title: A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies.
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 micrograms ml-1) and < 10.3% for [13C3]-phenytoin (0.1-6.0 micrograms ml-1). The accuracy of the assay varied from 87.8-100.1% (phenytoin, 2.5-40 micrograms ml-1) and 89.6-116.3% ([13C3]-phenytoin, 0.02-6.0 micrograms 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.
authors.affiliation: University of Minnesota, College of Pharmacy, Division of Experimental and Clinical Pharmacology, Minneapolis 55455, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Nelson
authors.forename: A K
authors.initials: AK
authors.lastname: Birnbaum
authors.forename: P J
authors.initials: PJ
authors.lastname: Nyhus
authors.forename: R P
authors.initials: RP
authors.lastname: Remmel
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D007554:Isotopes; D008297:Male; D015394:Molecular Structure; D010672:Phenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards
chemical_list: D000927:Anticonvulsants; D007554:Isotopes; D011355:Prodrugs; D010672:Phenytoin; C043114:fosphenytoin