Stable isotope analogues of phenytoin are useful for pulse dose pharmacokinetic studies in epilepsy patients. A simultaneous assay was developed to quantitate phenytoin (5,5-diphenylhydantoin) and its stable isotope analogue [13C3]-phenytoin (5,5-diphenyl-2,4,5-13C3-hydantoin) from plasma. Quantitation was achieved by GC-MS analysis of liquid/liquid extracted plasma samples, with [2H10]-phenytoin (5,5-di(pentadeuterophenyl)-hydantoin) as an internal standard. The total coefficients of variance (C.V.(t)) were <7% for phenytoin (2.5-40 μg ml-1) and <10.3% for [13C3]-phenytoin (0.1-6.0 μg ml-1). The accuracy of the assay varied from 87.8-100.1% (phenytoin, 2.5-40 μg ml-1) and 89.6-116.3% ([13C3]-phenytoin, 0.02-6.0 μg ml-1). The assay was tested under in vivo conditions by administration of a pulse dose of the stable isotope analogue to a single rat dosed to steady-state with fosphenytoin, a phenytoin prodrug. The results of the in vivo experiment demonstrate the usefulness of this assay for future pharmacokinetic studies in special population epilepsy patients. Copyright (C) 1998 Elsevier Science B.V.
Copyright 2007 Elsevier B.V., All rights reserved.
- Gas chromatography-mass spectrometry
- Pulse dosing
- Stable isotope