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 5 alpha-reductase inhibitor. A sensitive and specific assay 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 C18 cartridge. A related substance, L-654,066, was used as the internal standard. Extracts were separated on a 5-cm C18-reversed-phase high performance liquid chromatography column interfaced via the heated nebulizer probe to a corona discharge chemical ionization source. The mass spectrometer was operated in the positive ion MS-MS mode. The method had sufficient sensitivity, precision, accuracy, and selectivity for the analysis of clinical samples containing MK-434 and its two principal metabolites at concentrations in the range 0.5-50 ng ml-1. The chromatographic run time was < 5 min.
Olah
T V
TV
Merck Research Laboratories, West Point, PA 19486.
Gilbert
J D
JD
Barrish
A
A
Greber
T F
TF
McLoughlin
D A
DA
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D018120:Finasteride / Q000031:analogs & derivatives* / Q000097:blood; D013058:Mass Spectrometry; D011863:Radioimmunoassay; D012015:Reference Standards; D015203:Reproducibility of Results
C088478:17 beta-benzoyl-4-aza-5 alpha-androst-1-ene-3-one; D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; C090503:L 694579; C077586:(5alpha)-23-methyl-4-aza-21-norchol-1-ene-3,20-dione; D018120:Finasteride