Ketoconazole Tablets
»Ketoconazole Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of C26H28Cl2N4O4.
Packaging and storage— Preserve in well-closed containers.
Identification— Transfer a quantity of finely powdered Tablets,equivalent to about 50mg of ketoconazole,to a suitable flask,add 50mLof chloroform,shake for about 2minutes,and filter.Apply separate 10-µLportions of this solution and of a Standard solution of USP Ketoconazole RSin chloroform containing 1mg per mLto the starting line of a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in an unsaturated chamber with a solvent system consisting of a mixture of n-hexane,ethyl acetate,methanol,water,and glacial acetic acid (42:40:15:2:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,air-dry,and view under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
Methanol–methylene chloride— Mix equal volumes of methanol and methylene chloride.
Mobile phase— Prepare a suitable (7:3)mixture of a solution of diisopropylamine in methanol (1in 500)and ammonium acetate solution (1in 200).
Internal standard solution— Dissolve USP Terconazole RSin Methanol–methylene chlorideto obtain a solution containing about 5mg per mL.
Standard preparation— Transfer about 20mg of USP Ketoconazole RS,accurately weighed,to a 50-mLvolumetric flask,add 5.0mLof Internal standard solution,dilute with Methanol–methylene chlorideto volume,and mix.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 200mg of ketoconazole,to a suitable screw-capped bottle,add 50.0mLof Methanol–methylene chloride,shake by mechanical means for 30minutes,and centrifuge.Transfer 5.0mLof the clear supernatant so obtained to a 50-mLvolumetric flask,add 5.0mLof Internal standard solution,dilute with Methanol–methylene chlorideto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 225-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 3mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%,and the resolution,R,between ketoconazole and terconazole is not less than 2.0.
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.The relative retention times are about 0.6for ketoconazole and 1.0for terconazole.Calculate the quantity,in mg,of C26H28Cl2N4O4in the portion of Tablets taken by the formula:
10WS(RU/RS),
in which WSis the weight,in mg,of USP Ketoconazole RStaken,and RUand RSare the ratios of the peak responses of ketoconazole to those of terconazole from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1099
Pharmacopeial Forum:Volume No.30(4)Page 1256
Phone Number:1-301-816-8394