Metronidazole Tablets

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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1 DEFINITION

Metronidazole Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of metronidazole (C₆H₉N₃O₃).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970

Sample stock solution: Equivalent to 15 mg/mL of metronidazole from powdered Tablets in dilute hydrochloric acid (1 in 100). Shake for several min, and filter.

Medium: Sulfuric acid in methanol (1 in 350)

Sample solution: 20 µg/mL of metronidazole in Medium from the Sample stock solution

Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Mobile phase: Methanol and water (20:80)

Standard solution: 0.5 mg/mL of USP Metronidazole RS in Mobile phase

Sample stock solution: Nominally 10 mg/mL of metronidazole in methanol from Tablets prepared as follows. Transfer 10 Tablets, whole or ground, to a suitable size volumetric flask. Add methanol, and shake by mechanical means for 30 min or until the Tablets are disintegrated. Dilute with methanol to volume, and allow the solution to stand until the insoluble material has settled.

Sample solution: Nominally 0.5 mg/mL of metronidazole in Mobile phase prepared from the clear supernatant of the Sample stock solution.

Filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 15-cm; packing L7

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of metronidazole (C₆H₉N₃O₃) in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of metronidazole from the Sample solution

r_S = peak response of metronidazole from the Standard solution 

C_S = concentration of USP Metronidazole RS in the Standard solution (mg/mL)

C_U = nominal concentration of metronidazole in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 60 min

Standard solution: USP Metronidazole RS in Medium

Sample solution: Filter a portion of the solution under test, and dilute with Medium to a concentration similar to that of the Standard solution.

Instrumental conditions

Mode: UV

Analytical wavelength: 278 nm

Blank: Medium

Analysis

Samples: Standard solution, Sample solution, and Blank

Calculate the percentage of the labeled amount of metronidazole (C₆H₉N₃O₃) dissolved.

                         Result = (A_U/A_S) × C_S x V x (1/L) × D × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution 

C_S = concentration of USP Metronidazole RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

D = dilution factor to prepare the Sample solution

Tolerances: NLT 85% (Q) of the labeled amount of metronidazole (C₆H₉N₃O₃) is dissolved. 3

Change to read:

4.2 UNIFORMITY OF DOSAGE UNITS (905): ▲Meet the requirements ▲(CN 1-Aug-2023)

Procedure for content uniformity

Diluent: Diluted hydrochloric acid (1 in 100)

Standard solution: 20 µg/mL of USP Metronidazole RS in Diluent

Sample stock solution: Transfer 1 Tablet to a 250-ml volumetric flask. Add about 100 mL of Diluent, and shake for 30 min. Dilute with Diluent to volume. Filter, discarding the first 15 mL of the filtrate. Nominally 200 µg/mL of metronidazole is prepared by transferring the filtrate quantitatively with the Diluent. FICH

Sample solution: 20 µg/mL of metronidazole in Diluent from Sample stock solution

Instrumental conditions

Mode: UV

Analytical wavelength: 278 nm

Cell: 1 cm

Blank: Diluent

Analysis

Samples: Standard solution, Sample solution, and Blank

Calculate the quantity, in mg, of metronidazole (C₆H₉N₃O₃) in each Tablet taken:

                         Result = (A_U/A_S) × (C_S/C_U) × L

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Metronidazole RS in the Standard solution (µg/mL)

C_U = nominal concentration of metronidazole in the Sample solution (µg/mL)

L = label claim (mg/Tablet)

^▲_{▲(CN 1-Aug-2023)}

5 IMPURITIES

ORGANIC IMPURITIES

Mobile phase: Methanol and water (20:80)

Standard solution: 0.5 µg/mL of USP Metronidazole RS and 2.5 µg/mL of USP Tinidazole Related Compound A RS in Mobile phase

Sample solution: Nominally 500 µg/mL of metronidazole prepared as follows. Transfer a suitable amount of powdered Tablets (NLT 20) to a suitable volumetric flask. Add Mobile phase equivalent to 80% of the flask size. Sonicate for 10 min. Dilute with Mobile phase to volume, and pass a portion of the solution through a suitable filter. Use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 319 nm

Column: 4.6-mm x 15-cm; 5-µm packing L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 30 µL

System suitability

Sample: Standard solution

[NOTE-See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 4.0 between metronidazole and tinidazole related compound A

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tinidazole related compound A in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of tinidazole related compound A from the Sample solution

r_S = peak response of tinidazole related compound A from the Standard solution s

C_S = concentration of USP Tinidazole Related Compound A RS in the Standard solution (µg/mL)

C_U = nominal concentration of metronidazole in the Sample solution (µg/mL)

Calculate the percentage of each impurity in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response for each impurity from the Sample solution

r_S = peak response of metronidazole from the Standard solution

C_S = concentration of USP Metronidazole RS in the Standard solution (µg/mL) S

C_U = nominal concentration of metronidazole in the Sample solution (µg/mL)

Acceptance criteria: See Table 1.

Table 1

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Metronidazole RS

USP Tinidazole Related Compound A RS

2-Methyl-5-nitroimidazole.

C₄H₅N₃O₂            127.10