Azapropazone Capsules

General Notices

Action and use

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.

Definition

Azapropazone Capsules contain Azapropazone.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of azapropazone, C₁₆H₂₀N₄O₂,2H₂O

95.0 to 105.0% of the stated amount.

Identification

A. The infrared absorption spectrum of the contents of the capsules, Appendix II A, is concordant with the reference spectrum of azapropazone (RS 016).

B. In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as that in the chromatogram obtained with 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.

(1) Dissolve a quantity of the contents of the capsules as completely as possible in sufficient of a mixture of 1 volume of phosphate buffer pH 4.0 and 3 volumes of methanol to produce a solution containing 0.10% w/v of Azapropazone and filter.

(2) 0.00010% w/v of azapropazone impurity A BPCRS.

(3) 0.00025% w/v of azapropazone impurity B BPCRS.

(4) 0.00025% w/v of azapropazone impurity C BPCRS.

(5) Dilute 1 volume of solution (1) to 100 volumes with a mixture of 1 volume of phosphate buffer pH 4.0 and 3 volumes of methanol and further dilute 1 volume of this solution to 10 volumes with the same solvent mixture.

(6) Dilute 1 volume of solution (5) to 2 volumes with a mixture of 1 volume of phosphate buffer pH 4.0 and 3 volumes of methanol.

(7) 0.1% w/v of azapropazone impurity standard BPCRS.

chromatographic conditions

(a) Use a stainless steel column (30 cm × 3.9 mm) packed with octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use ambient column temperature.

(e) Use a detection wavelength of 254 nm.

(f) Inject 20 µL of each solution.

mobile phase

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.

system suitability

Inject solution (7) 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 (7) closely resembles the reference chromatogram supplied with the azapropazone impurity standard. If necessary adjust the proportion of methanol in the mobile phase to give the required retention times.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to azapropazone impurity A is not greater than the area of the corresponding peak in the chromatogram obtained with solution (2) (0.1%);

the area of any peak corresponding to azapropazone impurity B is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.25%);

the area of any peak corresponding to azapropazone impurity C is not greater than the area of the corresponding peak in the chromatogram obtained with solution (4) (0.25%);

the area of any other secondary peak is not greater than the area of the peak in the chromatogram obtained with solution (5) (0.1%).

Calculate the content of impurities A, B and C using the respective reference solutions and the content of any unnamed impurities using solution (5). The total nominal content of impurities is not greater than 0.5%.

Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (6) (0.05%).

Assay

(1) Shake a quantity of the mixed contents of 20 capsules containing 20 mg of Azapropazone with 40 mL of a mixture of 1 volume of phosphate buffer pH 4.0 and 3 volumes of methanol and add sufficient solvent A to produce 100 mL.

(2) 0.02% w/v of azapropazone BPCRS.