Study on the Pharmacokinetics and BioequivaIence of Mifepristone in Healthy Volunteers

Objective To establish an LC-MS/MS method for the determination of mifepristone in human plasma and to evaluate the pharmacokinetics and bioequivalence of mifepristone hydrochloride tablets in healthy volunteers.Methods A 50 mg dose of the reference or test tablet was given to 24 healthy female volunteers in a randomized two-way crossover design.The plasma concentration of the drug was assayed by LC-MS/MS.Chromatographic separation was carried out on a Spursil C18 column(4.6 mm×150 mm,5 μm) at 35 ℃,with a mobile phase consisting of methanol-20 mmol · L-1 ammonium acetate containing 0.2% formic acid(12∶ 88).Detection and quantification were performed by mass spectrometry in the multiple reaction monitoring mode with positive electrospray ionization m/z at 430.3→372.2 for mifepristone and 285.1→193.1 for diazepam(internal standard),respectively.The main pharmacokinetic parameters and bioequivalence of the two formulations were evaluated.Results The LOQ of the method for mifepristone in plasma was 10 ng · ml-1 and the calibration curve was linear over the range of 10-3000 ng · ml-1.The intra-and inter-run standard deviation was less than 15%.The major pharmacokinetic parameters were as follows:tmax(0.88±0.27) and(0.81±0.42)h,Cmax(1332±373.3) and(1479±388.3) μg · L-1,t1/2(25.7±8.0) and(25.9±10.0) h,AUC(0-120 h)(16 410±4086) and(16 673±4458) μg · h · L-1,respectively.The relative bioavailability of the test product to the reference was 114.6%.Conclusion This method is successfully applied to pharmacokinetic studies.The two formulations are bioequivalent.