Monographs: Pharmaceutical substances: Busulfanum - Busulfan

Molecular formula. C₆H₁₄O₆S₂

Relative molecular mass. 246.3

Graphic formula.

Chemical name. 1,4-Butanediol dimethanesulfonate; tetramethylene dimethanesulfonate; CAS Reg. No. 55-98-1.

Other name. Myelosanum.

Description. A white, crystalline powder.

Solubility. Very slightly soluble in water; sparingly soluble in acetone R; slightly soluble in ethanol (~750 g/l) TS.

Category. Cytotoxic drug.

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

Additional information. CAUTION: Busulfan must be handled with care, avoiding contact with the skin and inhalation of airborne particles.

Requirements

Definition. Busulfan contains not less than 98.5% and not more than 100.5% of C₆H₁₄O₆S₂, calculated with reference to the dried substance.

Identity tests

A. Heat 0.1 g with 10 ml of water and 5 ml of sodium hydroxide (1 mol/l) VS until a clear solution is obtained; an intense odour of methanesulfonic acid is perceptible. Cool the solution and divide it into two equal portions for test B.

B. To one portion of the solution prepared in test A add 0.05 ml of potassium permanganate (10 g/l) TS; the purple colour changes to violet, then to blue, and finally to emerald-green. Acidify the second portion of the solution prepared in test A with 2 ml of sulfuric acid (~100 g/l) TS, add 0.05 ml of potassium permanganate (10 g/l) TS and shake; the colour of the permanganate is slowly discharged.

C. To a test-tube transfer 0.10 g of the test substance, suspend it in 1.0 ml of copper edetate TS and 0.5 ml of ammonia (~260 g/l) TS, then add 0.5 ml of hydrogen peroxide (~60 g/l) TS; this constitutes solution 1. Similarly, prepare a blank without the test substance; this constitutes solution 2. Place both tubes in a water-bath for 5 minutes, cool and add 1.0 ml of hydrochloric acid (~70 g/l) TS and 4.0 ml of barium chloride (50 g/l) TS; solution 2 remains clear and an opalescence is produced in solution 1, which changes to a white precipitate after a few minutes.

Melting range. 115 - 118 °C.

Sulfated ash. Not more than 1.0 mg/g.

Loss on drying. Dry to constant weight at 60 °C under reduced pressure (not exceeding 0.6 kPa or about 5 mm of mercury); it loses not more than 20 mg/g.

Assay. To about 0.25 g, accurately weighed, add 25 ml of water and boil gently under reflux for 30 minutes. Wash the condenser with a small quantity of water, cool, and titrate with carbonate-free sodium hydroxide (0.1 mol/l) VS, using phenolphthalein/ethanol TS as indicator. Repeat the operation without the substance being examined and make any necessary corrections. Each ml of carbonate-free sodium hydroxide (0.1 mol/l) VS is equivalent to 12.32 mg of C₆H₁₄O₆S₂.