Diazepam

EUROPEAN PHARMACOPOEIA 8.0

01/2008:0022

DIAZEPAM
Diazepamum
C. 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2carboxylic acid (rhein),

D. 5-acetoxy-4-hydroxy-9,10-dioxo-9,10-dihydroanthracene2-carboxylic acid (monoacetyl rhein isomer A),

E. 4-acetoxy-5-hydroxy-9,10-dioxo-9,10-dihydroanthracene2-carboxylic acid (monoacetyl rhein isomer B),

F. (10S)-3-(acetoxymethyl)-10-(2,3,4,6-tetra-O-acetyl--Dglucopyranosyl)-9-oxo-9,10-dihydroanthracene-1,8-diyl
diacetate (heptaacetyl aloin, heptaacetyl barbaloin),

G. 3-(acetoxymethyl)-10-(2,3,4,6-tetra-O-acetyl--Dglucopyranosyl)anthracene-1,8,9-triyl triacetate,

H. 3-(acetoxymethyl)-9,10-dioxo-9,10-dihydroanthracene1,8-diyl diacetate (triacetyl aloe-emodin).

2030

C16H13ClN2O
[439-14-5]

Mr 284.7

DEFINITION
7-Chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4benzodiazepin-2-one.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
Solubility : very slightly soluble in water, soluble in ethanol
(96 per cent).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison : diazepam CRS.
TESTS
Related substances. Liquid chromatography (2.2.29). Prepare
the solutions protected from bright light.
Test solution. Dissolve 25.0 mg of the substance to be
examined in 0.5 mL of acetonitrile R and dilute to 50.0 mL
with the mobile phase.
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 the contents of a vial of
diazepam for system suitability CRS (containing impurities A,
B and E) in 1.0 mL of the mobile phase.
Column :
size : l = 0.15 m, = 4.6 mm ;
stationary phase : spherical end-capped octylsilyl silica gel for
chromatography R (5 m) ;
temperature : 30 C.
Mobile phase : mix 22 volumes of acetonitrile R, 34 volumes of
methanol R and 44 volumes of a 3.4 g/L solution of potassium
dihydrogen phosphate R previously adjusted to pH 5.0 with
dilute sodium hydroxide solution R.
Flow rate : 1.0 mL/min.
Detection : spectrophotometer at 254 nm.
Injection : 20 L.
Run time : about 4 times the retention time of diazepam.
Identification of impurities : use the chromatogram
supplied with diazepam for system suitability CRS and the
chromatogram obtained with reference solution (b) to identify
the peaks due to impurities A, B and E.
Relative retention with reference to diazepam (retention
time = about 9 min) : impurity E = about 0.7 ; impurity A = about
0.8 ; impurity B = about 1.3.
System suitability : reference solution (b) :
resolution : minimum 2.5 between the peaks due to
impurities E and A and minimum 6.0 between the peaks
due to impurity A and diazepam.
See the information section on general monographs (cover pages)

Diazoxide

EUROPEAN PHARMACOPOEIA 8.0

Limits :
correction factors : for the calculation of content, multiply
the peak areas of the following impurities by the
corresponding correction factor : impurity B = 1.3 ;
impurity E = 1.3 ;
impurities A, B, E : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (a) (0.1 per cent) ;
C. 3-amino-6-chloro-1-methyl-4-phenylquinolin-2(1H)-one,
unspecified impurities : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (a) (0.10 per cent) ;
total : not more than twice the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.2 per cent) ;
disregard limit : 0.5 times the area of the principal peak in
the chromatogram obtained with reference solution (a)
(0.05 per cent).
E. 6-chloro-1-methyl-4-phenylquinazolin-2(1H)-one,
Heavy metals (2.4.8) : maximum 20 ppm.
2.0 g complies with test C. Prepare the reference solution using
4 mL of lead standard solution (10 ppm Pb) R.
Loss on drying (2.2.32): maximum 0.5 per cent, determined
on 1.000 g by drying in vacuo at 60 C for 4 h.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g.
F. 7-chloro-2-methoxy-5-phenyl-3H-1,4-benzodiazepine.
ASSAY
Dissolve 0.200 g in 50 mL of acetic anhydride R. Titrate
with 0.1 M perchloric acid, determining the end-point
potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 28.47 mg
of C16H13ClN2O.

01/2008:0550
corrected 6.0

DIAZOXIDE

STORAGE
Protected from light.
IMPURITIES
Specified impurities : A, B, E.
Other detectable impurities (the following substances would,
if present at a sufcient level, be detected by one or other of
the tests in the monograph. They are limited by the general
acceptance criterion for other/unspecied impurities and/or
by the general monograph Substances for pharmaceutical use
(2034). It is therefore not necessary to identify these impurities
for demonstration of compliance. See also 5.10. Control of
impurities in substances for pharmaceutical use) : C, D, F.

Diazoxidum

C8H7ClN2O2S
[364-98-7]

Mr 230.7

DEFINITION
Diazoxide contains not less than 98.0 per cent and
not more than the equivalent of 101.0 per cent of
7-chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide,
calculated with reference to the dried substance.
CHARACTERS
A white or almost white, ne or crystalline powder, practically
insoluble in water, freely soluble in dimethylformamide,
slightly soluble in alcohol. It is very soluble in dilute solutions
of the alkali hydroxides.

A. 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2one (nordazepam),

B. R = CO-CH2-Cl : 2-chloro-N-(4-chloro-2-benzoylphenyl)N-methylacetamide,
D. R = H : [5-chloro-2-(methylamino)phenyl]phenylmethanone,
General Notices (1) apply to all monographs and other texts

IDENTIFICATION
First identification : B.
Second identification : A, C, D.
A. Dissolve 50.0 mg in 5 mL of 1 M sodium hydroxide
and dilute to 50.0 mL with water R. Dilute 1.0 mL of
this solution to 100.0 mL with 0.1 M sodium hydroxide.
Examined between 230 nm and 350 nm (2.2.25), the
solution shows an absorption maximum at 280 nm and
a shoulder at 304 nm. The specic absorbance at the
maximum is 570 to 610.
B. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the spectrum obtained with
diazoxide CRS. Examine the substances prepared as discs
using potassium bromide R.

2031