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

✍ Scribed by A. Barrish; T. V. Olah; G. J. Gatto; M. R. Dobrinska; J. D. Gilbert

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 428 KB
• Volume: 10
• Category: Article
• ISSN: 0951-4198
• DOI: 10.1002/(sici)1097-0231(19960715)10:9<1033::aid-rcm616>3.0.co;2-4

✦ Synopsis

MK-0462 (rizatriptan) is a

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-"C,, "N3-] stable-isotopelabelled analogue for which the lower quantifiable limit was 0.1 ng mL-'. The assay has been applied to study the pharmacokinetics of MK-0462 after simultaneous oral and intravenous administration of the drug and its stableisotope-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.