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A mass spectrometric method for the determination of stable isotope labeled phenytoin suitable for pulse dosing studies
Author(s) -
van Langenhove A.,
Costello C. E.,
Biller J. E.,
Biemann K.,
Browne T. R.
Publication year - 1980
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200071126
Subject(s) - dosing , phenytoin , chemistry , isotope , stable isotope ratio , pulse (music) , chromatography , radiochemistry , medicine , computer science , epilepsy , organic chemistry , physics , quantum mechanics , telecommunications , psychiatry , detector
Abstract A gas chromatographic mass spectrometric method has been developed for the determination in biological fluids of phenytoin (5,5‐diphenylhydantoin), 5‐(4‐hydroxyphenyl)‐5‐phenylhydantoin (the major metabolite of phenytoin), and simultaneously, their stable isotope labeled analog [5,5‐diphenyl‐2‐ 13 C‐1,3‐ 15 N 2 ‐hydantoin and 5‐( ‐hydroxyphenyl)‐5‐phenyl‐2‐ 13 C‐1,3‐ 15 N 2 ‐hydantoin].Quantification was achieved by an isotopic dilution technique: 5,5‐di(pentadeuterophenyl)‐hydantoin and 5‐(4‐hydroxy‐3,5‐dideuterophenyl)‐5‐phenyl‐2‐ 13 C‐1,3‐ 15 N 2 ‐hydantoin were used as internal standards. Molecular ion abundances of the permethylated derivatives were measured using a limited mass range repetitive scanning technique. The method is accurate, selective, reproducible and linear for analysis of 1.0 ml of serum and 0.5 ml of urine samples at the expected concentrations of drug (serum: 0.1‐30.0 μg ml −1 ) and metabolite (serum: 0.1‐10.0 μg ml −1 ; urine: 5.0‐200.0 μg ml −1 ). The pharmacological equivalence of labeled and unlabeled phenytoin is demonstrated for a human volunteer. The results are discussed in the light of the further applications of the method, i.e. determination of the pharmacokinetics of a pulse dose of the labeled drug administered to patients who are taking a steady state dose of the unlabeled drug.