octadecylsilane bonded to porous silica (5 ilm),
- mobile phase: a mixture of65 volumes of methanol and
Mol. Wt. 592.7 35 volumes of 3 per cent w/v solution of ammonium
acetate, adjusted to pH 7.5 with triethylamine,
Pentamidine Isethionate is 4,4' -[pentane-l ,5-diylbis(oxy)] - flow rate. 1 ml per minute,
bisbenzenecarboximidamide di(2-hydroxyethanesulphonate). - spectrophotometer set at 265 nm,
Pentamidine Isethionate contains not less than 98.5 per cent - injection volume. 10 ill.
and not more than 101.0 per cent ofC19H24N402, 2C2H 60 4S, Inject reference solution (b). The test is not valid unless the
calculated on the dried basis. resolution between the 2 principal peaks is not less than 2.0.
Category. Antiprotozoal. Inject the test solution and reference solution (a). Run the
Dose. By intramuscular injection, 3 to 4 mg per kg body weight chromatogram 3.5 times the retention time of the principal
daily for 10 days, maximum 200 mg. peale In the chromatogram obtained with the test solution,
the area of any secondary peak is not more than the area of
Description. A white or almost white powder or crystals;
the principal peak in the chromatogram obtained with reference
odourless or almost odourless; hygroscopic.
solution (a) (0.2 per cent), the sum of all the secondary peaks
is not more than twice the area of the principal peak in the
Identification
chromatogram obtained with reference solution (a) (0.4 per
A. Determine by infrared absorption spectrophotometry (2.4.6). cent). Ignore any peak with an area less than 0.1 times the area
Compare the spectrum with that obtained with pentamidine of the principal peak in the chromatogram obtained with
isethionate RS or with the reference spectrum ofpentamidine reference solution (a) (0.02 per cent).
isethionate. Ammonium isethionate. To 1.0 g in a test-tube (about 4 cm in
B. When examined in the range 230 om to 360 nm (2.4.7), a diameter) add 10 ml of water and 20 ml of 1 M sodium
0.001 per cent w/v solution in 0.01 Mhydrochloric acid shows hydroxide. Immediately attach a bung carrying a splash head
an absorption maximum only at about 262 om; absorbance at and an aspirator tube (about 5 mm in diameter).. Connect the
about 262 om, about 0.46). splash head to two test-tubes in series, each containing 20 ml
of 0.01 M sulphuric acid. Heat the tube containing the
C. To 10 ml ofa 0.05 per cent w/v solution add 1 ml ofa 0.1 per substance under examination in a water-bath at 45° to 50° and,
cent w/v solution of glyoxal sodium bisulphite and 1 ml of a maintaining this temperature, draw a current ofair, previously
solution prepared by dissolving 4 g of boric acid in a mixture passed through 1 M sulphuric acid, through the liquids in a
of 27 ml of 1 M sodium hydroxide and sufficient water to series of tubes for 3 hours at such a rate thatthe bubbles are
produce 100 ml. Heat on a water-bath for 10 minutes; a magenta just too rapid to count. Titrate the combined solutions from
colour is produced. the two absorption tubes with 0.02 M sodium hydroxide using
methyl red-methylene blue solution as indicator; not less than
Tests 36.5 ml of 0.02 M sodium hydroxide is required.
pH (2.4.24). 4.5 to 6.5, determined in a 5.0 percentw/v solution. Sulphated ash (2.3.18). Not more than 0.1 per cent.
Related substances. Determine by liquid chromatography Loss on drying (2.4.19). Not more than 4.0 per cent, determined
(2.4.14). on 1.0 g by drying in an oven at 105°.
Test solution. Dissolve about 0.1 g of the substance under Assay. Dissolve 0.250 g in 50 ml of dimethylformamide. Add
examination in 100.0 ml ofthe mobile phase. 0.25 ml of thymol blue solution and titrate with 0.1 M
tetrabutylammonium hydroxide, under a current of nitrogen,
Reference solution (a). Dilute 2.0 ml of the test solution to
until the colour of the indicator changes to blue. Carry out a
100.0 ml with the mobile phase. Dilute 1.0 ml ofthis solution to
blank titration.
10.0 ml with the mobile phase.
1 ml of 0.1 M tetrabutylammonium hydroxide is equivalent to
Reference solution (b). To 0.1 g in a conical flask, add 40 ml of
water and glass beads, adjusted to pH 10.5 with dilute sodium 0.02963 g ofC23H36N401OS2.
hydroxide solution and boil under reflux for 20 minutes. Cool Storage. Store protected from moisture.

