Metronidazole Benzoate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₃H₁₃N₃O₄               275.26

2-(2-Methyl-5-nitroimidazol-1-yl)ethyl benzoate CAS RN^®: 13182-89-3; UNII: A355C835XC.

1 DEFINITION

Metronidazole Benzoate contains NLT 98.5% and NMT 101.0% of metronidazole benzoate (C₁₃H₁₃N₃O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{▲(CN 1-MAY-2020)}

B. The principal spot of the Sample solution corresponds to that of Standard solution A, as obtained in the test for Organic Impurities.

3 ASSAY

PROCEDURE

Sample solution: Dissolve with stirring 250 mg of Metronidazole Benzoate in 50.0 mL of glacial acetic acid.

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Titrant: 0.1 N perchloric acid

Endpoint detection: Potentiometric

Analysis: Titrate the Sample solution with Titrant. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 27.53 mg of 13 13 (C₁₃H₁₃N₃O₄).

Acceptance criteria: 98.5%-101.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Standard solution A: 0.1 mg/mL of USP Metronidazole Benzoate RS in acetone

Standard solution B: 0.04 mg/mL of USP Metronidazole Benzoate RS in acetone from Standard solution A

Standard solution C: 0.2 mg/mL each of USP Metronidazole RS and USP Tinidazole Related Compound A RS in acetone

Sample solution: 20 mg/mL of Metronidazole Benzoate in acetone

Chromatographic system

(See Chromatography (621), Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.2-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Ethyl acetate

System suitability

Sample: Standard solution C

Suitability requirements: The test is valid only if the metronidazole and tinidazole related compound A spots are clearly separated.

Analysis

Samples: Standard solution A, Standard solution B, Standard solution C, and Sample solution

Proceed as directed in the chapter. Examine the plate under short-wavelength UV light.

Acceptance criteria: No secondary spot of the Sample solution is larger or more intense than the principal spot of Standard solution A (0.5%); and NMT three spots, excluding the principal spot, of the Sample solution are larger or more intense than the principal spot of Standard solution B (0.2%).

5 SPECIFIC TESTS

5.1 ACIDITY

Sample: 2.0 g

Analysis: Neutralize 40 mL of a mixture of dimethylformamide and water (1:1) with hydrochloric acid or 0.02 M sodium hydroxide. Add 0.2 mL of methyl red TS and the Sample, mix to dissolve, and titrate with 0.02 M sodium hydroxide.

Acceptance criteria: NMT 0.25 mL is required to produce a color change.

5.2 LOSS ON DRYING (731)

Analysis: Dry at 80° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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

USP Metronidazole Benzoate RS

USP Tinidazole Related Compound A RS

2-Methyl-5-nitroimidazole.

C₄H₅N₃O₂            127.10