NOTE: This monograph has been developed to cover unlicensed formulations.
Action and use
Thiopurine cytotoxic.
DEFINITION
Mercaptopurine Oral Suspension is a suspension of Mercaptopurine Monohydrate in a suitable flavoured vehicle.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements. Where appropriate, the oral suspension also complies with the requirements stated under Unlicensed Medicines.
Content of mercaptopurine monohydrate, C5H4N4S,H2O
90.0 to 110.0% of the stated amount.
Shake the oral suspension vigorously before carrying out the following tests.
IDENTIFICATION
A. Shake a quantity of the oral suspension containing 50 mg of Mercaptopurine Monohydrate with a mixture of 20 mL of water and 0.5 mL of 5M sodium hydroxide for not more than 5 minutes, add sufficient water to produce 100 mL, mix and filter. Dilute a portion of the filtrate with sufficient 0.1M hydrochloric acid to give a final concentration of 0.0005% w/v of Mercaptopurine Monohydrate. The light absorption of the resulting solution, Appendix II B, exhibits a maximum at 325 nm.
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
TESTS
Acidity
pH, 4.0 to 6.0, Appendix V L.
Dissolution
Complies with the requirements stated under Unlicensed Medicines, Oral Suspensions, using 900 mL of 0.1M hydrochloric acid as the dissolution medium and rotating the paddle at 50 revolutions per minute. Use a volume of the oral suspension containing one dose.
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add 10 mL of a mixture of equal volumes of methanol and water to a weighed quantity of the oral suspension containing 15 mg of Mercaptopurine Monohydrate, mix with the aid of ultrasound for 15 minutes, shake for 1 hour and add sufficient of the mixture of equal volumes of methanol and water to produce 100 mL.
(2) 0.015% w/v of mercaptopurine BPCRS in methanol.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped base-deactivated octadecylsilyl silica gel for chromatography (5 μm) (Hypersil BDS 5 μm is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 328 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
10 volumes of methanol and 90 volumes of water containing 0.1% w/v of sodium heptanesulfonate monohydrate and 0.3% w/v of sulfuric acid.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C5H4N4S,H2O, weight in volume, using the declared content of C5H4N4S,H2O in mercaptopurine BPCRS.
STORAGE
Mercaptopurine Oral Suspension should be protected from light.
