Enzalutamide와 활성대사체의 동시분석법 개발 및 흰쥐에서의 활성대사체 동태 특성 규명

Simultaneous Quantification of Enzalutamide and Its active Metabolite and Characterization of the Kinetics of Active Metabolite in Rats

A liquid chromatography–tandem mass spectrometric method was developed for the determination of an anti-prostate cancer drug, enzalutamide (EZT), and its active metabolite, N-desmethyl enzalutamide (NDE), in rat plasma. EZT, NDE and bicalutamide (internal standard; BCT) were extracted with ethyl acetate and separated using a column packed with octadecylsilica (5 μm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase. Detection was accomplished using MS/MS by multiple-reaction monitoring the transitions of m/z 465.1 to 209.2, 451.2 to 195.2 and 431.1 to 217.1 for EZT, NDE and BCT, respectively. The quantifiable range for the plasma samples was confirmed to be from 0.5 to 1,000 ng/ mL, and the all validation values, including the precision (coefficient of variance ≤ 11.80%) and accuracy (relative error ≤ 5.107%) of the measurements, were within the acceptable ranges given by FDA guidelines. The developed analytical method was successfully applied to characterize the kinetics of formation of the active metabolite. Considering EZT is pri-marily eliminated by hepatic metabolism in rats, the formation of NDE accounts for approximately 34% of the overall elim-ination of EZT in rats.