Identification and structure characterization of two unknown impurities in TJ0711 HCl active pharmaceutical ingredient,a novel α1/β1 receptor-blocking agent
1-”4-(2-Methoxyethyl) phenoxy”-3-””2-(2-methoxyphenoxy) ethyl”amino”-2-propanol hydrochloride(TJ0711 HC1), a new α1/β 1 receptor-blocking agent, has been found to be effective in the treatment of hypertension in preclinical tests.Two low-level impurities of the order of 0.05% were detected by high performance liquid chromatography (HPLC) method.These two impurities were marked as Imp-1 and Imp-2.The unknown impurities were identified by liquid chromatography-tandem mass spectrometry using electrospray ionization source and Q-trap mass analyzer (LC-ESI-QT/MS/MS).Based on LC-MS/MS data and the background knowledge of the synthetic scheme of TJ0711 HC1, the structures of Imp-1 and Imp-2 were proposed to be 1-”4-(2-Hydroxyethyl)-phenoxy”-3-”2-(2-methoxy-phenoxy)-ethylamino”-2-propanol and 4-”2-Hydroxy-3-”2-(2-methoxy-phenoxy)-ethylamino”-propoxy ”-benzaldehyde respectively.Structure confirmation of these two impurities was unambiguously carried out by independent synthesis followed by characterization using mass spectrometry (MS), high resolution mass spectrometry(HRMS) and nuclear magnetic resonance(NMR).
TJ0711 HC1 Impurity profile LC-MS/MS HRMS NMR
Xiaolong Xu Jiangeng Huang Gao Li Luqin Si
Department of Pharmaceutics, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
国内会议
2013年中国药物制剂大会——中国药学会药剂专业委员会2013年学术年会暨国际控释协会中国分会2013年学术年会
武汉
英文
422-425
2013-10-26（万方平台首次上网日期，不代表论文的发表时间）