Tolmetin Sodium Capsules
» Tolmetin Sodium Capsules contain an amount of tolmetin sodium equivalent to not less than 93.0 percent and not more than 107.0 percent of the labeled amount of tolmetin (C15H15NO3).
Packaging and storage— Preserve in tight containers.
Identification—
A: Transfer a quantity of Capsule contents, equivalent to about 10 mg of tolmetin, to a 100-mL volumetric flask. Add about 50 mL of methanol, shake for 2 minutes, dilute with methanol to volume, and mix. Filter a portion of this solution, transfer 10 mL of the filtrate to a second 100-mL volumetric flask, dilute with 0.1 N sodium hydroxide to volume, and mix: the UV absorption spectrum of the solution so obtained exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Tolmetin Sodium RS, concomitantly measured.
B: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a major peak for tolmetin, the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation obtained as directed in the Assay.
Dissolution—
Medium— Dissolve 2.0 g of sodium chloride in 7.0 mL of hydrochloric acid, and add water to make 1000 mL (Solution A). Dissolve 6.8 g of monobasic potassium phosphate in 250 mL of water, mix, and add 190 mL of 0.2 N sodium hydroxide and 400 mL of water. Adjust the solution with 0.2 N sodium hydroxide to a pH of 7.4 to 7.6. Dilute with water to 1000 mL (Solution B). Add 336 mL of Solution A to 664 mL of Solution B, mix, and adjust the solution with small amounts of either solution to a pH of 4.5; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure— Determine the amount of C15H15NO3 dissolved from UV absorbances at the wavelength of maximum absorbance at about 322 nm of filtered portions of the solution under test, suitably diluted with 0.1 N sodium hydroxide, in comparison with a Standard solution having a known concentration of USP Tolmetin Sodium RS in the same medium.
Tolerances— Not less than 85% (Q) of the labeled amount of C15H15NO3 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Assay—
pH 2.7 buffer solution— Dissolve 1.7 g of tetrabutylammonium phosphate in 1000 mL of water, and adjust by the addition of phosphoric acid to a pH of 2.7 ± 0.1.
Mobile phase— Prepare a filtered and degassed mixture of 64 parts of pH 2.7 buffer solution and 36 parts of acetonitrile, making adjustments if necessary (see System Suitability under Chromatography 621).
Solvent mixture— Mix 400 mL of acetonitrile with 600 mL of 0.01 N sodium hydroxide.
Standard preparation— Dissolve an accurately weighed quantity of USP Tolmetin Sodium RS in Solvent mixture to obtain a solution having a known concentration of about 0.65 mg of anhydrous tolmetin sodium per mL.
Assay preparation— Remove, as completely as possible, the contents of not less than 20 Capsules, weigh, and mix. Transfer an accurately weighed portion of the powder, equivalent to about 60 mg of tolmetin, to a 100-mL volumetric flask. Add about 75 mL of Solvent mixture, and shake by mechanical means for 30 minutes. Dilute with Solvent mixture to volume, mix, and filter through a filter having a porosity of 0.45 µm or less.
Resolution solution— Dissolve suitable quantities of p-toluic acid and USP Tolmetin Sodium RS in Solvent mixture to obtain a solution containing 200 µg and 500 µg, respectively, in each mL.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7, and is operated at a temperature of 40 ± 1.0. The flow rate is about 3 mL per minute. Chromatograph the Standard preparation and the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between the p-toluic acid and tolmetin sodium peaks is not less than 1.2, and the relative standard deviation for replicate injections of the Standard preparation is not more than 3.0%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C15H15NO3 in the portion of Capsule contents taken by the formula:
100C(257.29 / 279.27)(rU / rS)
in which C is the concentration, in mg per mL, of USP Tolmetin Sodium RS in the Standard preparation, 257.29 and 279.27 are the molecular weights of tolmetin and anhydrous tolmetin sodium, respectively, and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Clydewyn M. Anthony, Ph.D.
Scientist
1-301-816-8139
(MDCCA05) Monograph Development-Cough Cold and Analgesics
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
USP32–NF27 Page 3770
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.