A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies1

Michael H. Nelson, Angela K Birnbaum, Peter J. Nyhus, Rory P Remmel

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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. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)1311-1323
Number of pages13
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume17
Issue number8
DOIs
StatePublished - Sep 30 1998

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Pharmacokinetics
Phenytoin
Plasmas
Assays
Isotopes
Hydantoins
Epilepsy
Prodrugs
Liquids
Rats

Keywords

  • Gas chromatography-mass spectrometry
  • Pharmacokinetics
  • Phenytoin
  • Pulse dosing
  • Stable isotope

Cite this

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title = "A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies1",
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. Copyright (C) 1998 Elsevier Science B.V.",
keywords = "Gas chromatography-mass spectrometry, Pharmacokinetics, Phenytoin, Pulse dosing, Stable isotope",
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T1 - A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies1

AU - Nelson, Michael H.

AU - Birnbaum, Angela K

AU - Nyhus, Peter J.

AU - Remmel, Rory P

PY - 1998/9/30

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N2 - 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.

AB - 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.

KW - Gas chromatography-mass spectrometry

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