Nitrofurantoin Tablets

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Nitrofurantoin Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of nitrofurantoin (C₈H₆N₄O₅).

2 IDENTIFICATION

Change to read:

2.1 A. Spectroscopic Identification Tests 〈197M〉, Infrared Spectroscopy

Sample: Add 10 mL of 6 N acetic acid to an amount equivalent to 100 mg of nitrofurantoin from powdered Tablets. Boil for a few min, and filter while hot. Cool to room temperature, collect the precipitate of nitrofurantoin, and dry at 105° for 1 h.

Acceptance criteria: The IR absorption spectrum of a Mineral oil dispersion of the precipitate from the Sample exhibits maxima only at the same wavelengths as that of a similar preparation of USP Nitrofurantoin RS.

2.2 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

3.1 Procedure

Buffer: Dissolve 6.8 g of monobasic potassium phosphate in 500 mL of water. Add about 30 mL of 1.0 N sodium hydroxide sufficient to adjust to a pH of 7.0, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (12:88)

Internal standard solution: 1 mg/mL of acetanilide in water

Standard solution: 0.56 mg/mL of USP Nitrofurantoin RS prepared as follows. Dissolve 50 mg of USP Nitrofurantoin RS in 40.0 mL of dimethylformamide, and add 50.0 mL of Internal standard solution.

Sample solution: Nominally 0.56 mg/mL of nitrofurantoin prepared as follows. Mix an amount equivalent to 50 mg of nitrofurantoin from powdered Tablets (NLT 20) with 40.0 mL of dimethylformamide, and shake mechanically for 15 min. Add 50.0 mL of Internal standard solution, mix, and cool to room temperature. Pass a portion of the solution through a nylon filter having a pore size of 0.45-µm, discarding the first few mL of the filtrate.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• [Note-Adjust the operating parameters so that the retention time of the nitrofurantoin peak is about 8 min and the peak height is about half full-scale.]
• Mode: LC
• Detector: UV 254 nm
• Column: 3.9-mm × 30-cm; packing L1
• Injection size: 5–10 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Resolution: NLT 3.0 between acetanilide and nitrofurantoin
• Relative standard deviation: NMT 2.0% determined from the ratio of the peak responses

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) in the portion of powdered Tablets taken:

Result = (Rᵤ/Rₛ) × (Cₛ/Cᵤ) × 100

Rᵤ = internal standard ratio (peak response of nitrofurantoin/peak response of acetanilide) from the Sample solution

Rₛ = internal standard ratio (peak response of nitrofurantoin/peak response of acetanilide) from the Standard solution

Cₛ = concentration of USP Nitrofurantoin RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of nitrofurantoin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: pH 7.2 phosphate buffer (see Reagents, Indicators, and Solutions—Buffer Solutions); 900 mL

Apparatus 1: 100 rpm

Times: 60 and 120 min

Standard stock solution: 0.1 mg/mL of USP Nitrofurantoin RS prepared as follows. Dissolve the required amount of USP Nitrofurantoin RS in 5% of the final volume of dimethylformamide. Dilute to final volume with Medium.

Standard solution: 10 µg/mL of USP Nitrofurantoin RS in Medium from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.

Analysis

Samples: Standard solution and Sample solution

Analytical wavelength: 375 nm

Blank: Medium

Calculate the percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved:

Result = (Aᵤ/Aₛ) × (Cₛ/L) × V × 100

Aᵤ = absorbance from the Sample solution

Aₛ = absorbance from the Standard solution

Cₛ = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 25% (Q) of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) is dissolved in 60 min, and NLT 85% (Q) of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) is dissolved in 120 min.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 IMPURITIES

5.1 Limit of Nitrofurazone

Buffer: Proceed as directed in the Assay.

Mobile phase: Tetrahydrofuran and Buffer (10:90)

System suitability stock solution: 5.0 µg/mL each of USP Nitrofurazone RS and USP Nitrofurantoin RS in dimethylformamide

System suitability solution: 0.5 µg/mL each of USP Nitrofurazone RS and USP Nitrofurantoin RS in Mobile phase from System suitability stock solution

Standard stock solution: 5.0 µg/mL of USP Nitrofurazone RS in dimethylformamide.

Standard solution: Transfer 2.0 mL of the Standard stock solution into a glass-stoppered flask, and add 20.0 mL of water.

Sample solution: Transfer an equivalent to 100 mg of nitrofurantoin from powdered Tablets into a 25-mL, glass-stoppered flask. Add 2.0 mL of dimethylformamide, and shake for 5 min. Add 20.0 mL of water, mix, and allow to stand for 15 min. Pass a portion of the mixture through a nylon filter of 0.45-µm pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• [Note-Adjust the operating parameters so that the nitrofurazone peak has a retention time of about 10.5 min and its height is about 0.1 full-scale.]
• Mode: LC
• Detector: UV 375 nm
• Column: 3.9-mm × 30-cm; packing L1
• Flow rate: 1.6 mL/min
• Injection size: 60–100 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 4.0 between the nitrofurantoin and nitrofurazone peaks, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The height of any peak from the Sample solution at a retention time corresponding to that of the main peak from the Standard solution is NMT the height of the main peak from the Standard solution (NMT 0.01%).

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Nitrofurantoin RS

USP Nitrofurazone RS