Tolmetin Sodium Capsules

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

Tolmetin Sodium Capsules contain an amount of tolmetin sodium equivalent to NLT 93.0% and NMT 107.0% of the labeled amount of tolmetin (C₁₅H₁₅NO₃).

2 IDENTIFICATION

2.1 A. Ultraviolet Absorption

Standard stock solution: 0.1 mg/mL of USP Tolmetin Sodium RS in methanol

Standard solution: 0.01 mg/mL of USP Tolmetin Sodium RS from the Standard stock solution diluted with 0.1 N sodium hydroxide

Sample solution: Transfer a quantity of Capsule contents, equivalent to 10 mg of tolmetin, to a 100-mL volumetric flask. Add 50 mL of methanol, shake for 2 min, and dilute with methanol to volume. Filter a portion of this solution, transfer 10.0 mL of the filtrate to a second 100-mL volumetric flask, and dilute with 0.1 N sodium hydroxide to volume.

Analysis

Samples: Standard solution and Sample solution

Concomitantly measure the UV absorption.

Acceptance criteria: The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as that of the Standard solution.

2.2 B.

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

3 ASSAY

3.1 Procedure

Buffer: 1.7 g/L of tetrabutylammonium phosphate. Adjust with phosphoric acid to a pH of 2.7 ± 0.1.

Mobile phase: Acetonitrile and Buffer (36:64)

Diluent: Acetonitrile and 0.01 N sodium hydroxide (40:60)

System suitability solution: 200 µg/mL of p-toluic acid and 500 µg/mL of USP Tolmetin Sodium RS in Diluent

Standard solution: 0.65 mg/mL of anhydrous tolmetin sodium from USP Tolmetin Sodium RS in Diluent

Sample solution: Transfer the equivalent of 60 mg of tolmetin from the powdered contents of NLT 20 Capsules to a 100-mL volumetric flask. Add 75 mL of Diluent, and shake by mechanical means for 30 min. Dilute with Diluent to volume, and pass through a filter of 0.45-µm or finer pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 15-cm; 5-µm packing L7
• Column temperature: 40 ± 1.0°
• Flow rate: 3 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 1.2 between the p-toluic acid and tolmetin sodium peaks, System suitability solution
• Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tolmetin (C₁₅H₁₅NO₃) in the portion of Capsule contents taken:

Result =(rᵤ/rₛ) × (Cₛ/Cᵤ) × (M_r₁/M_r₂) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of the USP Tolmetin Sodium RS in the Standard solution (mg/mL)

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

M_r₁ = molecular weight of tolmetin, 257.29

M_r₂ = molecular weight of anhydrous tolmetin sodium, 279.27

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Solution A: Dissolve 2.0 g of sodium chloride in 7.0 mL of hydrochloric acid, and add water to 1000 mL.

Solution B: Dissolve 6.8 g of monobasic potassium phosphate in 250 mL of water, and add 190 mL of 0.2 N sodium hydroxide and 400 mL of water. Adjust with 0.2 N sodium hydroxide to a pH of 7.4–7.6. Dilute with water to 1000 mL.

Medium: Solution A and Solution B (336:664). Adjust the solution with small amounts of either solution to a pH of 4.5; 900 mL.

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: USP Tolmetin Sodium RS in Medium at a known concentration

Sample solutions: Sample per Dissolution 〈711〉. Dilute with 0.1 hookup sodium hydroxide, as needed, and filter.

Instrumental conditions

• (See Ultraviolet-Visible Spectroscopy 〈857〉.)
• Mode: UV
• Analytical wavelength: 322 nm

Analysis

Samples: Standard solution and Sample solution

Determine the quantity of tolmetin (C₁₅H₁₅NO₃) dissolved using filtered portions of the solution under test, suitably diluted with 0.1 N sodium hydroxide, in comparison with the Standard solution.

Tolerances: NLT 85% (Q) of the labeled amount of tolmetin (C₁₅H₁₅NO₃) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Tolmetin Sodium RS