C₁₀H₉AgN₄O₂S

Relative molecular mass. 357.1

Chemical name. N ¹-2-Pyrimidinylsulfanilamide monosilver(1+) salt; 4-amino-N-2-pyrimidinylbenzenesulfonamide monosilver(1+) salt; CAS Reg. No. 22199-08-2.

Description. A white or almost white, crystalline powder.

Solubility. Sulfadiazine silver is practically insoluble in water and ethanol (~750 g/l) TS; slightly soluble in acetone R and ether R; soluble in ammonia (~260 g/l) TS.

Category. Anti-infective drug.

Storage. Sulfadiazine silver should be kept in a well-closed container, protected from light.

Requirements

Sulfadiazine silver contains not less than 98.0% and not more than 102.0% of C₁₀H₉AgN₄O₂S, calculated with reference to the dried substance.

Identity tests

• Either tests A and D or tests B, C, and D may be applied.

Prepare the following residue to be used in tests A, B, and C: dissolve 0.5 g in 5ml of nitric acid (~1000 g/l) TS, add 20 mL of water and 20 mL of sodium chloride (400 g/l) TS, mix, and filter. Neutralize the filtrate with sodium hydroxide (~80 g/l) TS using phenolphthalein/ethanol TS as indicator, and add 2.0ml of acetic acid (~60 g/l) TS; a white precipitate is produced. Filter, wash the precipitate on the filter with water, and dry it at 105 °C for 1 hour.

A. Carry out the examination with the residue as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from sulfadiazine RS or with the reference spectrum of sulfadiazine.

B. About 10mg of the residue yields the reaction described for the identification of primary aromatic amines under 2.1 General identification tests, producing an orange-red precipitate.

C. Dissolve about 0.1 g of the residue in 3 mL of water, add 3ml of sodium hydroxide (50 g/l) TS, shake, and filter. To a portion of the filtrate add 1 drop of copper(II) sulfate (160 g/l) TS; a yellowish green precipitate is produced that on standing turns to brownish red.

D. To about 0.1g add 20ml of water, 2 mL of nitric acid (~130 g/l) TS, and mix; a curdy, white precipitate is produced which is soluble in ammonia (~100 g/l) TS.

Loss on drying. Dry to constant mass at 80 °C; it loses not more than 5.0 mg/g.

pH value. Heat 1.0 g with 50 mL of carbon-dioxide-free water R to 70 °C for 5 minutes, cool rapidly, and filter. pH of the filtrate, 5.5-7.0.

Related substances. Carry out the test as described under 1.14.1 Chromatography, Thin-layer chromatography, using silica gel R4 as the coating substance and a mixture of 7 volumes of dichloromethane R, 4 volumes of methanol R, and 1 volume of ammonia (~260g/l) TS as the mobile phase. (Note: Mix the dichloromethane and methanol before adding the ammonia.) Apply separately to the plate 10μl of each of the following 2 solutions. For solution (A) dissolve 50mg of Sulfadiazine silver in 3.0 mL of ammonia (~260 g/l) TS and dilute with sufficient methanol R to produce 10 mL. For solution (B) dilute 1.0 mL of solution A with a mixture containing 4 volumes of methanol R and 1 volume of ammonia (~260 g/l) TS to produce 100 mL. Allow the spots to dry before development. After removing the plate from the chromatographic chamber, allow it to dry in air, and examine the chromatogram in ultraviolet light (254 nm).

Any spot obtained with solution A, other than the principal spot, is not larger and more intense than that obtained with solution B (1.0%).

Assay. Transfer into a stoppered flask about 0.5 g, accurately weighed, and dissolve in 8 mL of nitric acid (~130 g/l) TS. Add 50 mL of water and titrate with ammonium thiocyanate (0.1 mol/l) VS, using ferric ammonium sulfate (45 g/l) TS as indicator. Repeat the procedure without the Sulfadiazine silver being examined and make any necessary corrections.

Each mL of ammonium thiocyanate (0.1 mol/l) VS is equivalent to 35.71mg of C₁₀H₉AgN₄O₂S.