Determination of plasma topiramate concentration using LC-MS/MS for pharmacokinetic and bioequivalence studies in healthy Korean volunteers.
A rapid, simple and validated liquid chromatography coupled to tandem mass spectrometric method (LC-MS/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 C18 column using acetonitrile-0.1% 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(-) and selectivity was achieved by MS/MS analysis, m/z 338.0 --> 77.5 and m/z 357.1 --> 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 20-5000 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 inter-day and intra-day accuracy were in the ranges of 99.24-116.63 and 93.45-108.68%, respectively, and inter-day and intra-day 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.
Park
Jin-Hee
JH
Department of Pharmacology and Institute of Biomedical Sciences, College of Medicine, Hanyang University, Seoul, South Korea.
Park
Yoo-Sin
YS
Lee
Min-Ho
MH
Rhim
Si-Youn
SY
Song
Jae-Chul
JC
Lee
Soo-Jin
SJ
Kim
Jung-Mogg
JM
Shaw
Leslie M
LM
Kang
Ju-Seop
JS
D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007723:Korea; D012016:Reference Values; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose