Furosemide Injection

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

Furosemide Injection is a sterile solution of Furosemide in Water for Injection prepared with the aid of Sodium Hydroxide or, where intended solely for veterinary use, Diethanolamine or Monoethanolamine. It contains NLT 90.0% and NMT 110.0% of the labeled amount of furosemide (C₁₂H₁₁ClN₂O₅S).

2 IDENTIFICATION

A.

Standard stock solution: 0.4 mg/mL of USP Furosemide RS, prepared as follows. Transfer about 10 mg of USP Furosemide RS to a 25-mL volumetric ask. Add 6.0 mL of 0.1 N sodium hydroxide and dissolve. Dilute with water to volume.

Standard solution: 8 μg/mL of USP Furosemide RS from Standard stock solution in 0.02 N sodium hydroxide

Sample stock solution: Nominally 0.4 mg/mL of furosemide in water, prepared as follows. Transfer a volume of Injection, nominally equivalent to 40 mg of furosemide, to a 100-mL volumetric ask and dilute with water to volume.

Sample solution: Nominally 8 μg/mL of furosemide from Sample stock solution in 0.02 N sodium hydroxide

Analysis: Concomitantly determine the UV absorption spectra of Standard solution and Sample solution.

Acceptance criteria: The UV absorption spectra of Standard solution and Sample solution exhibit maxima and minima at the same wavelengths.

3 ASSAY

[Note—Protect furosemide solutions from exposure to light.]

Procedure

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

Solution A: Acetonitrile and water (50:50)

Diluent: Transfer 22 mL of glacial acetic acid to a suitable container and dilute with Solution A to 1000 mL.

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: 1.0 mg/mL of USP Furosemide RS in Diluent

Sample solution: Nominally 1.0 mg/mL of furosemide in Diluent, prepared as follows. Transfer a volume of Injection, nominally equivalent to 10 mg of furosemide, to a 10-mL volumetric ask and dilute with Diluent to volume.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm for furosemide 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.]

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

3.2 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

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of furosemide (C₁₂H₁₁ClN₂O₅S) in the portion of Injection taken:

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

r_U = peak response of furosemide from the Sample solution at 254 nm

r_S = peak response of furosemide from the Standard solution at 254 nm

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Limit of Furosemide Related Compound B

[Note—Protect furosemide solutions from exposure to light.]

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

Standard solution: 0.01 mg/mL of USP Furosemide Related Compound B RS in Diluent

Analysis

Samples: Standard solution and Sample solution

Compare the peak responses of furosemide related compound B obtained between the Standard solution and Sample solution. Acceptance criteria: NMT 1.0% (the peak response at 254 nm of furosemide related compound B from the Sample solution is NMT that from the Standard solution)

Where the Injection is labeled as intended solely for veterinary use: NMT 2.5% (the peak response at 254 nm of furosemide related compound B from the Sample solution is NMT 2.5 times that from the Standard solution)

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: It contains NMT 3.6 USP Endotoxin Units/mg of furosemide.

pH 〈791〉: 8.0–9.3

Where the Injection is labeled as intended solely for veterinary use, and it contains diethanolamine: 7.0–7.8

Where the Injection is labeled as intended solely for veterinary use, and it contains monoethanolamine: 8.0–9.3

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections.

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Store in single-dose or multiple-dose, light-resistant containers,preferably (RB 1-Apr-2023) of Type I glass.

Labeling: Injection intended solely for veterinary use is so labeled.

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