Indomethacin

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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C₁₉H₁₆ClNO₄  357.79

1H-Indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-;

1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid CAS RN^®: 53-86-1; UNII: XXE1CET956.

1 DEFINITION

Indomethacin contains NLT 98.0% and NMT 102.0% of indomethacin (C₁₉H₁₆ClNO₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. ASPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197M (CN 1-May-2020)

B.

The retention time of the indomethacin peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Solution A: 0.1% formic acid

Solution B: Acetonitrile

Mobile phase: Solution A and Solution B (55:45)

Diluent: Solution A and Solution B (55:45), adjusted with 0.2 M sodium hydroxide to a pH of 8.0

System suitability solution: 2.0 mg/mL of USP Indomethacin RS, 0.002 mg/mL of USP Indomethacin Related Compound A RS, and 0.01 mg/mL of USP Indomethacin Related Compound B RS, prepared as follows. Transfer a quantity of USP Indomethacin RS to a suitable volumetric flask. Add 50% of the final volume of acetonitrile and sonicate to dissolve. Add suitable amounts of USP Indomethacin Related Compound A RS and USP Indomethacin Related Compound B RS to the resulting solution, sonicate to dissolve if necessary, and dilute with Diluent to volume.

Standard solution: 0.5 mg/mL of USP Indomethacin RS in Diluent. Sonicate to dissolve.

Sample solution: 0.5 mg/mL of Indomethacin in Diluent. Sonicate to dissolve.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for indomethacin related compound A and indomethacin related compound B are 0.24 and 0.37, respectively.]

Suitability requirements

Resolution: NLT 2.0 between indomethacin related compound B and indomethacin related compound A, System suitability solution

Tailing factor: NMT 2.0 for indomethacin, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of indomethacin (C₁₉H₁₆ClNO₄) in the portion of Indomethacin taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of indomethacin from the Sample solution

r_S = peak response of indomethacin from the Standard solution

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

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

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.2%

4.2 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.002 mg/mL of USP Indomethacin RS, 0.002 mg/mL of USP Indomethacin Related Compound A RS, and 0.01 mg/mL of USP Indomethacin Related Compound B RS in Diluent. Sonicate to dissolve.

Sample solution: 2.0 mg/mL of Indomethacin, prepared as follows. Transfer a quantity of Indomethacin to a suitable volumetric flask. Add 50% of the final volume of acetonitrile and sonicate to dissolve. Dilute with Diluent to volume.

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2.0 between indomethacin related compound A and indomethacin related compound B

Tailing factor: NMT 2.0 for indomethacin related compound A, indomethacin related compound B, and indomethacin

Relative standard deviation: NMT 5.0% for indomethacin related compound A, indomethacin related compound B, and indomethacin

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of indomethacin related compound A and indomethacin related compound B in the portion of Indomethacin taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of indomethacin related compound A or indomethacin related compound B from the Sample solution

r_S = peak response of indomethacin related compound A or indomethacin related compound B from the Standard solution

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

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

Calculate the percentage of any individual unspecified impurity in the portion of Indomethacin taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any individual unspecified impurity from the Sample solution

r_S = peak response of indomethacin from the Standard solution\

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

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

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry at a pressure below 5 mm of mercury at 100° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers.

USP REFERENCE STANDARDS (11)

USP Indomethacin RS

USP Indomethacin Related Compound A RS

(5-Methoxy-2-methylindol-3-yl)acetic acid.

C₁₂H₁₃NO₃  219.24

USP Indomethacin Related Compound B RS

4-Chlorobenzoic acid.

C₇H₅ClO₂  156.57