Action and use
Cytotoxic alkylating agent.
Definition
Busulfan Tablets contain Busulfan. They are coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of busulfan, C6H14O6S2
90.0 to 115.0% of the stated amount.
Identification
A. Shake a quantity of the powdered tablets containing 10 mg of Busulfan with 10 mL of hot
acetone, filter and evaporate the filtrate to dryness. Dry the residue at 60° at a pressure not exceeding 0.7 kPa for 1 hour. The
infrared absorption spectrum of the residue,
Appendix II A, is concordant with the
reference spectrum of busulfan
(RS 035).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (3) is similar to that of the principal peak in the chromatogram obtained with solution (1).
TESTS
Disintegration
Maximum time, 15 minutes, Appendix XII A1.
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Busulfan comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for gas chromatography, Appendix III B, using the following solutions. Prepare a 0.0001% w/v solution of 1,5-di-iodopentane (internal standard) in acetone (solution A).
(1) Add 5 mL of a 30% w/v solution of
sodium iodide in
acetone to 5 mL of a 0.0001% w/v solution of
busulfan BPCRS in
acetone, stopper the flask lightly and heat in a water bath at 50° for 90 minutes. Cool, add 10 mL of solution A, mix, add 10 mL of
water and 20 mL of
hexane, shake vigorously for 1 minute and allow to separate. Use the hexane layer.
(2) Prepare solution (2) in the same manner as solution (3) but using 10 mL of
acetone in place of solution A.
(3) Add 1 mL of
water to one tablet in a 50 mL graduated flask and mix with the aid of ultrasound until completely dispersed. Add 30 mL of
acetone, shake for 15 minutes and dilute to 50 mL with
acetone. Centrifuge and dilute a quantity of the supernatant liquid with
acetone to produce a solution containing 0.0001% w/v of Busulfan. To 5 mL of the resulting solution add 5 mL of a 30% w/v solution of
sodium iodide in
acetone, stopper the flask lightly and heat in a water bath at 50° for 90 minutes. Cool, add 10 mL of solution A, mix, add 10 mL of
water and 20 mL of
hexane, shake vigorously for 1 minute and allow to separate. Use the hexane layer.
chromatographic conditions
(a) Use a glass column (1.5 m × 4 mm) packed with
acid-washed, diatomaceous support (80 to 100 mesh) coated with 3% w/w of phenyl methyl silicone fluid (50% phenyl) (OV-17 is suitable).
(b) Use
helium as the carrier gas at 1.7 mL per minute.
(c) Use isothermal conditions maintained at 140°.
(d) Use an inlet temperature of 160°.
(e) Use an electron capture detector.
(f) Inject 1 µL of each solution.
determination of content
Calculate the content of C6H14O6S2 using the declared content of C6H14O6S2 in busulfan BPCRS.
Assay
Weigh and powder 20 tablets. Carry out the method for gas chromatography, Appendix III B, using the following solutions. Prepare a 0.0001% w/v solution of 1,5-di-iodopentane (internal standard) in acetone (solution A).
(1) Add 5 mL of a 30% w/v solution of
sodium iodide in
acetone to 5 mL of a 0.0001% w/v solution of
busulfan BPCRS in
acetone, stopper the flask lightly and heat in a water bath at 50° for 90 minutes. Cool, add 10 mL of solution A, mix, add 10 mL of
water and 20 mL of
hexane, shake vigorously for 1 minute and allow to separate. Use the hexane layer.
(2) Prepare solution (2) in the same manner as solution (3) but using 10 mL of
acetone in place of solution A.
(3) Add 5 mL of
water to a quantity of powdered tablets containing 2.5 mg of Busulfan and mix with the aid of ultrasound until completely dispersed. Add 150 mL of
acetone, shake for 15 minutes and dilute to 250 mL with
acetone. Centrifuge and dilute 10 mL of the supernatant liquid to 100 mL with
acetone. To 5 mL of the resulting solution add 5 mL of a 30% w/v solution of
sodium iodide in
acetone, stopper the flask lightly and heat in a water bath at 50° for 90 minutes. Cool, add 10 mL of solution A, mix, add 10 mL of
water and 20 mL of
hexane, shake vigorously for 1 minute and allow to separate. Use the hexane layer.
chromatographic conditions
The chromatographic conditions described under Uniformity of content may be used.
determination of content
Calculate the content of C6H14O6S2 using the declared content of C6H14O6S2 in busulfan BPCRS.