Barrish A, Olah T V, Gatto G J, Michel K B, Dobrinska M R, Gilbert J D
Department of Drug Metabolism Merck Research Laboratories West Point, PA 19486, USA.
Rapid Commun Mass Spectrom. 1996;10(9):1033-7. doi: 10.1002/(SICI)1097-0231(19960715)10:9<1033::AID-RCM616>3.0.CO;2-4.
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.
MK-0462（利扎曲普坦）是一种正在研发用于治疗偏头痛的5HT1D激动剂。血浆和尿液中该物质的检测基于高效液相色谱-串联质谱（MS/MS）检测。该程序已进行修改，以同时测定[三唑-13C2, 15N3-]稳定同位素标记类似物，其最低可定量限为0.1 ng/mL。该检测方法已应用于研究狗同时口服和静脉注射该药物及其稳定同位素标记类似物后MK-0462的药代动力学。该实验提供了血浆清除率的估计值，并精确测量了药物的口服生物利用度。液相色谱-串联质谱在定量实验中的日益广泛应用可能会重新激发人们对稳定同位素作为药物研究工具的兴趣。
