Tolmetin Sodium

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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C₁₅H₁₄NNaO₃ · 2H₂O  315.30

C₁₅H₁₄NNaO₃  279.27

1H-Pyrrole-2-acetic acid, 1-methyl-5-(4-methylbenzoyl)-, sodium salt, dihydrate;

Sodium 1-methyl-5-p-toluoylpyrrole-2-acetate dihydrate CAS RN®: 64490-92-2; UNII: 02N1TZF99F.

Anhydrous CAS RN®: 35711-34-3; UNII: WL259637KX.

1 DEFINITION

Tolmetin Sodium contains NLT 98.0% and NMT 102.0% of tolmetin sodium (C₁₅H₁₄NNaO₃), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Change to read:

2.2 B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 10 µg/mL in pH 7 phosphate buffer (see Reagents, Indicators, and Solutions-Buffer Solutions)

Medium: pH 7 phosphate buffer (see Reagents, Indicators, and Solutions-Buffer Solutions)

Acceptance criteria: Meets the requirements

2.3 C. Identification Tests-General, Sodium 〈191〉

Sample solution: 50 mg/mL

Acceptance criteria: Meets the requirements of the test for sodium

3 ASSAY

3.1 Procedure

Sample: 300 mg

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Endpoint detection: Potentiometric

Analysis: Dissolve the Sample by warming in 150 mL of glacial acetic acid. Cool to room temperature, and titrate with Titrant. Perform a blank determination, and make any necessary correction. Each mL of Titrant is equivalent to 27.93 mg of tolmetin sodium (C₁₅H₁₄NNaO₃).

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

4 IMPURITIES

4.1 Organic Impurities

Standard stock solution: 12.5 mg/mL of USP Tolmetin Sodium RS in methanol

Standard solution: 62.5 µg/mL of USP Tolmetin Sodium RS in methanol from Standard stock solution

Sample solution: 12.5 mg/mL of Tolmetin Sodium in methanol

Chromatographic system

• (See Chromatography 〈621〉, Thin-Layer Chromatography.)
• Mode: TLC
• Absorbent: 0.25-mm layer of chromatographic silica gel mixture
• Application volume: 20 µL
• Developing solvent system: Chloroform and glacial acetic acid (95:5)

Analysis

Samples: Standard stock solution, Standard solution, and Sample solution

Develop the chromatogram in the solvent system until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, air-dry, and view under short-wavelength UV light.

Acceptance criteria: The Rf value of the principal spot of the Sample solution corresponds to that of the Standard stock solution. Any other spot of the Sample solution does not exceed in size or intensity of the principal spot of the Standard solution (0.5%), and the sum of the total impurities, based on a comparison of the intensities of all such other spots with the Standard solution, does not exceed 2.0%.

5 SPECIFIC TESTS

5.1 Loss on Drying 〈731〉

Analysis: Dry a sample under vacuum at 60° for 4 h.

Acceptance criteria: 10.4%–12.4%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Tolmetin Sodium RS