Allopurinol Tablets

General Notices

Action and use

Xanthine oxidase inhibitor; treatment of gout and hyperuricaemia.

Definition

Allopurinol Tablets contain Allopurinol.

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

Content of allopurinol, C5H4N4O

92.5 to 107.5% of the stated amount.

Identification

A. The light absorption, Appendix II B, in the range 230 to 350 nm of the solution obtained in the Assay exhibits a maximum only at 250 nm.
B. Shake a quantity of the powdered tablets containing 0.1 g of Allopurinol with 5 mL of 1.25m sodium hydroxide and add 3 mL of phosphomolybdotungstic reagent and 5 mL of a 20% w/v solution of sodium carbonate. A greyish blue colour is produced.

TEST

Related substances

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

(1) Mix with the aid of ultrasound a quantity of the powdered tablets containing 0.1 g of Allopurinol with 10 mL of 0.1m sodium hydroxide for about 1 minute, immediately dilute to 200 mL with mobile phase A and filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with mobile phase A and further dilute 1 volume to 10 volumes with mobile phase A.
(3) Dissolve 10 mg of allopurinol impurity A BPCRS and 5 mg each of allopurinol impurity B BPCRS, allopurinol impurity C BPCRS, allopurinol impurity D BPCRS and allopurinol impurity E BPCRS in mobile phase A. Add 20 mL of solution (1) and immediately dilute to 100 mL with mobile phase A. Dilute 1 mL of the resulting solution to 100 mL with mobile phase A.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 5µ is suitable).
(b) Use gradient 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 230 nm.
(f) Inject 20 µL of each solution.
mobile phase
Mobile phase AA mixture of 1 volume of methanol and 9 volumes of a 0.125% w/v solution of potassium dihydrogen orthophosphate.
Mobile phase BA mixture of 3 volumes of methanol with 7 volumes of a 0.125% w/v solution of potassium dihydrogen orthophosphate.
system suitability

The test is not valid unless in solution (3) the resolution factor between the peaks corresponding to impurity A and allopurinol is at least 3.

Inject solution (3). When the chromatogram is recorded in the prescribed conditions, the retention times are: impurity A, about 4.2 minutes; impurities B and C, about 6.1 minutes; allopurinol, about 7.7 minutes; impurity D, about 26.1 minutes; impurity E, about 27.8 minutes. Inject solution (1) and solution (2). Continue the chromatography of solution (1) for 5 times the retention time of allopurinol.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity A is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.2%);

the area of any unresolved double peak corresponding to impurities B and C is not greater than the area of the corresponding double peak in the chromatogram obtained with solution (3) (0.2%);

the area of any peaks corresponding to impurity D or impurity E is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.1%);

the area of any other secondary peak is not greater than the area of the peak due to allopurinol in the chromatogram obtained with solution (2) (0.1%);

the sum of the areas of any other secondary peaks is not greater than 3 times the area of the peak due to allopurinol in the chromatogram obtained with solution (2) (0.3%).

Disregard any peak with an area less than 0.2 times that of the peak due to allopurinol in the chromatogram obtained with solution (2) (0.02%).

Assay

Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.1 g of Allopurinol with 20 mL of 0.05m sodium hydroxide for 20 minutes, add 80 mL of 0.1m hydrochloric acid, shake for 10 minutes, add sufficient 0.1m hydrochloric acid to produce 250 mL, filter and dilute 10 mL of the filtrate to 250 mL with 0.1m hydrochloric acid. Measure the absorbance of the resulting solution at the maximum at 250 nm, Appendix II B, using 0.1m hydrochloric acid in the reference cell. Calculate the content of C5H4N4O taking 563 as the value of A (1%, 1 cm) at the maximum at 250 nm.