Molecular formula. C₅₁H₃₄N₆Na₆O₂₃S₆

Relative molecular mass. 1429

Graphic formula.

Chemical name. Hexasodium 8,8'-[ureylenebis[m-phenylenecarbonylimino(4-methyl-m-phenylene)carbonylimino]]di-1,3,5-naphthalenetrisulfonate; hexasodium 8,8'-[carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]]bis[1,3,5-naphthalenetrisulfonate]; CAS Reg. No. 129-46-4.

Other name. Nagananinum.

Description. A white, pinkish white or cream-coloured, crystalline powder; odourless.

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

Category. Antifilarial drug; antitrypanosomal drug.

Storage. Suramin sodium should be kept in a tightly closed container, protected from light.

Additional information. Suramin sodium is very hygroscopic and discolours on exposure to light.

Requirements

Definition. Suramin sodium contains not less than 96.0% and not more than 100.5% of C₅₁H₃₄N₆Na₆O₂₃S₆, calculated with reference to the anhydrous substance.

Manufacture. The method of manufacture is validated to demonstrate that the product, if tested, would comply with the following test.

Therapeutic potency. For therapeutic potency, the sample is tested in mice infected with a strain of Trypanosoma equiperdum, or other suitable species of trypanosome sensitive to suramin sodium. The test may be carried out as follows: Inoculate at least 10 mice with the trypanosomes. After forty-eight hours examine the blood of each mouse microscopically and estimate the number of trypanosomes per ml in the blood of each mouse. The number should lie between 1000 and 20 000. The estimate may be made by examining a thin film of the blood in the form of a cover-slip preparation, and counting the trypanosomes in at least 10 microscopic fields with an area of 0.12 mm². The presence of 1 to 20 trypanosomes in each of two fields corresponds approximately to a content of 1000 to 20 000 trypanosomes per ml.

Inject into 10 of the infected mice, intravenously, 0.16 ml of a 50 mg/l solution of the sample in freshly distilled water per g of body mass. Examine the blood of each mouse microscopically, using a microscope with a 4-mm objective, on the first and third days after the injection. If no trypanosomes are found in the blood of 5 or more mice when 20 fields are examined on the third day, the sample passes the test. If trypanosomes are found under these conditions in the blood of more than 5 mice, repeat the test. The sample passes the test if no trypanosomes are found under these conditions in the blood of not less than 50% of the total number of mice treated.

Identity tests

A. Dissolve 20 mg in 2.0 ml of water, add 1.0 ml of hydrochloric acid (~70 g/l) TS, and heat on a water-bath for 5 minutes. Cool, add 0.25 ml of sodium nitrite (10 g/l) TS, allow to stand for 1 minute, then add 1.0 ml of sodium hydroxide (~80 g/l) TS and 0.15 ml of 2-naphthol TS1; a red colour is produced.

B. In a porcelain crucible, mix 20 mg with 0.10 g of anhydrous sodium carbonate R and heat until the gas evolution has ceased. Cool, dissolve the residue in 4 ml of hydrochloric acid (~70 g/l) TS, and filter. To 2.0 ml of the nitrate add 0.25 ml of barium chloride (50 g/l) TS; a white precipitate is produced.

C. Dissolve 0.05 g in 2.0 ml of water and add 0.25 ml of glacial acetic acid R; it yields reaction B characteristic of sodium as described under 2.1 General identification tests.

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 3; determine the heavy metals content according to Method A; not more than 20 μg/g.

Chlorides. Dissolve 0.5 g in 10 ml of water, add 5 ml of nitric acid (~130 g/l) TS, 5 ml of silver nitrate (0.1 mol/l) VS, and 3 ml of nitrobenzene R, and shake vigorously. Titrate the excess of silver nitrate with ammonium thiocyanate (0.1 mol/l) VS, using 2 ml of ferric ammonium sulfate (45 g/l) TS as indicator; not less than 3.6 ml of ammonium thiocyanate (0.1 mol/l) VS are required.

Sulfates. Dissolve 0.50 g in 20 ml of water, add 3 ml of hydrochloric acid (~250 g/l) TS, and proceed as described under 2.2.2 Limit test for sulfates; the sulfate content is not more than 1 mg/g.

Clarity of solution. A solution of 0.50 g in 10 ml of carbon-dioxide-free water R is clear.

Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A, using about 0.2 g of the substance; the water content is not more than 0.10 g/g.

pH value. pH of a 10 mg/ml solution in carbon-dioxide-free water R, 5.5-7.0.

Free amines. Dissolve 5 g in 30 ml of water and add 30 ml of hydrochloric acid (1 mol/l) VS. Titrate at a temperature between 15 and 20°C with sodium nitrite (0.1 mol/l) VS, stirring vigorously, until a blue colour is obtained on starch/iodide paper R. The end-point of the titration is reached when the blue colour is reproduced after the titrated solution has been allowed to stand for 1 minute. The titration can also be performed electrometrically. Repeat the operation without the substance to be examined. The difference in volume between the two titrations does not exceed 0.4 ml.

Assay. To about 0.5 g, accurately weighed, add 12 ml of sulfuric acid (~700 g/l) TS, and boil under a reflux condenser for 1 hour; cool, and dilute to about 100 ml with water. Add 1 g of potassium bromide R and titrate at a temperature between 15 and 20°C with sodium nitrite (0.1 mol/l) VS, stirring vigorously until a blue colour is obtained on starch/iodide paper R. The end-point of the titration is reached when the blue colour is reproduced after the titrated solution has been allowed to stand for 1 minute. The titration can also be performed electrometrically. Repeat the operation without the substance to be examined. Each ml of sodium nitrite (0.1 mol/l) VS is equivalent to 23.82 mg of C₅₁H₃₄N₆Na₆O₂₃S₆.