Molecular formula. C₁₂H₁₄N₄O₄S

Relative molecular mass. 310.3

Graphic formula.

Chemical name. N ¹-(5,6-Dimethoxy-4-pyrimidinyl)sulfanilamide; 4-amino-N-(5,6-dimethoxy-4-pyrimidinyl)benzenesulfonamide; CAS Reg. No. 2447-57-6.

Description. A white or creamy white, crystalline powder; odourless.

Solubility. Very slightly soluble in water; slightly soluble in ethanol (~750 g/l) TS and in methanol R; practically insoluble in ether R.

Category. Antimalarial drug.

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

Requirements

Definition. Sulfadoxine contains not less than 99.0% and not more than 101.0% of C₁₂H₁₄N₄O₄S, calculated with reference to the dried substance.

Identity tests

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

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

B. About 0.05 g yields the reaction described for the identification of primary aromatic amines under 2.1 General identification tests, producing an orange-red precipitate.

C. Dissolve 50 mg in 3 mL of sodium hydroxide (0.1 mol/l) VS, heating slightly. Cool and add 1.0 mL of copper(II) sulfate (80 g/l) TS; a greenish yellow precipitate is produced, the colour of which changes to blue (distinction from certain other sulfonamides).

D. Melting temperature, about 199°C.

Heavy metals. Use 1.0 g for the preparation of the test solution as described under 2.2.3 Limit test for heavy metals, Procedure 4; determine the heavy metals content according to Method A; not more than 20 μg/g.

Chlorides. For the preparation of the test solution, boil 2.5 g with 30 mL of water, cool and filter. Add 10 mL of nitric acid (~130 g/l) TS to the filtrate and proceed as described under 2.2.1 Limit test for chlorides; the chloride content is not more than 0.1 mg/g.

Sulfates. For the preparation of the test solution, boil 2.5 g with 40 mL of water, cool and filter. Proceed with the nitrate as described under 2.2.2 Limit test for sulfates; the sulfate content is not more than 0.2 mg/g.

Clarity and colour of solution. A solution of 0.50 g in 10 mL of hydrochloric acid (~70 g/L) TS is clear and not more intensely coloured than standard colour solution Yw3 when compared as described under 1.11.1 Colour of liquids.

Sulfated ash. Not more than 1.0 mg/g.

Loss on drying. Dry to constant weight at 105°C; it loses not more than 5.0 mg/g.

Acidity. Heat 1.0 g with 50 mL of carbon-dioxide-free water R at about 70°C for 5 minutes, cool quickly to 20°C, and filter; titrate 25 mL of the filtrate to pH 7.0 with sodium hydroxide (0.1 mol/l) VS; not more than 0.25 mL is required.

Related substances. Carry out the test as described under 1.14.1 Chromatography, Thin-layer chromatography, using silica gel R3 as the coating substance and a mixture of 15 volumes of 1-butanol R and 3 volumes of ammonia (~17 g/l) TS as the mobile phase. Apply separately to the plate 10 μl of each of 2 solutions in a mixture of 9 volumes of ethanol (~750 g/l) TS and 1 volume of ammonia (~260 g/l) TS containing (A) 10 mg of the test substance per mL and (B) 0.050 mg of sulfanilamide RS per mL. After removing the plate from the chromatographic chamber, heat it at 105°C for 10 minutes and spray it with 4-dimethylaminobenzaldehyde TS3. Any spot obtained with solution A, other than the principal spot, is not more intense than that obtained with solution B.

Assay. Carry out the assay as described under 2.7 Nitrite titration, using about 0.5 g, accurately weighed, dissolved in a mixture of 75 mL of water and 10 mL of hydrochloric acid (~250 g/l) TS, and titrate with sodium nitrite (0.1 mol/l) VS. Each mL of sodium nitrite (0.1 mol/l) VS is equivalent to 31.03 mg of C₁₂H₁₄N₄O₄S.