Metronidazole Tablets

General Notices

Action and use

Imidazole antibacterial.

Definition

Metronidazole Tablets contain Metronidazole.

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

Content of metronidazole, C₆H₉N₃O₃

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 0.1 g of Metronidazole with 40 mL of chloroform for 15 minutes, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of metronidazole (RS 229).

B. Shake a quantity of the powdered tablets containing 0.2 g of Metronidazole with 4 mL of 0.5m sulfuric acid and filter. To the filtrate add 10 mL of picric acid solution R1 and allow to stand. The melting point of the precipitate, after washing with water and drying at 105°, is about 150°, Appendix V A.

C. Heat a quantity of the powdered tablets containing 10 mg of Metronidazole on a water bath with 10 mg of zinc powder, 1 mL of water and 0.25 mL of hydrochloric acid for 5 minutes, cool in ice, add 0.5 mL of sodium nitrite solution and remove the excess of nitrite with sulfamic acid. Add 0.5 mL of 2-naphthol solution and 2 mL of 5m sodium hydroxide. An orange-red colour is produced.

TEST

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.00050% w/v of 2-methyl-5-nitroimidazole BPCRS in the mobile phase. For solution (2) shake a quantity of the powdered tablets containing 0.2 g of Metronidazole with 100 mL of the mobile phase for 5 minutes, dilute to 200 mL with the mobile phase, filter and use the filtrate. Solution (3) contains 0.00050% w/v of 2-methyl-5-nitroimidazole BPCRS in solution (2).

The chromatographic procedure may be carried out using (a) a stainless steel column (20 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (10 µm) (Spherisorb ODS 1 is suitable), (b) a mixture of 30 volumes of methanol and 70 volumes of 0.01m potassium dihydrogen orthophosphate as the mobile phase with a flow rate of 1 mL per minute and (c) a detection wavelength of 315 nm. Record the chromatograms for 3 times the retention time of the principal peak in the chromatogram obtained with solution (2).

Adjust the sensitivity so that the height of the peak due to 2-methyl-5-nitroimidazole in the chromatogram obtained with solution (3) is about 50% of full-scale deflection. Measure the height (a) of the peak due to 2-methyl-5-nitroimidazole and the height (b) of the lowest part of the curve separating this peak from the principal peak. The test is not valid unless a is greater than 10b.

The area of any secondary peak in the chromatogram obtained with solution (2) is not greater than the area of the peak due to 2-methyl-5-nitroimidazole in the chromatogram obtained with solution (1).

Assay

Weigh and powder 20 tablets. Transfer a quantity of the powder containing 0.2 g of Metronidazole to a sintered-glass crucible and extract with six 10 mL quantities of hot acetone. Cool, add to the combined extracts 50 mL of acetic anhydride and 0.1 mL of a 1% w/v solution of brilliant green in anhydrous acetic acid and titrate with 0.1m perchloric acid VS to a yellowish-green end point. Repeat the operation without the powdered tablets. The difference between the titrations represents the amount of perchloric acid required. Each mL of 0.1m perchloric acid VS is equivalent to 17.12 mg of C₆H₉N₃O₃.