Busulfan

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₆H₁₄O₆S₂  246.30

1,4-Butanediol, dimethanesulfonate;

1,4-Butanediol dimethanesulfonate CAS RN^®: 55-98-1; UNII: G1LN9045DK.

1 DEFINITION

Busulfan contains NLT 98.0% and NMT 100.5% of busulfan (C₆H₁₄O₆S₂), calculated on the dried basis.

2 IDENTIFICATION

2.1 A.

Sample: 100 mg

Analysis: Fuse the Sample with 100 mg of potassium nitrate and a pellet of potassium hydroxide weighing 250 mg. Cool, dissolve the residue in water, acidify with 3 N hydrochloric acid, and add a few drops of barium chloride TS.

Acceptance criteria: A white precipitate is formed.

2.2 B.

Sample: 100 mg

Analysis: Add 10 mL of water and 5 mL of 1 N sodium hydroxide to the Sample. Heat until a clear solution is obtained.

Acceptance criteria: An odor characteristic of methanesulfonic acid is perceptible.

2.3 C.

Sample solution: Use the solution from the Analysis in Identification test B.

Analysis: Cool the Sample solution, and divide it into two equal portions. To the first portion add 1 drop of potassium permanganate TS.

Acidify the second portion of the solution with 2 N sulfuric acid, and add 1 drop of potassium permanganate TS.

Acceptance criteria

For first portion: The purple color changes to violet, then to blue, and finally to emerald-green.

For second portion: The color of the permanganate is not discharged.

3 ASSAY

3.1 PROCEDURE

Sample solution: Transfer 80 mg of Busulfan into a 250-mL conical flask. Add 30 mL of water, swirl, add phenolphthalein TS, and neutralize with 0.05 N sodium hydroxide. Connect the flask to a reflux air condenser, and boil the mixture gently for NLT 30 min, adding water occasionally to maintain the volume. Cool to room temperature.

Titrimetric system

Mode: Direct titration

Titrant: 0.05 N sodium hydroxide VS

Endpoint detection: Visual

Analysis: Add phenolphthalein TS to the Sample solution, and titrate with Titrant. Each mL of Titrant is equivalent to 6.158 mg of busulfan (C₆H₁₄O₆S₂).

Acceptance criteria: 98.0%-100.5% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

5 SPECIFIC TESTS

MELTING RANGE OR TEMPERATURE (741): 115°-118°

LOSS ON DRYING (731)

Analysis: Dry a sample under vacuum at 60° to constant weight.

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

LABELING: The label bears a warning that great care should be taken to prevent inhaling particles of Busulfan and exposing the skin to it.