Bumetanide

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

Bumetanide contains NLT 98.0% and NMT 102.0% of bumetanide (C₁₇H₂₀N₂O₅S), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M ▲or 197A▲ (USP 1-May-2024)

B. ▲The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-May-2024)

Delete the following:

▲• C.▲ (USP 1-May-2024)

3 ASSAY

Change to read:

Procedure

Solution A: 0.5% (v/v) formic acid in water prepared as follows. To a 1-L volumetric flask, add 5 mL of formic acid and dilute with water to volume.

Solution B: Methanol

Mobile phase: See Table 1.

Standard stock solution: 0.2 mg/mL of USP Bumetanide RS in methanol

Standard solution: 0.1 mg/mL of USP Bumetanide RS from the Standard stock solution in water

Sample stock solution: 0.2 mg/mL of Bumetanide in methanol

Sample solution: 0.1 mg/mL of Bumetanide from the Sample stock solution in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 3.5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bumetanide (C₁₇H₂₀N₂O₅S) in the portion of Bumetanide taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

where

rᵤ = peak response of bumetanide from the Sample solution

rₛ = peak response of bumetanide from the Standard solution

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

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

▲ (USP 1-May-2024)

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

4 IMPURITIES

Change to read:

Residue on Ignition 〈281〉: NMT 0.1%▲ (USP 1-May-2024)

Change to read:

Organic Impurities

Solution A, Solution B, and Mobile phase: Prepare as directed in the Assay.

Diluent: Methanol and water (40:60)

Standard stock solutions:

0.1 mg/mL each of USP Bumetanide RS, USP Bumetanide Related Compound A RS, USP Bumetanide Related Compound B RS, and 0.005 mg/mL of USP Butyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate RS individually prepared as follows. Transfer suitable amounts each of these standards to separate suitable volumetric flasks. Add methanol to about 40% of the total volume of each flask to dissolve the solids. Dilute with water to volume.

Standard solution: 0.2 µg/mL each of USP Bumetanide RS, USP Bumetanide Related Compound A RS, USP Bumetanide Related Compound B RS, and USP Butyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate RS from the corresponding Standard stock solutions in Diluent

Sensitivity solution: 0.125 µg/mL each of USP Bumetanide RS, USP Bumetanide Related Compound A RS, USP Bumetanide Related Compound B RS, and USP Butyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate RS from the corresponding Standard stock solutions in Diluent

Sample solution: 0.2 mg/mL of Bumetanide prepared as follows. To a suitable amount of Bumetanide in a suitable volumetric flask, add methanol to about 40% of the total volume to dissolve the solids. Dilute with water to volume.

Chromatographic system:

Proceed as directed in the Assay, except for the Injection volume.

Injection volume: 50 µL

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

[Note—See Table 2 for the relative retention times.]

Resolution: NLT 20 between bumetanide related compound A and bumetanide related compound B, Standard solution

Relative standard deviation: NMT 5.0% for each peak, Standard solution

Signal-to-noise ratio: NLT 10 for each peak, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified impurity in the portion of Bumetanide taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

where

rᵤ = peak response of each specified impurity from the Sample solution

rₛ = peak response of the corresponding bumetanide related compound from the Standard solution

Cₛ = concentration of the corresponding bumetanide related compound Reference Standard in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Bumetanide taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

where

rᵤ = peak response of any unspecified impurity from the Sample solution

rₛ = peak response of bumetanide from the Standard solution

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

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

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

ᵃ Bumetanide related compound A, bumetanide related compound B, and butyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate are not included.

▲ (USP 1-May-2024)

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Sample: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Bumetanide RS

USP Bumetanide Related Compound A RS

3-Amino-4-phenoxy-5-sulfamoylbenzoic acid.

C₁₃H₁₂N₂O₄S 308.31

USP Bumetanide Related Compound B RS

3-Nitro-4-phenoxy-5-sulfamoylbenzoic acid.

C₁₃H₁₀N₂O₇S 338.29

USP Butyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate RS

C₂₁H₂₈N₂O₅S ▲420.52▲ (USP 1-May-2024)