Tolmetin Sodium Capsules »Tolmetin Sodium Capsules contain an amount of tolmetin sodium equivalent to not less than 93.0percent and not more than 107.0percent of the labeled amount of tolmetin (C15H15NO3). Packaging and storage— Preserve in tight containers. USP Reference standards á11ñ USP Tolmetin Sodium RS. Identification— A: Transfer a quantity of Capsule contents,equivalent to about 10mg of tolmetin,to a 100-mLvolumetric flask.Add about 50mLof methanol,shake for 2minutes,dilute with methanol to volume,and mix.Filter a portion of this solution,transfer 10mLof the filtrate to a second 100-mLvolumetric flask,dilute with 0.1Nsodium hydroxide to volume,and mix:the UVabsorption 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 preparationobtained as directed in the Assayexhibits a major peak for tolmetin,the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparationobtained as directed in the Assay. Dissolution— Medium— Dissolve 2.0g of sodium chloride in 7.0mLof hydrochloric acid,and add water to make 1000mL(Solution A).Dissolve 6.8g of monobasic potassium phosphate in 250mLof water,mix,and add 190mLof 0.2Nsodium hydroxide and 400mLof water.Adjust the solution with 0.2Nsodium hydroxide to a pHof 7.4to 7.6.Dilute with water to 1000mL(Solution B).Add 336mLof Solution Ato 664mLof Solution B,mix,and adjust the solution with small amounts of either solution to a pHof 4.5;900mL. Apparatus 2: 50rpm. Time: 30minutes. Procedure— Determine the amount of C15H15NO3dissolved from UVabsorbances at the wavelength of maximum absorbance at about 322nm of filtered portions of the solution under test,suitably diluted with 0.1Nsodium hydroxide,in comparison with a Standard solution having a known concentration of USP Tolmetin Sodium RSin the same medium. Tolerances— Not less than 85%(Q)of the labeled amount of C15H15NO3is dissolved in 30minutes. Uniformity of dosage units á905ñ: meet the requirements. Assay— pH2.7buffer solution— Dissolve 1.7g of tetrabutylammonium phosphate in 1000mLof water,and adjust by the addition of phosphoric acid to a pHof 2.7±0.1. Mobile phase— Prepare a filtered and degassed mixture of 64parts of pH2.7buffer solutionand 36parts of acetonitrile,making adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Solvent mixture— Mix 400mLof acetonitrile with 600mLof 0.01Nsodium hydroxide. Standard preparation— Dissolve an accurately weighed quantity of USP Tolmetin Sodium RSin Solvent mixtureto obtain a solution having a known concentration of about 0.65mg of anhydrous tolmetin sodium per mL. Assay preparation— Remove,as completely as possible,the contents of not less than 20Capsules,weigh,and mix.Transfer an accurately weighed portion of the powder,equivalent to about 60mg of tolmetin,to a 100-mLvolumetric flask.Add about 75mLof Solvent mixture,and shake by mechanical means for 30minutes.Dilute with Solvent mixtureto volume,mix,and filter through a filter having a porosity of 0.45µm or less. Resolution solution— Dissolve suitable quantities of p-toluic acid and USP Tolmetin Sodium RSin Solvent mixtureto obtain a solution containing 200µg and 500µg,respectively,in each mL. Chromatographic system (see Chromatography á621ñ)—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 3mLper minute.Chromatograph the Standard preparationand 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 preparationis not more than 3.0%. Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C15H15NO3in the portion of Capsule contents taken by the formula: 100C(257.29/279.27)(rU/rS), in which Cis the concentration,in mg per mL,of USP Tolmetin Sodium RSin the Standard preparation,257.29and 279.27are the molecular weights of tolmetin and anhydrous tolmetin sodium,respectively,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist Expert Committee:(PA2)Pharmaceutical Analysis 2 USP28–NF23Page 1949 Phone Number:1-301-816-8143