Indomethacin 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

Indomethacin for Injection contains an amount of Indomethacin Sodium equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of indomethacin (C₁₉H₁₆CINO₄).

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.

B. The UV absorption spectrum of the indomethacin peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Methanol, phosphoric acid, and water (600:1:400)

Diluent: Acetonitrile, phosphoric acid, and water (300:1:700)

Standard solution: 0.1 mg/mL of USP Indomethacin RS prepared as follows. Dissolve a suitable amount of USP Indomethacin RS with 30% of the final volume of acetonitrile, and dilute with water to volume.

Sample stock solution: Nominally 0.5 mg/mL of indomethacin in Diluent from NLT 10 containers of Indomethacin for Injection

Sample solution: Nominally 0.1 mg/mL of indomethacin in Diluent from the Sample stock solution. Pass through a filter of 0.5-µm or finer pore size. Use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

Column: 3.9-mm x 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution Calculate the percentage of the labeled amount of indomethacin (C₁₉H₁₆CINO₄) in the portion of Indomethacin for Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of indomethacin from the Sample solution

r_S = peak area of indomethacin from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905): Meets the requirements

5 IMPURITIES

5.1 CONTENT OF INDOMETHACIN RELATED COMPOUND B

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

Standard stock solution: 0.22 mg/mL of USP Indomethacin Related Compound B RS in acetonitrile

Standard solution: 0.00044 mg/mL of USP Indomethacin Related Compound B RS prepared as follows. Transfer an adequate volume of the Standard stock solution to a suitable volumetric flask, and add 30% of the final volume of acetonitrile. Dilute with water to the final volume.

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of indomethacin related compound B in the portion of Indomethacin for Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of indomethacin related compound B from the Sample solution

r_S = peak area of indomethacin related compound B from the Standard solution s

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

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

Acceptance criteria: NMT 2.2%

6 SPECIFIC TESTS

CONSTITUTED SOLUTION: At the time of use, it meets the requirements for Injections and Implanted Drug Products (1), Specific Tests, Completeness and clarity of solutions.

STERILITY TESTS (71): Meets the requirements

BACTERIAL ENDOTOXINS TEST (85)

Sample solution: Nominally 1.0 mg/mL of indomethacin in LAL Reagent Water from Indomethacin for Injection

Acceptance criteria: NMT 20.0 USP Endotoxin Units/mg of indomethacin

PARTICULATE MATTER IN INJECTIONS (788): Meets the requirements for small-volume injections

PH (791)

Sample solution: A solution in water (1 in 2000) containing 0.3 mL of saturated potassium chloride solution per 100 mL

Acceptance criteria: 5.0-7.0

OTHER REQUIREMENTS: It meets the requirements in Labeling (7), Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Store at controlled room temperature. Protect from light. Preserve as described in Packaging and Storage Requirements

(659), Injection Packaging, Packaging for constitution.

USP REFERENCE STANDARDS (11)

USP Indomethacin RS

USP Indomethacin Related Compound B RS

4-Chlorobenzoic acid.

C₇H₅CIO₂  156.57