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The Use of Stable Isotope Labeling and Liquid Chromatography/Tandem Mass Spectrometry Techniques to Study the Pharmacokinetics and Bioavailability of the Antimigraine Drug, MK‐0462 (Rizatriptan) in Dogs
Author(s) -
Barrish A.,
Olah T. V.,
Gatto G. J.,
Dobrinska M. R.,
Gilbert J. D.
Publication year - 1996
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/(sici)1097-0231(19960715)10:9<1033::aid-rcm616>3.0.co;2-4
Subject(s) - chemistry , bioavailability , chromatography , pharmacokinetics , mass spectrometry , drug , tandem mass spectrometry , liquid chromatography–mass spectrometry , pharmacology , medicine
MK‐0462 (rizatriptan) is a 5HT 1D agonist being developed for the treatment of migraine. The assay for this substance in plasma and urine is based on HPLC with tandem mass spectrometry (MS/MS) detection. The procedure has been modified to include the simultaneous determination of the [triazole‐ 13 C 2 , 15 N 3 ‐] stable‐isotope‐labelled analogue for which the lower quantifiable limit was 0.1 ng mL −1 . The assay has been applied to study the pharmacokinetics of MK‐0462 after simultaneous oral and intravenous administration of the drug and its stable‐isotope‐labelled analogue to dogs. The experiment afforded an estimate of plasma clearance concomitant with a precise measurement of the drug's oral bioavailability. The increasing use of LC‐MS/MS in quantitative experiments may renew interest in stable isotopes as tools for pharmaceutical research.