Ketoconazole
;)
Piperazine,1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-,cis-.
(±)-cis-1-Acetyl-4-[p-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine [65277-42-1].
»Ketoconazole contains not less than 98.0percent and not more than 102.0percent of C26H28Cl2N4O4,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification,Infrared Absorption á197Kñ.
Specific rotation á781Sñ:
between -1
and +1(t=20).
and +1(t=20).
Test solution:
40mg per mL,in methanol.
Loss on drying á731ñ—
Dry it in vacuum at 80for 4hours:it loses not more than 0.5%of its weight.
for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%from 2g.
Heavy metals,Method IIá231ñ:
0.002%.
Chromatographic purity—
Dissolve 30mg in 3.0mLof chloroform (Test solution).Dissolve a suitable quantity of USP Ketoconazole RSin chloroform to obtain a Standard solutionhaving a known concentration of 10mg per mL.Dilute a portion of this solution quantitatively with chloroform to obtain a Diluted standard solutionhaving a concentration of 1.0mg per mL.Apply separate 10-µLportions of the Test solutionand the Standard solutionand a 2-µLportion of the Diluted standard solutionto the starting line of a suitable 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 a suitable 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,and air-dry.Expose the plate to iodine vapors in a closed chamber,and locate the spots:the principal spot obtained from the Test solutionhas about the same size and RFvalue as that obtained from the Standard solution,and the sum of the intensities of any secondary spots obtained from the Test solutiondoes not exceed the intensity of the principal spot obtained from the Diluted standard solution.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay—
Dissolve about 200mg of Ketoconazole,accurately weighed,in 40mLof glacial acetic acid.Titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 26.57mg of C26H28Cl2N4O4.
Auxiliary Information—
Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1098
Phone Number:1-301-816-8394