Aminocaproic acid

EUROPEAN PHARMACOPOEIA 8.0

Temperature :

Column

Time
(min)
0-4

Temperature
(C)
130

4 - 6.5

130 180

6.5 - 11.5

180

Injection port

280

Detector

300

Detection : ame ionisation.

Injection : 2 L ; inject the test solution and reference
solution (c).
Retention time : internal standard = about 9.5 min.
Limits :
impurity C : calculate the ratio (R) of the area of the peak
due to impurity C to the area of the peak due to the internal
standard from the chromatogram obtained with reference
solution (c) ; calculate the ratio of the area of the peak due
to impurity C to the area of the peak due to the internal
standard from the chromatogram obtained with the test
solution : this ratio is not greater than R (10 ppm),
impurity D : calculate the ratio (R) of the area of the peak
due to impurity D to the area of the peak due to the internal
standard from the chromatogram obtained with reference
solution (c) ; calculate the ratio of the area of the peak due
to impurity D to the area of the peak due to the internal
standard from the chromatogram obtained with the test
solution : this ratio is not greater than R (10 ppm).
Iron (2.4.9) : maximum 40 ppm.
Dissolve 0.250 g in 3 mL of alcohol R and dilute to 10.0 mL
with water R.
Heavy metals (2.4.8) : maximum 20 ppm.
1.0 g complies with test C. Prepare the reference solution using
2 mL of lead standard solution (10 ppm Pb) R.
Water (2.5.12) : maximum 0.2 per cent, determined on 1.00 g.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g.

01/2008:0874
corrected 6.0

AMINOCAPROIC ACID
Acidum aminocaproicum
C6H13NO2
[60-32-2]

Mr 131.2

DEFINITION
Aminocaproic acid contains not less than 98.5 per cent and not
more than the equivalent of 101.0 per cent of 6-aminohexanoic
acid, calculated with reference to the dried substance.
CHARACTERS
A white or almost white, crystalline powder or colourless
crystals, freely soluble in water, slightly soluble in alcohol.
It melts at about 205 C with decomposition.
IDENTIFICATION
First identification : A.
Second identification : B, C, D.
A. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the spectrum obtained with
aminocaproic acid CRS. Examine the substances prepared
as discs.
B. Examine the chromatograms obtained in the test for
ninhydrin-positive substances. The principal spot in the
chromatogram obtained with the test solution (b) is similar
in position, colour and size to the principal spot in the
chromatogram obtained with reference solution (a).
C. Dissolve 0.5 g in 4 mL of a mixture of equal volumes of
dilute hydrochloric acid R and water R. Evaporate to dryness
by heating on a water-bath. Dry the residue in a desiccator.
Dissolve the residue in about 2 mL of boiling ethanol R.
Allow to cool and maintain at 4 C to 8 C for 3 h. Filter
under reduced pressure. The residue washed with about
10 mL of acetone R and dried at 60 C for 30 min, melts
(2.2.14) at 131 C to 133 C.
D. Dissolve about 5 mg in 0.5 mL of distilled water R. Add
3 mL of dimethylformamide R and 2 mL of ascorbic acid
solution R. Heat on a water-bath. An orange colour
develops.

ASSAY
Dissolve 0.100 g with heating in 50 mL of carbon dioxide-free
water R. Titrate with 0.1 M sodium hydroxide determining the
TESTS
end-point potentiometrically (2.2.20).
Solution S. dissolve 10.0 g in carbon dioxide-free water R and
1 mL of 0.1 M sodium hydroxide is equivalent to 13.71 mg
dilute to 50.0 mL with the same solvent.
of C7H7NO2.
Appearance of solution. Solution S is colourless (2.2.2,
Method II) and remains clear (2.2.1) on standing for 24 h.
STORAGE
pH (2.2.3). The pH of solution S is 7.5 to 8.0.
Protected from light.
Absorbance (2.2.25).
IMPURITIES
A. The absorbance of solution S at 287 nm is not more
than 0.10 and at 450 nm is not more than 0.03.
B. Place 2.0 g in an even layer in a shallow dish 9 cm in
diameter, cover and allow to stand at 98 C to 102 C for
72 h. Dissolve in water R and dilute to 10.0 mL with the
same solvent. The absorbance of the solution at 287 nm is
A. R = CO2H, R = NO2 : 4-nitrobenzoic acid,
not more than 0.15 and at 450 nm is not more than 0.03.
Ninhydrin-positive substances. Examine by thin-layer
chromatography (2.2.27), using a suitable silica gel as the
B. R = CO-O-C2H5, R = NH2 : ethyl 4-aminobenzoate
coating substance.
(benzocaine),
Test solution (a). Dissolve 0.10 g of the substance to be
examined in water R and dilute to 10 mL with the same
C. R = H, R = NH2 : aniline,
solvent.
Test solution (b). Dilute 1 mL of test solution (a) to 50 mL
with water R.
D. R = CH3, R = NH2 : 4-methylaniline (p-toluidine).
1540

