HPLCを用いたエンザルタミドおよびその活性代謝物の血漿中濃度測定系の確立

抄録

Enzalutamide is an orally administered drug that effectively treats castration-resistant prostate cancer. The prescribed dose of enzalutamide in Japan is the same as that in other countries, possibly causing an overdose of enzalutamide and adverse drug reactions (ADRs) in Japanese patients. In the present study, for the pharmacokinetic study to investigate the relationship between the effectiveness/ADRs and the concentrations of enzalutamide, we developed a method to measure plasma concentrations of enzalutamide and its main active metabolite (N-desmethyl enzalutamide) using high performance liquid chromatography (HPLC). The HPLC-UV system used was Shimadzu LC-20Avp equipped with a 5C18 column using 20 mM ammonium acetate (pH 5.0) containing 43％ acetonitrile as the mobile phase. Enzalutamide and N-desmethyl enzalutamide were detected at 237 nm. Plasma samples were deproteinized by adding acetonitrile containing an internal standard substance (IS), nilutamide. After the centrifugation, the supernatant was collected and evaporated to dryness under a stream of nitrogen gas. The residue was reconstituted with the mobile phase and injected into the HPLC system. Peaks of IS, N-desmethyl enzalutamide and enzalutamide were detected at a retention time of 9.5, 12.7 and 16.8 min, respectively. The established method was validated based on FDA guidelines and found to have good linearity (0.25-25 μg/mL), precision and accuracy. We also confirmed that our method was applicable to the measurement of patient plasma. These results suggest that the established method would be suitable to measure enzalutamide and N-desmethyl enzalutamide in plasma for the research to promote the proper use of enzalutamide.