Bumetanide 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

Bumetanide Injection is a sterile solution of bumetanide in Water for Injection. ▲It may contain buffering agents, preservatives, and isotonicity agents.▲ (USP 1-May-2024) It contains NLT 90.0% and NMT 110.0% of the labeled amount of bumetanide (C₁₇H₂₀N₂O₅S).

2 IDENTIFICATION

A. ▲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)

B. ▲The UV spectrum of the bumetanide peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the corresponding peak of the Standard solution, as obtained in the Assay.▲ (USP 1-May-2024)

3 ASSAY

Procedure

Solution A: 0.5% (v/v) formic acid in water (add 5 mL of formic acid to a 1-L volumetric flask, 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 solution: Nominally 0.1 mg/mL of bumetanide prepared as follows. Transfer a suitable amount of Injection to a suitable volumetric flask. Add methanol to about 40% of the total volume and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 200–400 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 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of bumetanide (C₁₇H₂₀N₂O₅S) in the portion of Injection 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 = nominal concentration of bumetanide in the Sample solution (mg/mL)

▲ (USP 1-May-2024)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

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, and USP Bumetanide Related Compound B RS individually prepared as follows. Transfer suitable amounts each of USP Bumetanide RS, USP Bumetanide Related Compound A RS, and USP Bumetanide Related Compound B RS 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.

System suitability solution: 0.25 µg/mL each of USP Bumetanide RS, USP Bumetanide Related Compound A RS, and USP Bumetanide Related Compound B RS from the corresponding Standard stock solutions in Diluent

Standard solution: 0.25 µg/mL each of USP Bumetanide RS and USP Bumetanide Related Compound A RS from the corresponding Standard stock solutions in Diluent

Sensitivity solution: 0.125 µg/mL each of USP Bumetanide RS and USP Bumetanide Related Compound A RS from the Standard solution in Diluent

Sample solution: Nominally 0.25 mg/mL of Bumetanide from Injection

Chromatographic system:

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

Injection volume: 50 µL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

[Note—The relative retention time for bumetanide related compound B with respect to bumetanide is 0.7.]

Resolution: NLT 20 between bumetanide related compound A and bumetanide related compound B, System suitability 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 bumetanide related compound A in the portion of Injection taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

where

rᵤ = peak response of bumetanide related compound A from the Sample solution

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

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

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

Calculate the percentage of any unspecified impurity in the portion of Injection 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 = nominal concentration of bumetanide in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

ᵃ Bumetanide related compound A is not included in the total impurities.

▲ (USP 1-May-2024)

5 SPECIFIC TESTS

Change to read:

Bacterial Endotoxins Test 〈85〉: ▲Meets the requirements▲ (USP 1-May-2024)

pH 〈791〉: 6.8–7.8

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light. ▲Store at controlled room temperature.▲ (USP 1-May-2024)

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 1-May-2024)