Chlorambucil Tablets

General Notices

Action and use

Cytotoxic alkylating agent.

Definition

Chlorambucil Tablets contain Chlorambucil. They are coated.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of chlorambucil, C₁₄H₁₉Cl₂NO₂

90.0 to 110.0% of the stated amount.

Identification

Shake a quantity of the powdered tablets containing 10 mg of Chlorambucil with 10 mL of 2m hydrochloric acid, allow to stand for 30 minutes, shaking occasionally, and filter. To 5 mL of the filtrate add 0.5 mL of potassium tetraiodomercurate solution; a precipitate is produced. To the remainder of the filtrate add 0.15 mL of dilute potassium permanganate solution; the colour of the permanganate is discharged.

Tests

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Chlorambucil comply with the requirements stated under Tablets using the following method of analysis.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Dissolve one tablet as completely as possible in 10 mL of 0.1m hydrochloric acid, add 40 mL of acetonitrile and mix for 5 minutes with the aid of ultrasound. Add sufficient acetonitrile to produce a solution containing 0.002% w/v of chlorambucil, filter through a glass microfibre filter (Whatman GF/C is suitable), discarding the first 20 mL of filtrate, and use the filtrate.

(2) 0.0020% w/v of chlorambucil BPCRS in a mixture of 1 volume of 0.1m hydrochloric acid and 9 volumes of acetonitrile.

chromatographic conditions

(a) Use a stainless steel column (30 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 254 nm.

(f) Inject 20 µL of each solution.

mobile phase

40 volumes of 0.02m potassium dihydrogen orthophosphate and 60 volumes of acetonitrile.

determination of content

Calculate the content of C₁₄H₁₉Cl₂NO₂ in the tablet using the declared content of C₁₄H₁₉Cl₂NO₂ in chlorambucil BPCRS.

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Dissolve as completely as possible a quantity of the powdered tablets containing 10 mg of Chlorambucil in a mixture of 25 mL of 0.1m hydrochloric acid and 100 mL of acetonitrile by mixing for 10 minutes with the aid of ultrasound. Dilute to 250 mL with acetonitrile, filter through a glass microfibre filter (Whatman GF/C is suitable), discarding the first 20 mL of filtrate, and dilute 50 mL to 100 mL with a mixture of 1 volume of 0.1m hydrochloric acid and 9 volumes of acetonitrile.