title: A liquid chromatography/positive ion tandem mass spectrometry method for the determination of cilazapril and cilazaprilat in human plasma.
abstract: A simple, rapid, and sensitive high-performance liquid chromatography (HPLC)-electrospray ionization (ESI) tandem mass spectrometric method (LC-MS/MS) has been developed for simultaneous determination of cilazapril levels and its active metabolite, cilazaprilat, in human plasma using enalapril as internal standard. The acquisition was performed in the multiple reaction monitoring mode; monitoring the transitions: m/z 418.4>211.1 for cilazapril and m/z 390.3>211.1 for cilazaprilat. The method involves a simple single-step liquid-liquid extraction with ethyl acetate. The analyte was chromatographed on an YMC C(8) reversed-phase chromatographic column by isocratic elution with 10mM ammonium formate buffer-methanol (10:90, v/v; pH 3.2 with formic acid). Numerous compounds did not interfere with specific multiple reaction monitoring in tandem mass spectrometric detection following C(8) reversed-phase chromatographic separation under conditions that eluted cilazapril, cilazaprilat, and enalapril within 2min. This method was validated over 0.1-500ng ml(-1) of cilazapril and 0.5-50ng ml(-1) of cilazaprilat. Cilazapril and cilazaprilat were stable in standard solution and in plasma samples under typical storage and processing conditions. The assay was successfully applied to a pharmacokinetic study of cilazapril given as a single oral dose (5mg) to healthy volunteers.
authors.affiliation: College of Pharmacy, Kyung Hee University, Hoegi-Dong, Dongdaemun-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Heon-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Wan-Su
authors.initials: WS
authors.lastname: Park
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Cho
authors.forename: Min-Hwan
authors.initials: MH
authors.lastname: Kim
authors.forename: Ji-Hyung
authors.initials: JH
authors.lastname: Seo
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Kim
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.forename: Yong-Sup
authors.initials: YS
authors.lastname: Lee
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee