title: LC-MS/MS method for the simultaneous determination of Lys-MCC-DM1, MCC-DM1 and DM1 as potential intracellular catabolites of the antibody-drug conjugate trastuzumab emtansine (T-DM1).
abstract: Lysine-MCC-DM1, MCC-DM1 and DM1 are potential catabolites of trastuzumab emtansine (T-DM1). A convenient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to detect these catabolites simultaneously in in vitro investigations for the first time. Protein precipitation was utilized to prepare the samples. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with mobile-phase gradient elution. The calibration curves of each analyte ranging from 1 to 100nM showed good linearity (r2>0.995). The method was validated successfully and applied to the intracellular catabolism and regulation of T-DM1.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ye
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Qianying
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yao
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ni
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address: guangjiwang@hotmail.com.
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address: zhangjw_cnnj@sina.com.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000906:Antibodies / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods; D018796:Immunoconjugates / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D008453:Maytansine / Q000031:analogs & derivatives* / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods; D000068878:Trastuzumab
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D018796:Immunoconjugates; D008453:Maytansine; D008239:Lysine; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine
keywords: Antibody-drug conjugate; Catabolites; LC–MS/MS; T-DM1