Metronidazole Capsules

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

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

Wavelength range: Between 1600 and 1000 cm^-1

Acceptance criteria: Capsule contents show maxima only at the same wavelengths as those of similarly prepared USP Metronidazole RS.

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 (1:4)

Standard solution: 0.03 mg/mL of USP Metronidazole RS in Mobile phase

Sample stock solution: Nominally 1 mg/mL of metronidazole prepared as follows. Mix the contents of Capsules (NLT 20). Transfer an amount equivalent to 100 mg of metronidazole to a 100-mL volumetric flask, add 80 mL of Mobile phase, and sonicate with intermittent shaking for 10 min. Shake for 30 min, and dilute with Mobile phase to volume. Centrifuge a portion of the solution.

Sample solution: 0.03 mg/mL of metronidazole in Mobile phase, from the Sample stock solution. Pass a portion of the solution through a nylon membrane filter of 0.45-µm or finer pore size. Discard the first 10 mL of the filtrate, and use the remainder.

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

Run time: 2 times the retention time of the metronidazole peak

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for five replicate injections

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response from the Sample solution

r_S = peak response 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: 30 min

Standard solution: 0.4 mg/mL of USP Metronidazole RS in Medium. Sonicate to dissolve if necessary.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and discard the first few mL..

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum at about 278 nm

Cell: 0.05 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

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

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

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

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

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

^▲Mobile phase and Chromatographic system: _{▲(ERR 1-Jun-2024)} Proceed as directed in the Assay.

Standard solution: 1 µg/mL of metronidazole from USP Metronidazole RS and 2 µg/mL of tinidazole related compound A from USP Tinidazole Related Compound A RS in Mobile phase

^▲Sample solution: Nominally 1 mg/mL of metronidazole prepared as follows. Mix the contents of Capsules (NLT 20). Transfer an amount equivalent to 100 mg of metronidazole to a 100-mL volumetric flask, add 80 mL of Mobile phase, and sonicate with intermittent shaking for 10 min. Shake for 30 min, and dilute with Mobile phase to volume. Centrifuge a portion of the solution. _{▲(ERR 1-Jun-2024)}

System suitability

Sample: Standard solution

[NOTE-The relative retention times for tinidazole related compound A and metronidazole are 0.75 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between tinidazole related compound A and metronidazole

Tailing factor: NMT 2.0 for metronidazole

Relative standard deviation: NMT 6.0% for both tinidazole related compound A and metronidazole

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tinidazole related compound A in the portion of Capsules 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

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

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

Calculate the percentage of any unspecified degradation product in the portion of Capsules taken:

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

r_U = peak response of any unspecified degradation product 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: See Table 1.

Table 1

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers, and 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