A RAPID AND SPECIFIC ASSAY, BASED ON LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION MASS-SPECTROMETRY, FOR THE DETERMINATION OF MK-434 (A 5-ALPHA-REDUCTASE INHIBITOR) AND ITS METABOLITES IN PLASMA

MK-434 is a new 5alpha-reductase inhibitor. A sensitive and specific a ssay based on combined liquid chromatography-mass spectrometry (LC-MS) has been developed for the determination of this compound in plasma. The analyte was isolated from plasma by solid-phase extraction on a C1 8 cartridge. A related substance, L-654,066, was used as the internal standard. Extracts were separated on a 5-cm C18-reversed-phase high pe rformance liquid chromatography column interfaced via the heated nebul izer probe to a corona discharge chemical ionization source. The mass spectrometer was operated in the positive ion MS-MS mode. The method h ad sufficient sensitivity, precision, accuracy, and selectivity for th e analysis of clinical samples containing MK-434 and its two principal metabolites at concentrations in the range 0.5-50 ng ml-1. The chroma tographic run time was <5 min.