Furosemide

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

C₁₂H₁₁ClN₂O₅S          330.74

Benzoic acid, 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]-;

4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid CAS RN®: 54-31-9; UNII: 7LXU5N7ZO5.

1 DEFINITION

Furosemide contains NLT 98.0% and NMT 102.0 of furosemide (C₁₂H₁₁ClN₂O₅S), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

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

C. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Protect Furosemide solutions from exposure to light.

Mobile phase: Tetrahydrofuran, glacial acetic acid, and water (30:1:70)

Solution A: Acetonitrile and water (50:50)

Diluent: Solution A and glacial acetic acid (978:22)

System suitability solution: 20 µg/mL of USP Furosemide RS and 12 µg/mL of USP Furosemide Related Compound A RS in Diluent Standard solution: 0.2 mg/mL of USP Furosemide RS in Diluent

Sample solution: 0.2 mg/mL of Furosemide in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 272 nm. For Identification test C, use a diode-array detector in the range of 200–400 nm. Column: 4.6-mm × 25.0-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between furosemide related compound A and furosemide, System suitability solution Relative standard deviation: NMT 0.73%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of furosemide (C₁₂H₁₁ClN₂O₅S) in the portion of Furosemide 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 Furosemide RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Protect Furosemide solutions from exposure to light.

Mobile phase, Solution A, Diluent, and System suitability solution: Proceed as directed in the Assay.

Standard solution: 5.0 µg/mL each of USP Furosemide Related Compound A RS and USP Furosemide Related Compound B RS in Diluent Sample solution: 1.0 mg/mL of Furosemide in Diluent

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detectors: 254 and 272 nm

[Note—The 2,4-dichloro-5-sulfamoylbenzoic acid impurity does not respond at 272 nm, and the 2,4-bis(furfurylamino)-5-sulfamoylbenzoic acid impurity has a very intense absorbance at 254 nm. The response for furosemide is at 254 nm.]

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2.5 times the retention time of the furosemide peak

4.2 System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 2.5 between furosemide and furosemide related compound A

Relative standard deviation: NMT 2.0% for furosemide

4.3 Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The sum of the peak areas of peaks eluting before furosemide at 254 nm from the Sample solution is NMT the area of the furosemide related compound B peak at 254 nm from the Standard solution (0.5%). The sum of the peak areas of peaks eluting after furosemide at 272 nm from the Sample solution is NMT the area of the furosemide related compound A peak at 272 nm from the Standard solution (0.5%).

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 1.0%

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 Furosemide RS

USP Furosemide Related Compound A RS

2-Chloro-4-N-furfurylamino-5-sulfamoylbenzoic acid.

C₁₂H₁₁ClN₂O₅S     330.74

USP Furosemide Related Compound B RS

4-Chloro-5-sulfamoylanthranilic acid.

C₇H₇ClN₂O₄S       250.66