A: Shake a portion of the contents of Capsules,equivalent to about 50mg of indomethacin,with 10mLof acetone for about 2minutes,and filter.Transfer 5mLof the filtrate to a stoppered flask,add 20mLof water,and shake for about 2minutes until a precipitate forms and crystallizes.Filter,and collect the crystals.Dry the crystals in air,then dry at a pressure below 5mm of mercury at 100for 2hours:the IRabsorption spectrum of a potassium bromide dispersion of the dried residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Indomethacin RSthat has been similarly recrystallized from a solution of 25mg in 5mLof acetone.

B: Shake a portion of the contents of Capsules,equivalent to about 25mg of indomethacin,with 25mLof methanol,and filter.Separately apply 2µLof the filtrate so obtained (test solution)and 2µLof a Standard solution in methanol containing 1mg of USP Indomethacin RSper mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture,and dry the spots with the aid of a current of air.Develop the chromatogram in a solvent system consisting of a mixture of chloroform and methanol (4:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,allow it to dry,and locate the spots under short-wavelength UVlight:the intensity and RFvalue of the principal spot obtained from the test solution correspond to that obtained from the Standard solution.

Medium: 1volume of pH7.2phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions)mixed with 4volumes of water;750mL.

Apparatus 1: 100rpm.

Time: 20minutes.

Procedure— Determine the amount of C19H16ClNO4dissolved from UVabsorbances at the wavelength of maximum absorbance at about 318nm of filtered portions of the solution under test,suitably diluted with Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Indomethacin RSin the same medium.

Tolerances— Not less than 80%(Q)of the labeled amount of C19H16ClNO4is dissolved in 20minutes.

Procedure for content uniformity— Transfer the contents of 1Capsule to a 100-mLvolumetric flask,add 10mLof water,and allow to stand for 10minutes,swirling occasionally.Add 60mLof methanol,shake for 10minutes,dilute with methanol to volume,mix,and centrifuge.Dilute a portion of the clear solution quantitatively and stepwise,if necessary,with a mixture of equal volumes of methanol and pH7.0phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions)to obtain a solution containing about 25µg of indomethacin per mL.Concomitantly determine the absorbances of this solution and a Standard solution of USP Indomethacin RS,in the methanol and pH7.0phosphate buffer mixture (1:1)having a known concentration of about 25µg per mL,in 1-cm cells at the wavelength of maximum absorbance at about 318nm,with a suitable spectrophotometer,using the methanol and pH7.0phosphate buffer mixture as the blank.Calculate the quantity,in mg,of C19H16ClNO4in the Capsule taken by the formula: in which Tis the labeled quantity,in mg,of indomethacin in the Capsule,Cis the concentration,in µg per mL,of USP Indomethacin RSin the Standard solution,Dis the concentration,in µg per mL,of indomethacin in the test solution,based upon the labeled quantity per Capsule and the extent of dilution,and AUand ASare the absorbances of the solution from the Capsule and the Standard solution,respectively.

Standard preparation— Transfer about 25mg of USP Indomethacin RS,accurately weighed,to a 200-mLvolumetric flask,dissolve in 2mLof methanol,dilute with pH7.2phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions)to volume,and mix.Transfer 25.0mLof this solution to a separator,and extract with three 25-mLportions of methylene chloride.Filter the extracts through a pledget of cotton into a 100-mLvolumetric flask,rinse the filter with methylene chloride,dilute with methylene chloride to volume,and mix to obtain a Standard preparationhaving a known concentration of about 31µg per mL.

Assay preparation— Transfer,as completely as possible,the contents of not less than 20Capsules to a suitable tared container,and determine the average content weight per Capsule.Mix the combined contents,and transfer an accurately weighed portion,equivalent to about 25mg of indomethacin,to a 200-mLvolumetric flask,add 2mLof methanol,shake for 10minutes,dilute with pH7.2phosphate buffer to volume,and mix.Transfer about 50mLto a centrifuge tube,and centrifuge for 15minutes.Transfer 25.0mLof the supernatant to a 125-mLseparator,and extract with three 25-mLportions of methylene chloride.Filter the extracts through a pledget of cotton into a 100-mLvolumetric flask,rinse the filter with methylene chloride,dilute with methylene chloride to volume,and mix.

Procedure— Concomitantly determine the absorbances of the solutions in 1-cm cells at the wavelength of maximum absorbance at about 318nm,with a suitable spectrophotometer,using methylene chloride as the blank.Calculate the quantity,in mg,of C19H16ClNO4in the portion of Capsules taken by the formula: in which Cis the concentration,in µg per mL,of USP Indomethacin RSin the Standard preparation,and AUand ASare the absorbances of the Assay preparationand the Standard preparation,respectively.