Azapropazone Tablets

General Notices

Action and use

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.

Definition

Azapropazone Tablets contain Azapropazone.

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

Content of azapropazone, C16H20N4O2,2H2O

95.0 to 105.0% of the stated content.

Identification

A. Shake a quantity of the powdered tablets containing 0.1 g of Azapropazone with 10 mL of methanol, filter (Whatman GF/C paper is suitable), evaporate the filtrate and dry the residue at 60° for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of anhydrous azapropazone (RS 017).
B. The light absorption, Appendix II B, in the range 210 to 350 nm of solution (1) obtained in the Assay is concordant with that of solution (2).

TEST

Related substances

Carry out the following operations in subdued light using low-actinic glassware without delay. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a mixture of 1 volume of phosphate buffer pH 4.0 and 3 volumes of methanol (solvent A). For solution (1) shake a quantity of the powdered tablets containing 0.1 g of Azapropazone with 70 mL of solvent A, dilute to 100 mL and filter. Solution (2) contains 0.00025% w/v of azapropazone impurity A BPCRS. Solution (3) contains 0.00075% w/v of azapropazone impurity C BPCRS. For solution (4) dilute 10 mL of solution (1) to 100 mL and dilute 1 mL of the resulting solution to 100 mL. Solution (5) contains 0.1% w/v of azapropazone impurity standard BPCRS. For solution (6) dilute 1 volume of solution (4) to 2 volumes.

The chromatographic procedure may be carried out using (a) 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) a mixture of 1 volume of glacial acetic acid, 36 volumes of methanol and 63 volumes of a 0.068% w/v solution of sodium butanesulfonate in water as the mobile phase with a flow rate of 2.5 mL per minute and (c) a detection wavelength of 254 nm.

Inject solution (5) and continue the chromatography for 5 times the retention time of the principal peak. The test is not valid unless the chromatogram obtained with solution (5) closely resembles the reference chromatogram. If necessary adjust the proportion of methanol in the mobile phase to give the required retention times.

In the chromatogram obtained with solution (1) the area of any peaks corresponding to azapropazone impurities A and C are not greater than the areas of the corresponding peaks in the chromatograms obtained with solutions (2) and (3) (0.25% and 0.75% respectively). The area of any other secondary peak other than any peak corresponding to azapropazone impurity B is not greater than the area of the peak in the chromatogram obtained with solution (4) (0.1%). Calculate the content of impurities A and C using the respective reference solutions and the content of any unnamed impurities using solution (4). The total content of impurities is not greater than 1%. Disregard any peak with an area less than the area of the peak in the chromatogram obtained with solution (6) (0.05%).

Assay

Carry out the following operations in subdued light using low-actinic glassware without delay. Weigh and powder 20 tablets. To a quantity of the powdered tablets containing 0.6 g of Azapropazone add 20 mL of water, shake for 30 minutes, add 60 mL of methanol, shake for 10 minutes and dilute to 100 mL with water. Centrifuge a portion of the solution at 3000 revolutions per minute for 10 minutes and filter the supernatant liquid through a 0.45-µm membrane filter. Dilute 5 mL of the filtrate to 500 mL with water and further dilute 15 mL of the resulting solution to 200 mL with water. Measure the absorbance of the resulting solution at the maximum at 253 nm, Appendix II B. Calculate the content of C16H20N4O2,2H2O, taking 1033 as the value of A(1%, 1 cm) at the maximum at 253 nm.

Storage

Azapropazone Tablets should be protected from light.