A capillary GC-MS method for analysis of phenytoin and [C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies |
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Authors: | Michael H Nelson Angela K Birnbaum Peter J Nyhus Rory P Remmel |
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Institution: | University of Minnesota, College of Pharmacy, Division of Experimental and Clinical Pharmacology, 8-101 Weaver-Densford Hall, 308 Harvard St. SE, 55455 Minneapolis MN, USA |
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Abstract: | 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. |
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Keywords: | drug blood level phenytoin |
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