Abstract
A rapid, simple and validated liquid chromatography coupled to tandem mass spectrometric method (LCβMS/MS) for topiramate analysis in human plasma has been applied to pharmacokinetic and bioequivalence studies in 24 healthy male Korean volunteers. The procedure involves a simple liquid extraction of topiramate and prednisone (internal standard) with acetonitrile and separation by HPLC equipped with a Capcell Pak C~18~ column using acetonitrileβ0.1% triethylamine (80:20, v/v) as a mobile phase. Detection was carried out on an API 2000 MS system by multiple reactions monitoring mode. The ionization was optimized using ESI(β) and selectivity was achieved by MS/MS analysis, m/z 338.0 β 77.5 and m/z 357.1 β 327.2 for topiramate and prednisone, respectively. The method had a total run time of 2.5 min and showed good linearity over a working range of 20β5000 ng/mL in human plasma with a lower limit of quantification of 20 ng/mL. No metabolic compounds were found to interfere with the analysis. The interβday and intraβday accuracy were in the ranges of 99.24β116.63 and 93.45β108.68%, respectively, and interβday and intraβday precisions were below 6.24 and 5.25%, respectively. This method was successfully applied for pharmacokinetic and bioequivalence studies by analysis of blood samples taken up to 96 h after an oral administration of 100 mg of topiramate in 24 healthy Korean volunteers. Copyright Β© 2008 John Wiley & Sons, Ltd.