C6H9N3O3 171.15

1H-Imidazole-1-ethanol, 2-methyl-5-nitro-.
2-Methyl-5-nitroimidazole-1-ethanol [443-48-1].

Packaging and storage— Preserve in well-closed, light-resistant containers. Store at 25, excursions permitted between 15 and 30.

USP Reference standards 11— USP Metronidazole RS.

Identification—

Melting range 741: between 159 and 163.

Loss on drying 731— Dry it at 105 for 2 hours: it loses not more than 0.5% of its weight.

Residue on ignition 281: not more than 0.1%.

Heavy metals, Method II 231: 0.005%.

Non-basic substances— A 1-g portion dissolves completely in 10 mL of dilute hydrochloric acid (1 in 2).

Chromatographic purity— Dissolve 100 mg of Metronidazole in 10.0 mL of acetone. Similarly prepare a Standard solution of USP Metronidazole RS in acetone having a concentration of 3.0 mg per mL. Dilute an aliquot of this Standard solution quantitatively and stepwise with acetone to obtain a solution having a concentration of 30 µg per mL (diluted Standard solution). Apply separately 20-µL portions of the test solution, the Standard solution, and the diluted Standard solution to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of chloroform, dehydrated alcohol, diethylamine, and water (80:10:10:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate. Spray the plate with titanium trichloride (20% solution), heat at 110 until the blue-gray color begins to disappear, and cool the plate. [Caution—Use fast blue B salt spray with adequate ventilation, avoid inhalation of vapors, and avoid contact with the skin ] Spray the plate with fast blue B salt solution (1 in 100), allow to stand for 3 minutes, and spray with a mixture of alcohol, water, and ammonium hydroxide (50:30:20): the RF value of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution, and no spot, other than the principal spot, obtained from the test solution is larger or more intense than the principal spot obtained from the diluted Standard solution.

Residual solvents 467: meets the requirements.

Assay— Dissolve about 100 mg of Metronidazole, accurately weighed, in 20 mL of acetic anhydride, warming slightly to effect solution. Cool, add 1 drop of malachite green TS, and titrate with 0.1 N perchloric acid VS from a 10-mL microburet to a yellow-green endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 17.12 mg of C6H9N3O3.

Expert Committee : (MDAA05) Monograph Development-Antivirals and Antimicrobials

USP29–NF24 Page 1425

Phone Number : 1-301-816-8394