See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 8.0

Aminoglutethimide

Reference solution (a). Dissolve 25 mg of

Reference solution (a). Dissolve 10 mg of aminocaproic
aminoglutethimide CRS in acetone R and dilute to
acid CRS in water R and dilute to 50 mL with the same solvent.
5 mL with the same solvent.
Reference solution (b). Dilute 5 mL of test solution (b) to
20 mL with water R.
Reference solution (b). Dissolve 25 mg of
aminoglutethimide CRS and 25 mg of glutethimide CRS in
Reference solution (c). Dissolve 10 mg of aminocaproic
acetone R and dilute to 5 mL with the same solvent.
acid CRS and 10 mg of leucine CRS in water R and dilute to
25 mL with the same solvent.
Plate : TLC silica gel F254 plate R.
Apply separately to the plate 5 L of each solution. Allow
Mobile phase : glacial acetic acid R, methanol R, ethyl
the plate to dry in air. Develop over a path of 15 cm using
acetate R (0.5:15:85 V/V/V).
a mixture of 20 volumes of glacial acetic acid R, 20 volumes
Application : 5 L.
of water R and 60 volumes of butanol R. Dry the plate in a
Development : over 3/4 of the plate.
current of warm air. Spray with ninhydrin solution R and heat
at 100 C to 105 C for 15 min. Any spot in the chromatogram
Drying : in air.
obtained with the test solution (a), apart from the principal
Detection : examine in ultraviolet light at 254 nm.
spot, is not more intense than the spot in the chromatogram
System suitability : reference solution (b) :
obtained with reference solution (b) (0.5 per cent). The test
the chromatogram shows 2 clearly separed spots.
is not valid unless the chromatogram obtained with reference
solution (c) shows two clearly separated principal spots.
Results : the principal spot in the chromatogram obtained
with the test solution is similar in position and size to
Heavy metals (2.4.8). 12 mL of solution S complies with test A
the principal spot in the chromatogram obtained with
for heavy metals (10 ppm). Prepare the reference solution
reference solution (a).
using lead standard solution (2 ppm Pb) R.
Loss on drying (2.2.32). Not more than 0.5 per cent,
TESTS
determined on 1.000 g by drying in an oven at 105 C.
Solution S. Dissolve 1.0 g in methanol R and dilute to 20.0 mL
Sulfated ash (2.4.14). Not more than 0.1 per cent, determined with the same solvent.
on 1.0 g.
Appearance of solution. Solution S is clear (2.2.1) and not
ASSAY
more intensely coloured than reference solution Y7 (2.2.2,
Method II).
Dissolve 0.100 g in 20 mL of anhydrous acetic acid R.
Using 0.1 mL of crystal violet solution R as indicator, titrate
Optical rotation (2.2.7): 0.10 to + 0.10, determined on
with 0.1 M perchloric acid until the colour changes from
solution S.
bluish-violet to bluish-green.
Related substances. Liquid chromatography (2.2.29).
1 mL of 0.1 M perchloric acid is equivalent to 13.12 mg of
Solvent mixture : methanol R, acetate buffer solution pH 5.0 R
C6H13NO2.
(50:50 V/V).
Test solution. Dissolve 0.100 g of the substance to be examined
01/2011:1291 in the solvent mixture and dilute to 50.0 mL with the solvent
mixture.
AMINOGLUTETHIMIDE
Reference solution (a). Dissolve 5.0 mg of aminoglutethimide
impurity A CRS in the solvent mixture and dilute to 25.0 mL
with the solvent mixture.
Aminoglutethimidum
Reference solution (b). Dilute 1.0 mL of reference solution (a)
to 10.0 mL with the solvent mixture.
Reference solution (c). Dilute 1.0 mL of the test solution to
100.0 mL with the solvent mixture.
Reference solution (d). Dilute 1.0 mL of the test solution to
10.0 mL with reference solution (a).
C13H16N2O2
Mr 232.3 Column :
[125-84-8]
size : l = 0.15 m, = 3.9 mm ;
DEFINITION
stationary phase : octadecylsilyl silica gel for
chromatography R (4 m) ;
(3RS)-3-(4-Aminophenyl)-3-ethylpiperidine-2,6-dione.

temperature
: 40 C.
Content : 98.0 per cent to 101.5 per cent (dried substance).
Mobile phase : mix 27 volumes of methanol R and 73 volumes
CHARACTERS
of acetate buffer solution pH 5.0 R.
Appearance : white or slightly yellow, crystalline powder.
Flow rate : 1.3 mL/min.
Solubility : practically insoluble in water, freely soluble in
Detection : spectrophotometer at 240 nm.
acetone, soluble in methanol.
Injection : 10 L of the test solution and reference solutions (b),
IDENTIFICATION
(c) and (d).
First identification : B.
Run time : 4 times the retention time of aminoglutethimide.
Second identification : A, C.
Identification of impurities: use the chromatogram obtained
A. Melting point (2.2.14) : 150 C to 154 C.
with reference solution (b) to identify the peak due to
impurity A.
B. Infrared absorption spectrophotometry (2.2.24).
Relative retention with reference to aminoglutethimide
Comparison : aminoglutethimide CRS.
(retention time = about 9 min) : impurity A = about 1.3.
C. Thin-layer chromatography (2.2.27).
System suitability : reference solution (d) :
Test solution. Dissolve 25 mg of the substance to be
examined in acetone R and dilute to 5 mL with the same
resolution : minimum 2.0 between the peaks due to
solvent.
aminoglutethimide and impurity A.
General Notices (1) apply to all monographs and other texts

1541