TESTS
Appearance of solution. Dissolve 0.5 g in a mixture of
1 volume of methanol R and 4 volumes of tetrahydrofuran R
and dilute to 20 ml with the same mixture of solvents. The
solution is clear (2.2.1).
Related substances. Examine by thin-layer chromatography
(2.2.27), using silica gel GF254 R as the coating substance.
Prepare the solutions immediately before use and carry out
the test protected from light. D. 3-amino-6-bromo-4-(pyridin-2-yl)quinolin-2(1H)-one.
Test solution. Dissolve 50 mg of the substance to be
examined in a mixture of 1 volume of methanol R and
9 volumes of methylene chloride R and dilute to 5 ml with 01/2005:0706
the same mixture of solvents.
Reference solution. Dilute 1 ml of the test solution to 20 ml BROMHEXINE HYDROCHLORIDE
with a mixture of 1 volume of methanol R and 9 volumes of
methylene chloride R. Dilute 2 ml of the solution to 50 ml Bromhexini hydrochloridum
with a mixture of 1 volume of methanol R and 9 volumes of
methylene chloride R.
Apply separately to the plate 5 l of each solution. Develop
over a path of 7.5 cm using a mixture of 5 volumes of
alcohol R, 5 volumes of triethylamine R, 20 volumes of
methylene chloride R and 70 volumes of light petroleum R1.
Dry the plate in a current of air for 20 min and examine in
ultraviolet light at 254 nm. Any spot in the chromatogram
obtained with the test solution, apart from the principal
C14H21Br2ClN2 Mr 412.6
spot, is not more intense than the spot in the chromatogram
obtained with the reference solution (0.2 per cent). DEFINITION
Loss on drying (2.2.32). Not more than 0.2 per cent, N-(2-Amino-3,5-dibromobenzyl)-N-methylcyclohexanamine
determined on 1.000 g by drying at 80 C at a pressure not hydrochloride.
exceeding 2.7 kPa for 4 h. Content : 98.5 per cent to 101.5 per cent (dried substance).
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on 1.0 g. CHARACTERS
Appearance : white or almost white, crystalline powder.
ASSAY
Solubility : very slightly soluble in water, slightly soluble in
Dissolve 0.250 g in 20 ml of anhydrous acetic acid R. Add alcohol and in methylene chloride.
50 ml of acetic anhydride R. Titrate with 0.1 M perchloric
acid, determining the end-point potentiometrically (2.2.20). It shows polymorphism.
1 ml of 0.1 M perchloric acid is equivalent to 31.62 mg of IDENTIFICATION
C14H10BrN3O. First identification : A, E.
STORAGE Second identification : B, C, D, E.
Store protected from light. A. Infrared absorption spectrophotometry (2.2.24).
Comparison : bromhexine hydrochloride CRS.
IMPURITIES
If the spectra obtained in the solid state show differences,
dissolve the substance to be examined and the reference
substance separately in methanol R, evaporate to dryness
and record new spectra using the residues.
B. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 20 mg of the substance to be
examined in methanol R and dilute to 10 ml with the
same solvent.
Reference solution. Dissolve 20 mg of bromhexine
A. R = H : (2-amino-5-bromophenyl)(pyridin-2-yl)methanone, hydrochloride CRS in methanol R and dilute to 10 ml
B. R = CO-CH2-Cl : N-[4-bromo-2-(pyridin-2- with the same solvent.
ylcarbonyl)phenyl]-2-chloroacetamide, Plate : TLC silica gel F254 plate R.
Mobile phase : glacial acetic acid R, water R, butanol R
(17:17:66 V/V/V).
Application : 20 l.
Development : over 3/4 of the plate.
Drying : in air.
Detection : examine in ultraviolet light at 254 nm.
Results : the principal spot in the chromatogram obtained
with the test solution is similar in position and size to
C. 7-bromo-5-(6-methylpyridin-2-yl)-1,3-dihydro-2H-1,4- the principal spot in the chromatogram obtained with
benzodiazepin-2-one, the reference solution.
General Notices (1) apply to all monographs and other texts 1121