1871
PENTAMIDINE INJECTION IP 2010

Pentamidine Injection Reference solution (b). Dissolve 0.1 g of substance under


examination in 40 ml of water, adjusted to pH 10.5 with 2 M
Pentamidine Isethionate Injection sodium hydroxide, heat under a reflux condenser for 20
Pentamidine Injection is a sterile material consisting of minutes, cool and dilute to 50 ml with water. Dilute 1.0 m1 of
Pentamidine Isethionate with or without buffering agents and this solution to 50.0 ml with the mobile phase.
other excipients. It is filled in a sealed container. Chromatographic system
The injection is constituted by dissolving the contents of the a stainless steel column 25 cm x 4.6 mm packed with
sealed container in the requisite amount of sterile Water for octadecylsilane bonded to porous silica (5 f!m) (Such
Injections, immediately before use. as Spherisorb ODS 1), .
mobile phase: a mixture of 130 volumes of methanol and
The constituted solution complies with the requirements for
70 volumes of3 per cent w/v solution of ammonium
Clarity of solution and Particulate matter stated under
acetate, adjusted to pH 7.5 with triethylamine,
Parenteral Preparations (Injections).
flow rate. 1 ml per minute,
Storage. The constituted solution should be used immediately spectrophotometer set at 265 nm,
after preparation but, in any case, within the period
injection volume. 10 f!l.
recommended by the manufacturer.
Inject reference solution (b). The test is not valid unless the
Pentamidine Injection contains not less than 95.0 per cent and
resolution between the two principal peaks is not less than
not more than 105.0 per cent of the stated amount of
2.0.
pentamidine isethionate, C19Hz4N40z, 2CzH 60 4S.
Usual strength. 200 mg. Inject the test solution and reference solution (a). Run the
chromatogram 3.5 times the retention time of the principal
The contents of the sealed container comply with the
peak. In the chromatogram obtained with the test solution the
requirements stated under Parenteral Preparations
area of any secondary peak is not more 0.2 times the area of
(Powders for Injection) and with thefollowing requirements.
the principal peak in the chromatogram obtained with reference
solution (a) (0.2 per cent) and the sum of the areas of all the
Identification
secondary peaks is not more than 0.4 times the area of the
A. Determine by infrared absorption spectrophotometry (2.4.6). principal peak in the chrotnatogram obtained with reference
Compare the spectrum with that obtained with pentamidine solution (a) (0.4 per cent).
isethionate RS or with the reference spectrum ofpentamidine
isethionate. Ammonium isethionate. To 1.0 g in a test-tube (about 4 cm in
diameter) add 10 ml of water and 20 ml of 1 M sodium
B. When examined in the range 230 nm to 360 nm (2.4.7), a hydroxide. Immediately attach a bung carrying a splash head
0.001 per cent w/v solution in 0.01 M hydrochloric acid shows and an aspirator tube (about 5 mm in diameter). Connect the
an absorption maximum only at about 262 nm; absorbance at splash head to two test-tubes in series, each containing 20 ml
about 262 nm, about 0.46. of 0.01 M sulphuric acid. Heat the tube containing the
C. To 10ml ofaO.05 per cent w/v solution add 1 m1 ofaO.1 per substance under examination in a water-bath at 45° to 50° and,
cent w/v solution of glyoxal sodium bisulphite and 1 ml of a maintaining this temperature, draw a current ofair, previously
solution prepared by dissolving 4 g of boric acid in a mixture passed through 1 M sulphuric acid, through the liquids in a
of 27 ml of 1 M sodium hydroxide and sufficient water to series of tubes for 3 hours at such a rate that the bubbles are
produce 100 ml. Heat on a water-bath for 10 minutes; a magenta· just too rapid to count. Titrate the combined solutions from
colour is produced. the two absorption tubes with 0.02 M sodium hydroxide using
methyl red-methylene blue solution as indicator; not less than
Tests 36.5 ml of 0.02 M sodium hydroxide is required.

