(Ph. Eur. monograph 0358)
C11H12N4O2S 264.3 127-79-7
Action and use
Sulfonamide antibacterial.
DEFINITION
Sulfamerazine contains not less than 99.0 per cent and not more than the equivalent of 101.0 per cent of 4-amino-N-(4-methyl-2-pyrimidinyl)benzenesulfonamide, calculated with reference to the dried substance.
CHARACTERS
White, yellowish-white or pinkish-white, crystalline powder or crystals, very slightly soluble in water, sparingly soluble in acetone, slightly soluble in ethanol (96 per cent), very slightly soluble in methylene chloride. It dissolves in solutions of alkali hydroxides and in dilute mineral acids.
It melts at about 235 °C, with decomposition.
IDENTIFICATION
First identification: A, B.
Second identification: B, C, D.
A. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with sulfamerazine CRS. Examine the substances as discs.
B. Examine the chromatograms obtained in the test for related substances. The principal spot in the chromatogram obtained with test solution (b) is similar in position, colour and size to the principal spot in the chromatogram obtained with reference solution (a).
C. Place 3 g in a dry tube. Incline the tube by about 45°, immerse the bottom of the tube in a silicone-oil bath and heat to about 270 °C. The substance decomposes, producing a white or yellowish-white sublimate which, after recrystallisation from toluene R and drying at 100 °C, melts (2.2.14) at 157 °C to 161 °C.
D. Dissolve about 20 mg in 0.5 mL of dilute hydrochloric acid R and add 1 mL of water R. The solution gives, without further addition of acid, the identification reaction of primary aromatic amines (2.3.1).
TESTS
Appearance of solution
Dissolve 0.8 g in a mixture of 5 mL of dilute sodium hydroxide solution R and 5 mL of water R. The solution is not more intensely coloured than reference solution Y4, BY4 or GY4
(2.2.2, Method II).
Acidity
To 1.25 g, finely powdered, add 40 mL of carbon dioxide-free water R and heat at about 70 °C for 5 min. Cool for about 15 min in iced water and filter. To 20 mL of the filtrate add 0.1 mL of bromothymol blue solution R1. Not more than 0.2 mL of 0.1 M sodium hydroxide is required to change the colour of the indicator.
Related substances
Examine by thin-layer chromatography (2.2.27) using silica gel GF254 R as the coating substance.
Test solution (a): Dissolve 0.10 g of the substance to be examined in 3 mL of a mixture of 2 volumes of concentrated ammonia R and 48 volumes of methanol R and dilute to 5 mL with the same mixture of solvents.
Test solution (b): Dilute 1 mL of test solution (a) to 10 mL with a mixture of 2 volumes of concentrated ammonia R and 48 volumes of methanol R.
Reference solution (a): Dissolve 10 mg of sulfamerazine CRS in 3 mL of a mixture of 2 volumes of concentrated ammonia R and 48 volumes of methanol R and dilute to 5 mL with the same mixture of solvents.
Reference solution (b): Dilute 2.5 mL of test solution (b) to 50 mL with a mixture of 2 volumes of concentrated ammonia R and 48 volumes of methanol R.
Apply to the plate 5 μL of each solution. Develop over a path of 15 cm with a mixture of 3 volumes of dilute ammonia R1, 5 volumes of water R, 40 volumes of nitromethane R and 50 volumes of dioxan R. Dry the plate at 100 °C to 105 °C and examine in ultraviolet light at 254 nm. Any spot in the chromatogram obtained with test solution (a), apart from the principal
spot, is not more intense than the spot in the chromatogram obtained with reference solution (b) (0.5 per cent).
Loss on drying (2.2.32)
Not more than 0.5 per cent, determined on 1.000 g by drying in an oven at 105 °C.
Sulfated ash (2.4.14)
Not more than 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.2500 g in a mixture of 20 mL of dilute hydrochloric acid R and 50 mL of water R. Cool the solution in iced water.
Carry out the determination of primary aromatic amino- nitrogen (2.5.8), determining the end-point electrometrically.
1 mL of 0.1 M sodium nitrite is equivalent to 26.43 mg of C11H12N4O2S.
STORAGE
Store protected from light.
