Furosemide Oral Solution

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 Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of furosemide (C₁₂H₁₁ClN₂O₅S).

2 IDENTIFICATION

Delete the following:

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Standard solution: 6 µg/mL of USP Furosemide RS in 0.01 N sodium hydroxide

Sample solution: Nominally 6 µg/mL of furosemide from the Oral Solution in 0.01 N sodium hydroxide

Acceptance criteria: Absorptivities are not significantly different. _{(USP 1-May-2022)}

Add the following:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. _{(USP 1- May-2022)}

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

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Procedure

[Note—Protect sample specimens, the USP Reference Standards, and solutions containing them by conducting the analysis without delay, under subdued light, or using low-actinic glassware.]

Mobile phase: Acetonitrile, glacial acetic acid, and water (35:2:165)

Diluent: Acetonitrile, glacial acetic acid, and water (22:1:22)

System suitability solution: 0.1 mg/mL each of USP Furosemide RS and USP Furosemide Related Compound A RS in Diluent _{(USP 1-May 2022)}

Standard solution: 1 mg/mL of USP Furosemide RS in Diluent

Sample solution: Nominally 1 mg/mL of furosemide from the Oral Solution in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification A, use a diode array detector in the range of 200–400 nm. (USP 1-May-2022) Column: 4.6-mm × 25-cm; 5-μm (USP 1-May-2022) packing L10

Flow rate: 2 mL/min

Injection volume: 10 µL

Run time: NLT 1.9 times the retention time of furosemide (USP 1-May-2022)

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for furosemide and furosemide related compound A are about 1.0 and 1.1, respectively. _{(USP 1-May 2022)} ]

Suitability requirements

Resolution: NLT 1.5 between furosemide and furosemide related compound A, System suitability solution Tailing factor: NMT 1.5, Standard solution _{(USP 1-May-2022)}

Relative standard deviation: NMT 1.0%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of furosemide (C₁₂H₁₁ClN₂O₅S) in the portion of the Oral Solution taken: 

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

r_U = peak response of furosemide in the Sample solution

r_S = peak response of furosemide in the Standard solution

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 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉

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

Delete the following:

Minimum Fill 〈755〉: Meets the requirements _{(USP 1-May-2022)}

Deliverable Volume 〈698〉

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

5 IMPURITIES

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Limit of Furosemide Related Compound B

[Note—Protect sample specimens, the USP Reference Standards, and solutions containing them by conducting the analysis without delay, under subdued light, or using low-actinic glassware.]

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

Standard solution:  (USP 1-May-2022) 15.0 µg/mL of USP Furosemide Related Compound B RS in Diluent

Sensitivity solution: 1.5 µg/mL of USP Furosemide Related Compound B RS from the Standard solution in Diluent _{(USP 1-May-2022)}

Sample solution: Nominally 1 mg/mL of furosemide from the Oral Solution in Diluent

5.1 System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution (USP 1-May-2022)

[Note—The relative retention times for furosemide and furosemide related compound A are about 1.0 and 1.1, respectively. (USP 1-May 2022) ]

Suitability requirements

Resolution: NLT 1.5 between furosemide and furosemide related compound A, System suitability solution

 (USP 1-May-2022)

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise-ratio: NLT 10, Sensitivity solution (USP 1-May-2022)

5.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of furosemide related compound B in the portion of the Oral Solution taken:

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

r_U = peak response of furosemide related compound B in the Sample solution

r_S = peak response of furosemide related compound B in the Standard solution

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

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

 (USP 1-May-2022)

Acceptance criteria: NMT 1.5% (USP 1-May-2022)

6 SPECIFIC TESTS

pH 〈791〉: 7.0–10.0

Add the following:

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 102 cfu/mL. The total yeast and mold count is NMT 101 cfu/mL. It meets the requirement of the test for absence of Escherichia coli. (USP 1-May-2022)

7 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature. (USP 1-May-2022)

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USP Reference Standards 〈11〉

USP Furosemide RS

USP Furosemide Related Compound A RS

2-Chloro-4-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acid. _{(USP 1-May-2022)}

C₁₂H₁₁ClN₂O₅S             330.74

USP Furosemide Related Compound B RS

2-Amino-4-chloro-5-sulfamoylbenzoic acid. _{(USP 1-May-2022)}

C₇H₇ClN₂O₄S                250.65