Enzalutamide와 활성대사체의 동시분석법 개발 및 흰쥐에서의 활성대사체 동태 특성 규명

• 영문명: Simultaneous Quantification of Enzalutamide and Its active Metabolite and Characterization of the Kinetics of Active Metabolite in Rats
• 발행기관: 대한약학회
• 저자명: 정종우(Jong-woo Jeong) 구태성(Tae-Sung Koo)
• 간행물 정보: 『약학회지』제62권 제2호(2018년), 63~70쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2018.03.30

국문 초록

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.

목차

실험방법 (Experimental Methods)

결과 및 고찰 (Result and Discussion)

결 론 (Conclusion)

키워드

Enzalutamide N-desmethyl enzalutamide Pharmacokinetics Metabolite LC-MS/MS