2020 Nimodipine 11-415

~OH Optical rotation (2.2.7)

-0.10° to + 0.10°, determined on solution S.
ozNMo
Related substances

6 Liquid chromatography (2.2.29).

Testsolution Dissolve 40 mg of the substance to be
examined in 2.5 mL oftetrahydrofuran R and dilute to
25.0 mL with the mobile phase.
G. 4-nitro- 2-phenoxyphenol.
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ PhEur Reference solution (a) Dilute 1.0 mL of the test solution to
100.0 mL with the mobile phase. Dilute 1.0 mL of this
solution to 10.0 mL with the mobile phase.
Reference solution (b) Dissolve 4 mg ofnimodipinefor peak
identification CRS (containing impurity C) in 0.25 mL of
Nimodipine tetrahydrofuran R and dilute to 2.5 mL with the mobile
(Ph. Bur. monograph 1245) phase.
Reference solution (c) Dilute 0.5 mL of the test solution to
25.0 mL with the mobile phase. Mix 0.5 mL of this solution
with 0.5 mL of nimodipine impurityA CRS and dilute to
10.0 mL with the mobile phase.
and enantiomer Column:
- size: 1= 0.125 m, 0 = 4.6 mm;
- stationary phase: end-capped octadecylsilyl silica gelfor
chromatography R (5 urn);
- temperature: 40°C.
418.4 66085-59-4 Mobile phase methanol R, tetrahydrofuran R, waterR
(20:20:60 V/V/V).
Action and use Flow rate 2.0 mUmin.
Calcium channel blocker.
Detection Spectrophotometer at 235 nm.
Preparations
Injection 20 IlL.
Nimodipine Infusion
Run time 4.5 times the retention time of nimodipine.
Nimodipine Tablets
Identification of impurities Use the chromatogram supplied
PhEur _ with nimodipine for peak identification CRS and the
DEFINITION chromatogram obtained with reference solution (b) to
identify the peak due to impurity C; use the chromatogram
2-Methoxyethyl 1-methylethyl (4RS)-2,6-dimethyl-4-(3-
obtained with reference solution (c) to identify the peak due
nitrophenyl)-l ,4-dihydropyridine-3,5-dicarboxylate.
to impurity A.
Content Relative retention With reference to nimodipine (retention
98.5 per cent to 101.5 per cent (dried substance).
=
time = about 7 min): impurity C about 0.5;
CHARACTERS impurity A = about 0.9.
Appearance System suitability Reference solution (c):
Light yellow or yellow, crystalline powder. - peak-to-valley ratio: minimum 4.0, where Hp = height
Solubility above the baseline of the peak due to impurity A and
Practically insoluble in water, freely soluble in ethyl acetate, H; = height above the baseline of the lowest point of the
sparingly soluble in anhydrous ethanol. curve separating this peak from the-peak due to
It shows polymorphism (5.9). nimodipine.
Exposure to ultraviolet light leads to the formation of a Limits:
nitrophenylpyridine derivative. - impurity C: not more than twice the area of the principal
peak in the chromatogram obtained with reference
IDENTIFICATION solution (a) (0.2 per cent);
A. Optical rotation (see Tests). - unspecified impurities: for each impurity, not more than
B. Infrared absorption spectrophotometry (2.2.24). the area of the principal peak in the chromatogram
Comparison nimodipine CRS. obtained with referencesolution (a) (0.10 per cent);
If the spectra obtained in the solid state show differences,
- total: not more than 5 times the area of the principal peak
record new spectra using 20 gIL solutions in methylene in the chromatogram obtained with reference solution (a)
(0.5 per cent);
chloride R and a 0.2 mm cell.
- disregard limit: 0.5 times the area of the principal peak in
TESTS the chromatogram obtained with reference solution (a)
Prepare solutions immediately before use either protected from light (0.05 per cent).
or underlong-wavelength light (> 420 nm). Loss on drying (2.2.32)
Solution S Maximum 0.5 per cent, determined on 1.000 g by drying in
Dissolve 1.0 g.in acetone R and dilute to 20.0 mL with the an oven at 105°C.
same solvent. Sulfated ash (2.4.14)
Appearance of solution Maximum 0.1 per cent, determined on 1.0 g.
Solution S is clear (2.2.1).

www.webofpharma.com
11-416 Nitrazepam 2020

ASSAY
Prepare solutions immediately before use either protected from light
Nitrazepam
or underlong-wavelength light (> 420 nm). (Ph. Bur. monograph 0415)
Dissolve with gentle heating 0.180 g in a mixture of 25 mL
of 2-methyl-2-propanol Rand 25 mL of perchloric acid
solution R. Add 0.1 mL oi ferroin R. Titrate with 0.1 M
cerium sulfate. Titrate slowly towards the end of the titration.
Carry out a blank titration.
1 mL of 0.1 M cerium sulfate is equivalent to 20.92 mg
of C21H26N207'
STORAGE
Protected from light. 281.3 146-22-5
IMPURITIES
Action and use
Specified impurities C. Benzodiazepine.
Otherdetectable impurities (thefollowing substances would, if
Preparations
present at a sufficient level, be detected by one or otherof the tests
Nitrazepam Oral Suspension
in the monograph. They are limited by the general acceptance
criterion for other/unspecified impurities and/orby the general Nitrazepam Tablets
monograph Substances for pharmaceutical use (2034). It is PhEur _
therefore not necessary to identify these impurities for
demonstration of compliance. See also 5.10. Control of impurities DEFINITION
in substances for pharmaceutical use) A, B. 7-Nitro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one.
Content
99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance
White or yellow, crystalline powder.
Solubility
Practically insoluble in water, slightly soluble in ethanol
(96 per cent).
A. 2-methoxyethyl 1-methylethyl 2,6-dimethyl-4-(3-
nitrophenyl)pyridine-3,5-dicarboxylate, IDENfIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison nitrazepam CRS.
TESTS
Related substances
Liquid chromatography (2.2.29). Carry out the testprotected
from light. -~.

Testsolution Dissolve 50 mg of the substance to be

B. bis(l-methylethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-
dihydropyridine-3,5-dicarboxylate,
C. bis(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-
dihydropyridine-3,5-dicarboxylate.
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ PhEur
examined in acetonitrile R and dilute to 20.0 mL with the
same solvent.
Reference solution (a) Dilute 1.0 mL of the test solution to
100.0 mL with acetonitrile R. Dilute 1.0 mL of this solution
to 10.0 mL vvith acetonitrile R.
Reference solution (b) Dissolve 2 mg of clonazepam CRS in
acetonitrile R and dilute to 100.0 mL with the same solvent.
Dilute 1.0 mL ofthis solution to 10.0 mL with the test
solution.
Column:
- size: 1= 0.25 m, 0 = 4.0 nun;
- stationary phase: octylsilyl silica gelfor chromatography R
(5 um);
- temperature: 40 "C.
Mobile phase:
- mobile phaseA: 7.8 gIL solution of sodium dihydrogen
phosphate R adjusted to pH 3.0 with phosphoric acid R;
- mobile phase B: acetonitrile R;

Time Mobile phase A Mobile phase B

(min) (per cent VIV) (per cent VIV)
0-3 65 35
3 - 10 65 -> 50 35 -> 50
10 - 20 50 50

www.webofpharma.com