A: Mix a portion of Oral Suspension,equivalent to about 25mg of indomethacin,with 25mLof a 1in 200solution of glacial acetic acid in 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 glacial acetic acid (19:1)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 corresponds to that obtained from the Standard solution.

B: The retention time of the indomethacin peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.

Medium: 0.01MpH7.2phosphate buffer prepared by dissolving 1.36g of monobasic potassium phosphate in 1Lof water and adjusting with 0.1Nsodium hydroxide to a pHof 7.2±0.1;900mL.

Apparatus 2: 50rpm.

Time: 20minutes.

Procedure— Transfer to the surface of theMediumin the dissolution vessel an accurately measured volume of Oral Suspension,freshly mixed and free from air bubbles,equivalent to about 25mg of indomethacin.Determine the amount of C19H16ClNO4dissolved from UVabsorbances at the wavelength of maximum absorbance at about 320nm on filtered portions of the solution under test,suitably diluted with Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Indomethacin RSin the same Medium.[NOTE—An amount of methanol not to exceed 1.0%of the volume of the Standard solution may be used to bring the USP Reference Standard into solution prior to dilution with Medium,and the solution may be sonicated to effect complete dissolution of the USP Reference Standard.]

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

Add the following:

FOR ORAL SUSPENSION PACKAGED IN SINGLE-UNIT CONTAINERS: meets the requirements.USP28

Add the following:

FOR ORAL SUSPENSION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.USP28

5(C4/CA)(rA/r4),

50(C/V)(rU/rS),

Phosphoric acid solution— Dilute 2mLof phosphoric acid with water to make 1000mLof solution.

Solvent mixture— Prepare a solution consisting of a mixture of dehydrated alcohol and butyl alcohol (8:5).

Mobile phase— Prepare a suitable mixture of Phosphoric acid solutionand Solvent mixture(610:390),pass through a suitable filter having a 0.5-µm or finer porosity,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard indomethacin preparation— Transfer about 40mg of USP Indomethacin RS,accurately weighed,to a 50-mLvolumetric flask.Where the Oral Suspension is represented as containing a stated amount of sorbic acid,add 40Jmg of sorbic acid,accurately weighed,Jbeing the ratio of the labeled amount,in mg,of sorbic acid to the labeled amount,in mg,of indomethacin per mLof the Oral Suspension.Add 10mLof Phosphoric acid solutionand 15mLof Solvent mixture,and sonicate for 5minutes.Dilute with Phosphoric acid solutionto volume,and mix.This solution contains about 0.8mg of USP Indomethacin RSand,where added,about 0.8Jmg of sorbic acid.

Standard 4-chlorobenzoic acid preparation— [NOTE—Prepare this Standard 4-chlorobenzoic acid preparation and chromatograph it as directed under Chromatographic systemand Procedure only if the test for Limit of 4-Chlorobenzoic acidis being performed.]Dissolve a suitable quantity of 4-chlorobenzoic acid,accurately weighed,in Solvent mixtureto obtain a solution having a known concentration of about 0.09mg per mL.Transfer 1.0mLof this solution to a 50-mLvolumetric flask containing 15mLof Solvent mixture,dilute with Phosphoric acid solutionto volume,and mix.This solution contains about 1.8µg of 4-chlorobenzoic acid per mL.

Assay preparation— Transfer an accurately measured volume of Oral Suspension,freshly mixed and free from air bubbles,equivalent to about 40mg of indomethacin,to a 50-mLvolumetric flask,add 15mLof Solvent mixture,and sonicate for 10minutes.Dilute with Phosphoric acid solution to volume,mix,and pass through a suitable filter having a 0.5-µm or finer porosity.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 240-nm detector and an 8-mm ×10-cm column that contains packing L1.The flow rate is about 3mLper minute.Chromatograph the Standard indomethacin preparation,and record the peak responses as directed for Procedure:the capacity factor,k¢,for indomethacin is not less than 2.5;the column efficiency determined from the analyte peak is not less than 500theoretical plates;the resolution,R,between sorbic acid (where present)and indomethacin is not less than 4.0;the tailing factor for the analyte peak(s)is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.Chromatograph the Standard 4-chlorobenzoic acid preparation,and record the peak responses as directed for Procedure:the capacity factor,k¢,for the 4-chlorobenzoic acid peak,is not less than 1.0;and the relative standard deviation for replicate injections is not more than 2.5%.

Procedure— Separately inject equal volumes (about 15µL)of the Standard indomethacin preparation,the Standard 4-chlorobenzoic acid preparation,and the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of indomethacin (C19H16ClNO4)in each mLof the Oral Suspension taken by the formula: in which Cis the concentration,in mg per mL,of USP Indomethacin RSin the Standard indomethacin preparation;Vis the volume,in mL,of Oral Suspension taken;and rUand rSare the peak responses of the analyte obtained from the Assay preparationand the Standard indomethacin preparation,respectively.