Ursodiol Capsules »Ursodiol Capsules contain not less than 90.0percent and not more than 110.0percent of the labeled amount of ursodiol (C24H40O4). Packaging and storage— Preserve in well-closed containers. USP Reference standards á11ñ USP Ursodiol RS. Identification— The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,both relative to the internal standard,as obtained in the Assay. Dissolution á711ñ Medium: 0.2MpH8.4phosphate buffer,prepared by mixing 250mLof 0.2Mmonobasic potassium phosphate,280mLof 0.2Mpotassium hydroxide,and 5mLof 2%sodium lauryl sulfate solution.Adjust with 0.2Mpotassium hydroxide to a pHof 8.4,and dilute with water to 1000mL;1000mL. Apparatus 2: 75rpm. Time: 30minutes. Determine the amount of ursodiol dissolved by employing the following method. Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and 0.075Mmonobasic potassium phosphate (50:50).Adjust with 85%phosphoric acid to a pHof 3.0.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard solution— Dissolve an accurately weighed quantity of USP Ursodiol RS,and dilute quantitatively,and stepwise if necessary,with Mediumto obtain a solution having a known concentration equivalent to that expected in the solution under test. Test solution— Use a filtered portion of the solution under test. Chromatographic system— The liquid chromatograph is equipped with a refractive index detector,a guard column that contains packing L1,and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1mLper minute,and the column and detector temperatures are maintained at 40.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the tailing factor of the ursodiol peak is not more than 1.7;and the relative standard deviation for replicate injections is not more than 2%. Procedure— Separately inject equal volumes (about 50µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentage of C24H40O4dissolved by the formula: 100,000(rU/rS)(C/W), in which rUand rSare the peak responses obtained from the Test solutionand the Standard solution,respectively;Cis the concentration,in mg per mL,of USP Ursodiol RSin the Standard solution;and Wis the labeled amount,in mg,of ursodiol in each capsule. Tolerances— Not less than 80%(Q)of the labeled amount of C24H40O4is dissolved in 30minutes. Uniformity of dosage units á905ñ: meet the requirements for Weight Variation. Assay— Mobile phase,Internal standard solution,Standard preparation,and Chromatographic system— Proceed as directed in the Assayunder Ursodiol. Assay preparation— Accurately weigh the contents of not fewer than 20Capsules,and mix.Transfer an accurately weighed portion of the powder,equivalent to about 200mg of ursodiol,to a 50-mLvolumetric flask.Add about 40mLof methanol,and sonicate for about 15minutes.Cool the mixture to room temperature,dilute with methanol to volume,and centrifuge a portion of this mixture.Transfer 5.0mLof the clear supernatant to a 25-mLvolumetric flask,and dilute with Mobile phaseto volume.Transfer equal amounts of this solution and the Internal standard solutionto a suitable container,mix,and filter. Procedure— Separately inject equal volumes (about 50µL)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 ursodiol (C24H40O4)in the portion of Capsules taken by the formula: 200(CS/CU)(RU/RS), in which CSand CUare the concentrations,in mg per mL,of ursodiol in the Standard preparationand the Assay preparation,respectively;and RUand RSare the ratios of the ursodiol peak to the internal standard peak obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist Expert Committee:(PA4)Pharmaceutical Analysis 4 USP28–NF23Page 2006 Pharmacopeial Forum:Volume No.29(5)Page 1589 Phone Number:1-301-816-8251