Quantification and pharmacokinetic study of tumor-targeting agent MHI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry

作     者：Zhijun Wang Bogdan Z.Olenyuk Jean Chen Shih Jeffrey Wang 

作者机构：Center for Advancement of Drug Research and Evaluation College of Pharmacy Western University of Health Sciences Department of Pharmaceutical Sciences College of Pharmacy Marshall B.Ketchum University Department of Pharmacology and Pharmaceutical Sciences School of Pharmacy Department of Cell and Neurobiology Keck School of Medicine USC-Taiwan Center for Translational Research University of Southern California Department of Pharmaceutical Sciences College of Pharmacy Western University of Health Sciences 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2018年第8卷第3期

页      面：153-159页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 070302[理学-分析化学] 0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 0702[理学-物理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by USC-Taiwan Center for Translational Research the Daniel Tsai Family Fund Boyd & Elsie Welin Professorship by the Department of Defense Prostate Cancer Research Program Grant W81XWH-12-1-0282 

主　　题：MH1148-clorgyline HPLC Mass spectrometry Pharmacokinetics 

摘      要：A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- ESI-MS/MS） method was developed for the quantification of MHl148-clorgyline amide （NMl-amide）, a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMl-amide in mice following intravenous administration. NMl-amide together with the internal standard （IS）, MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMl-amide by detecting m/z transition of 491.2-361.9, and 685.3-258.2 for NMl-amide and the IS, respectively. The lower limit of quantification （LLOQ） of the HPLC- MS/MS method for NMl-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2〉 0.99 in the concentration range of 0.005-2μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMl-amide.