Ethacrynate Sodium for 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

Ethacrynate Sodium for Injection is a sterile, freeze-dried powder prepared by the neutralization of Ethacrynic Acid with the aid of Sodium Hydroxide. It contains an amount of ethacrynate sodium equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of ethacrynic acid (C₁₃H₁₂Cl₂O₄).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Diluent: Acidified methanol prepared by adding 9 mL of hydrochloric acid to 100 mL of methanol

Sample solution: 50 μg/mL in Diluent

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Buffer: Mix 10 mL of triethylamine and about 900 mL of water in a 1-L volumetric flask. Adjust with phosphoric acid to a pH of 6.8 ± 0.1, and dilute with water to volume.

Diluent: Acetonitrile and water (20:30)

Mobile phase: Acetonitrile and Buffer (400:600)

Standard solution: 0.5 mg/mL of USP Ethacrynic Acid RS in Diluent

Sample stock solution: Nominally equivalent to 2.5 mg/mL of ethacrynic acid from a suitable number of containers of Ethacrynate Sodium for Injection prepared as follows. Combine the contents of a suitable number of containers of Ethacrynate Sodium for Injection, equivalent to about 500 mg of ethacrynic acid, in a 200-mL volumetric flask. Add 5 mL of Diluent to each container, mix to dissolve the contents, and combine the resulting solutions in the volumetric flask taken. Rinse each container with two additional 5-mL portions of Diluent, add the rinsings to the solution in the volumetric flask, and dilute with Diluent to volume.

Sample solution: 0.5 mg/mL of ethacrynic acid in Diluent from Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1200 theoretical plates

Tailing factor: NMT 2

Capacity factor, k′: NLT 0.8

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ethacrynic acid (C₁₃H₁₂Cl₂O₄) in the portion of Ethacrynate Sodium for Injection 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 Ethacrynic Acid RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: Equivalent to 1 mg/mL of ethacrynic acid in Sterile Water for Injection

Acceptance criteria: 5.0–7.0

Sterility Tests 〈71〉: Meets the requirements

Bacterial Endotoxins Test 〈85〉: NMT 5.0 USP Endotoxin Units/mg of ethacrynate sodium

Constituted Solution: At the time of use, it meets the requirements in Injections and Implanted Drug Products 〈1〉, Specific Tests, Completeness and clarity of solutions.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution .

Labeling: Label it to indicate that it was prepared by freeze-drying, having been filled into its container in the form of a true solution.

USP Reference Standards 〈11〉

USP Ethacrynic Acid RS