ACID STAGE —

Medium: 0.1Nhydrochloric acid;900mL.

Apparatus 2 (paddles constructed of,or coated with,polytef being used):50rpm.

Procedure— At the end of 2hours,remove each Tablet,or the major portion thereof if the Tablet is not intact,from the individual vessels,and subject them to the test in the Buffer stage.To the 0.1Nhydrochloric acid remaining in each vessel,add 20.0mLof 5Nsodium hydroxide,and stir for 5minutes.Determine the amount of C14H10Cl2NNaO2dissolved from UVabsorbances at the wavelength of maximum absorbance at about 276nm of filtered portions of the solution under test in comparison with a Standard solution prepared as follows.Transfer about 68mg of USP Diclofenac Sodium RS,accurately weighed,to a 100-mLvolumetric flask,add 10.0mLof 0.1Nsodium hydroxide,dilute with water to volume,and mix.Transfer 2.0mLof this solution to a second 100-mLvolumetric flask,dilute with a mixture of 0.1Nhydrochloric acid and 5Nsodium hydroxide (900:20)to volume,and mix.This Standard solution contains about 13.6µg of USP Diclofenac Sodium RSper mL.

BUFFER STAGE —

pH6.8Phosphate buffer— Dissolve 76g of tribasic sodium phosphate in water to obtain 1000mLof solution.Mix 250mLof this solution with 750mLof 0.1Nhydrochloric acid,and,if necessary,adjust with 2Nhydrochloric acid or 2Nsodium hydroxide to a pHof 6.8±0.05.

Medium: pH6.8Phosphate buffer;900mL.

Apparatus 2: 50rpm.

Procedure— At the end of 45minutes,determine the amount of C14H10Cl2NNaO2dissolved from UVabsorbances at the wavelength of maximum absorbance at about 276nm of filtered portions of the solutions under test,suitably diluted with Dissolution Medium,in comparison with a Standard solution prepared as follows.Transfer about 68mg of USP Diclofenac Sodium RS,accurately weighed,to a 100-mLvolumetric flask,add 10.0mLof 0.1Nsodium hydroxide,dilute with water to volume,and mix.Transfer 3.0mLof this solution to a second 100-mLvolumetric flask,dilute with Dissolution Medium,as obtained in the Buffer stage,to volume,and mix.This Standard solution contains about 0.02mg of USP Diclofenac Sodium RSper mL.

Tolerances— Not less than 75%(Q)of the labeled amount of C14H10Cl2NNaO2is dissolved.

pH2.5Phosphate buffer,Mobile phase,Diluent,Resolution solution,and Chromatographic system— Proceed as directed in the Assay.

Standard solution— Prepare a solution having a known concentration of about 0.8mg per mLof USP Diclofenac Related Compound A RSin methanol.Dilute an accurately measured volume of this stock solution with Diluentto obtain a solution having a known concentration of about 4µg per mL.

Test solution— Use the Assay preparation,prepared as directed in the Assay.

Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses over a period of 40minutes.Calculate the percentage of diclofenac related compound Ain relation to the quantity of diclofenac sodium in the Tablets taken by the formula: in which Cis the concentration,in µg per mL,of USP Diclofenac Related Compound A RSin the Standard solution;Ais the quantity,in mg,of diclofenac sodium (C14H10Cl2NNaO2)in the Tablets taken for the Assay,as determined in the Assay;and rUand rSare the diclofenac related compound Apeak responses obtained from the Test solutionand the Standard solution,respectively:not more than 0.5%is found.Calculate the percentage of each other impurity,other than diethyl phthalate,if present,in relation to the diclofenac sodium in the Tablets taken by the formula: in which riis the peak response for each impurity obtained from the Test solution,and the other terms are as defined above:not more than 1.0%of any individual impurity is found,and the sum of all of the impurities found is not more than 1.5%.

pH2.5Phosphate buffer— Mix equal volumes of 0.01Mphosphoric acid and 0.01Mmonobasic sodium phosphate.If necessary,adjust with additional portions of the appropriate component to a pHof 2.5±0.2.

Mobile phase— Prepare a filtered and degassed mixture of methanol and pH2.5Phosphate buffer(700:300).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).[NOTE—Increasing the proportion of buffer increases resolution.]

Diluent— Prepare a mixture of methanol and water (70:30).

Standard preparation— Prepare a solution of USP Diclofenac Sodium RSin Diluenthaving a known concentration of about 0.75mg per mL.

Resolution solution— Prepare a solution in Diluentcontaining 20µg of diethyl phthalate,7.5µg of USP Diclofenac Related Compound A RS,and 0.75mg of USP Diclofenac Sodium RSper mL.

Assay preparation— Transfer 20Tablets to a volumetric flask of such capacity that when filled to volume,a concentration of about 0.75mg of diclofenac sodium per mLis obtained.Add Diluentto about 70%of the capacity of the flask,and shake by mechanical means for not less than 30minutes to disintegrate the Tablets.Cool to room temperature,dilute with Diluentto volume,and mix.Pass a portion of the solution through a filter of 0.5-µm or finer porosity,and use the filtrate as the Assay preparation.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×25-cm column that contains packing L7(end-capped).The flow rate is about 1mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.5for diethyl phthalate,0.6for diclofenac related compound A,and 1.0for diclofenac;and the resolution,R,between diethyl phthalate and diclofenac related compound Ais not less than 2.2,and between diclofenac related compound Aand diclofenac is not less than 6.5.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the quantity,in mg,of diclofenac sodium (C14H10Cl2NNaO2)in each Tablet taken by the formula: in which Cis the concentration,in mg per mL,of USP Diclofenac Sodium RSin theStandard preparation;Vis the volume of the flask used,in mL;and rUand rSare the diclofenac peak responses obtained from the Assay preparationand the Standard preparation,respectively.