Busulfan Tablets

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Busulfan Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of busulfan (C₆H₁₄O₆S₂).

2 IDENTIFICATION

2.1 A.

Sample: A suitable number of Tablets

Analysis: Pulverize the Sample and extract the powder with several portions of acetone. Evaporate the combined acetone extracts, with the aid of a current of air, on a steam bath.

Acceptance criteria: The dry residue melts at about 115°.

2.2 B.

Sample: 100 mg of the powder obtained in Identification test A

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.

2.3 C.

Sample: 100 mg of the powder obtained in Identification test A

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.

2.4 D.

Sample solution: Use the solution from Identification test C.

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

Guard against accidental inhalation of the fine powder.

Sample solution: Transfer an equivalent to 80 mg of busulfan, from finely powdered Tablets (NLT 40), to a 100-mL beaker. Extract with four 20-mL portions of acetone, each time stirring the mixture well. Allow the insoluble matter to settle, and decant the supernatant through a sintered-glass filter into a 250-mL conical flask. Evaporate the combined acetone extracts to about 10 mL, add phenolphthalein TS, and neutralize with 0.05 N sodium hydroxide. Evaporate to dryness, and add about 30 mL of water. 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 the labeled amount of busulfan (C₆H₁₄O₆S₂).

Acceptance criteria: 93.0%-107.0%

4 PERFORMANCE TESTS

DISINTEGRATION (701)

Time: 30 min, the use of disks being omitted

Acceptance criteria: Meet the requirements

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.