Nitrofurantoin Oral Suspension

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

Nitrofurantoin Oral Suspension is a suspension of Nitrofurantoin in a suitable aqueous vehicle. It contains, in each 100 mL, NLT 460 mg and NMT 540 mg of nitrofurantoin (C₈H₆N₄O₅).

2 IDENTIFICATION

2.1 A. Infrared Absorption

Sample solution: 10 mL of Oral Suspension in 15 mL of acetone

Analysis: Warm the Sample solution to 50°, with stirring, to coagulate the excipients. Filter, evaporate the acetone with the aid of a warm air blast nearly to dryness, add 10 mL of acetic acid, heat to boiling, and filter while hot. Cool the filtrate to room temperature. Filter the precipitated nitrofurantoin, and dry at 105° for 1 h.

Acceptance criteria: The IR absorption spectrum of a Mineral oil dispersion of the precipitate obtained 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 suficient 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: 0.065 mg/mL of acetanilide in Mobile phase

Standard stock solution: 0.25 mg/mL of USP Nitrofurantoin RS prepared as follows. Transfer the required amount in suitable volumetric fiask, and dissolve in 50% of the final volume of dimethylformamide and 20% of the final volume of water. Cool to room temperature, and dilute with dimethylformamide to volume.

Standard solution: Transfer 4.0 mL of Standard stock solution to a glass-stoppered fiask, and add 15.0 mL of Internal standard solution.

Sample stock solution: Nominally 0.25 mg/mL of nitrofurantoin prepared as follows. Transfer a volume of Oral Suspension to a suitable volumetric fiask, add 20% of the final volume of water, and mix. Add 50% of the final volume of dimethylformamide, and shake the fiask for 20 min. Cool to room temperature, and dilute with dimethylformamide to volume. Centrifuge a portion of the solution, and use the supernatant to prepare the Sample solution.

Sample solution: Transfer 4.0 mL of Sample stock solution to a glass-stoppered fiask, add 15.0 mL of Internal standard solution, and mix. Pass a portion of the solution through a 5-µm pore size polytef filter, 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 its peak height is about halffifull scale.]
• Mode: LC
• Detector: UV 254 nm
• Column: 3.9-mm × 30-cm; packing L1
• Flow rate: 1.2 mL/min
• Injection size: 15 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Resolution: NLT 3.5 between the acetanilide and nitrofurantoin peaks
• Relative standard deviation: NMT 2.0% determined from the ratio of the peak responses

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity per volume, in mg/100 mL, of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) in the Oral Suspension taken:

Result = (Rᵤ/Rₛ) × Cₛ × D

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)

D = dilution factor, Sample stock solution to Sample solution, 9500

Acceptance criteria: 460–540 mg/100 mL of C₈H₆N₄O₅

4 PERFORMANCE TESTS

4.1 Uniformity of Dosage Units 〈905〉

For Oral Suspension packaged in single-unit containers: Meets the requirements

4.2 Deliverable Volume 〈698〉

For Oral Suspension packaged in multiple-unit containers: Meets the requirements

5 IMPURITIES

5.1 Limit of N-(Aminocarbonyl)-N-[([5-Nitro-2-Furanyl]Methylene)-Amino]Glycine (NF 250)

Buffer and Mobile phase: Prepare as directed in the Assay.

Standard solution: 2.5 µg/mL of USP Nitrofurantoin Related Compound A RS in Mobile phase

Sample solution: Nominally 0.05 mg/mL of nitrofurantoin in Mobile phase from Oral Suspension. Centrifuge a portion of this solution. Pass a portion of the supernatant through a polytef filter having a 5-µm pore size, discarding the first few mL.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• [Note-Adjust the operating parameters so that the NF 250 peak has a retention time of between 3 and 6 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: 1.2 mL/min
• Injection size: 30–60 µL

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The height of any peak appearing in 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 5.0%).

6 SPECIFIC TESTS

pH 〈791〉: 4.5–6.5

7 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Nitrofurantoin RS

USP Nitrofurantoin Related Compound A RS

(N-(Aminocarbonyl)-N-[([5-nitro-2-furanyl]-methylene)-amino]glycine).