pH (2.4.24). 4.5 to 6.5, determined in a5.0 per centw/v solution. Assay. Dissolve 0.25 g ofthe mixed contents of 10 containers
in 50 ml of dimethylformamide. Titrate with 0.1 M
Related substances. Determine by liquid chromatography
tetrabutylammonium hydroxide, determining the end-point
(2.4.14).
potentiometrically (2.4.25). Carry out a blank titration.
Test solution. Dissolve 0.1 g of substance under examination
in 100.0 ml ofthe mobile phase. 1 ml of 0.1 M tetrabutylammonium hydroxide is equivalent to
0.02963 g ofC,9Hz4N40z, 2CzH 60 4S.
Reference solution (a). Dilute 1 ml ofthe test solution to 100
ml with the mobile phase. Storage. Store in single dose containers.

1872
IP 2010 PENTAZOCINE HYDROCHLORIDE

Pentazocine Reference solution (b). A 0.01 per cent w/v solution of the
substance 'under examination in chloroform.
Reference solution (c). A 0.005 per cent w/v solution of the
substance under examination in chloroform.
Apply to the plate 10 III of each solution. After development,
dry the plate in air and examine in ultraviolet light at 254 nm.
Heat the plate at 105° for 15 minutes, allow to cool, expose to
iodine vapour and re-examine in ultraviolet light at 254 nm.
Any secondary spot in the chromatogram obtained with the
test solution is not more intense than the spot in the
Mol. Wt. 285.4
chromatogram obtained with reference solution (a); not more
Pentazocine is (2RS, 6RS, llRS)-6, II-dimethyl-3-(3-methylbut- than one such spot is more intense than the spot in the
2-enyl)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-01. chromatogram obtained with reference solution (b) and not
Pentazocine contains not less than 98.0 per cent and not more more than four such spots are more intense than the spot in
than 101.0 per cent ofC I9H27NO, calculated on the dried basis. the chromatogram obtained with reference solution (c).

Category. Narcotic analgesic. Sulphated ash (2.3.18). Not more than 0.1 percent.

Dose. By subcutaneous, intramuscular or intravenous Loss on drying (2.4.19). Not more than 1.0 per cent, determined
injection, 30 to 60 mg every 3 to 4 hours. on 1.0 g by drying in an oven at 60° at a pressure not exceeding
0.7 kPa for 4 hours.
Description. A white or pale cream powder.
Assay. Weigh accurately about 0.6 g, dissolve in 50 ml of
Identification anhydrous glacial acetic acid and titrate with 0.1 M perchlpric
acid, using crystal violet solution as indicator. Carry out a
A Determine by infrared absorption spectrophotometry (2.4.6).
blank titration.
Compare the spectrum with that obtained with pentazocine
RS or with the reference spectrum ofpentazocine. 1 ml of 0.1 Mperchloric acid is equivalent to 0.02854 g of
C I9H27NO.
B.To 1 mg in a porcelain crucible add 0.5 ml of a solution of
sulphuric acid containing 1 per cent w/v solution of Storage. Store protected from light and moisture.
ammonium molybdate; an intense blue colour is produced
which changes to bluish green, green and finally, on standing,
yellow.