- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Allopurinol Oral Suspension |
Note: Allopurinol Oral Suspension is not currently licensed in the United Kingdom.
Xanthine oxidase inhibitor; treatment of gout and hyperuricaemia.
Allopurinol Oral Suspension is a suspension of Allopurinol in a suitable flavoured vehicle.
The oral suspension complies with the requirements stated under Oral Liquids, the requirements stated under Unlicensed Medicines and with the following requirements.
95.0 to 105.0% of the stated amount.
A. The light absorption, Appendix II B, in the range 230 to 350 nm of solution (2) obtained in the Assay is concordant with that of solution (3).
B. In the Assay, the principal peak in the chromatogram obtained with solution (2) has the same retention time as that in the chromatogram obtained with solution (3).
pH, 2.5 to 4.5, Appendix V L.
Complies with the requirements stated under Unlicensed Medicines, Oral Suspensions, using 900 mL of 0.01m hydrochloric acid as the dissolution medium and rotating the paddle at 75 revolutions per minute. Use a volume of the oral suspension containing one dose.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) 0.92% w/v solution of sulfanilamide in methanol (internal standard solution).
(2) To a quantity of the oral suspension containing 0.1 g of Allopurinol add 30 mL of a solution containing 10% w/v of sodium chloride in 0.1m sodium hydroxide. Add 10 mL of the internal standard solution and sufficient methanol to produce 100 mL; mix and filter through glass wool. Dilute 25 volumes of the resulting solution to 100 volumes with a 1% w/v solution of anhydrous potassium dihydrogen orthophosphate, mix and filter through a 0.45-µm membrane filter.
(3) Dissolve 0.1 g of allopurinol BPCRS in 30 mL of a solution containing 10% w/v of sodium chloride in 0.1m sodium hydroxide. Add 10 mL of the internal standard solution and sufficient methanol to produce 100 mL; mix. Dilute 25 mL of the resulting solution to 100 mL with a 1% w/v solution of anhydrous potassium dihydrogen orthophosphate, mix and filter through a 0.45-µm membrane filter.
(4) Dilute 10 volumes of solution (3) to 100 volumes with the mobile phase; further dilute 10 volumes to 100 volumes and then 5 volumes to 100 volumes with the mobile phase; mix and filter through a 0.45-µm membrane filter.
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Develosil RP-aqueous is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 250 nm.
(f) Inject 10 µL of each solution.
2 volumes of methanol and 98 volumes of a 2% w/v solution of anhydrous potassium dihydrogen orthophosphate.
The chromatogram obtained with solution (3) shows a peak due to allopurinol (retention time about 11 minutes) and a peak with a retention relative to allopurinol of about 0.5 (sulfanilamide).
Using the chromatogram obtained with solution (4), calculate the ratio of the area of the peak due to allopurinol to the area of the peak due to the internal standard (R).
In the chromatogram obtained with solution (2):
the ratio of the area of any secondary peak to the area of the peak due to the internal standard is not greater than 0.04R (0.2%).
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) 0.92% w/v solution of sulfanilamide in methanol (internal standard solution).
(2) To a weighed quantity of the oral suspension containing 0.1 g of Allopurinol add 30 mL of a solution containing 10% w/v of sodium chloride in 0.1m sodium hydroxide. Add 10 mL of the internal standard solution and sufficient methanol to produce 100 mL; mix and filter through glass wool. Dilute 25 volumes of the resulting solution to 100 volumes with a 1% w/v solution of anhydrous potassium dihydrogen orthophosphate, mix and filter through a 0.45-µm membrane filter.
(3) Dissolve 0.1 g of allopurinol BPCRS in 30 mL of a solution containing 10% w/v of sodium chloride in 0.1m sodium hydroxide. Add 10 mL of the internal standard solution and sufficient methanol to produce 100 mL; mix. Dilute 25 volumes of the resulting solution to 100 volumes with a 1% w/v solution of anhydrous potassium dihydrogen orthophosphate, mix and filter through a 0.45-µm membrane filter.
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Develosil RP-aqueous is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 250 nm.
(f) Inject 10 µL of each solution.
2 volumes of methanol and 98 volumes of a 2% w/v solution of anhydrous potassium dihydrogen orthophosphate.
Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C5H4N4O, weight in volume, using the declared content of C5H4N4O in allopurinol BPCRS.
The impurities limited by the requirements of this monograph include impurities A, B, C, D and E listed under Allopurinol.