QUANTITATION OF THE 5HT(1D) AGONISTS MK-462 AND SUMATRIPTAN IN PLASMABY LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION MASS-SPECTROMETRY

The 5HT(1D) agonist sumatriptan is efficacious in the treatment of mig raines. MK-462 is a drug of the same class which is under development in our laboratories. Bioanalytical methods of high efficiency, specifi city and sensitivity were required to support the preclinical and clin ical programs. These assays were based on HPLC with tandem MS-MS detec tion. MK-462 acid sumatriptan were extracted using an automated solid- phase extraction technique on a C-2 Varian Bond-Elut cartridge. The n- diethyl analogues of MK-462 and sumatriptan were used as internal stan dards. The analytes were chromatographed using reversed-phase (nitrile ) columns coupled via a heated nebulizer interface to an atmospheric p ressure chemical ionization source. The chromatographic run times were less than 7 min. Both methods were precise, accurate and selective do wn to plasma concentrations of 0.5 ng/ml. The assay for MK-462 was ada pted to separately monitor the unlabeled and C-14-labeled species of t he drug following intravenous administration of radiolabeled material to man.