Probenecid Tablets

General Notices

Action and use

Uricosuric drug.

Definition

Probenecid Tablets contain Probenecid.

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

Content of probenecid, C₁₃H₁₉NO₄S

95.0 to 105.0% of the stated amount.

Identification

A. Triturate a quantity of the powdered tablets containing 0.5 g of Probenecid with ethanol (96%), filter, concentrate the filtrate by evaporation on a water bath, cool, filter and recrystallise the residue from ethanol (50%). The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of probenecid (RS 287).

B. The light absorption of the final solution obtained in the Assay, Appendix II B, exhibits maxima at 225 nm and 248 nm.

C. Melting point of the residue obtained in test A, about 199°, Appendix V A.

Tests

Disintegration

Maximum time, 30 minutes, Appendix XII A1.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel GF₂₅₄ as the coating substance and a mixture of 10 volumes of glacial acetic acid, 15 volumes of chloroform, 20 volumes of di-isopropyl ether and 55 volumes of toluene as the mobile phase. Apply separately to the plate 20 µL of each of the following solutions. For solution (1) extract a quantity of the powdered tablets containing 0.2 g of Probenecid with 20 mL of acetone, filter and use the filtrate. For solution (2) dilute 1 volume of solution (1) to 200 volumes with acetone. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%).

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Rotate the paddle at 50 revolutions per minute and use as the medium 900 mL of a phosphate buffer prepared in the following manner. Dissolve 6.8 g of potassium dihydrogen orthophosphate in 250 mL of water, add 190 mL of 0.2m sodium hydroxide and 400 mL of water, adjust the pH to 7.5 with 0.2m sodium hydroxide and add sufficient water to produce 1000 mL. Withdraw a sample of 10 mL of the medium, filter and dilute 4 mL of the filtrate to 100 mL with 0.1m sodium hydroxide. Measure the absorbance of this solution, Appendix II B, at 244 nm using in the reference cell a solution prepared by diluting 4 mL of the phosphate buffer to 100 mL with 0.1m sodium hydroxide. Calculate the total content of C₁₃H₁₉NO₄S in the medium taking 359 as the value of A(1%, 1 cm) at the maximum at 244 nm.

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing 0.2 g of Probenecid add 200 mL of ethanol (96%) and 5 mL of 1m hydrochloric acid, heat on a water bath at 70° for 30 minutes, shaking occasionally, cool, add sufficient ethanol (96%) to produce 250 mL and filter. To 5 mL of the filtrate add 5 mL of 0.1m hydrochloric acid, dilute to 250 mL with ethanol (96%) and measure the absorbance of the resulting solution at the maximum at 248 nm, Appendix II B. Calculate the content of C₁₃H₁₉NO₄S taking 332 as the value of A(1%, 1 cm) at the maximum at 248 nm.