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.
MK-0462 (rizatriptan) is a 5HT1D 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-13C2, 15N3-] 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.
Barrish
A
A
Department of Drug Metabolism Merck Research Laboratories West Point, PA 19486, USA.
Olah
T V
TV
Gatto
G J
GJ
Michel
K B
KB
Dobrinska
M R
MR
Gilbert
J D
JD
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004285:Dogs; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics*; D014230:Triazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D014363:Tryptamines
D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan