title: Study of the in vitro metabolism of TJ0711 using ultra high performance liquid chromatography with quadrupole time-of-flight and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry.
abstract: TJ0711 (1-[4-(2-methoxyethyl)phenoxy]-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol) is a novel β-adrenoreceptor blocker with vasodilating activity. The aim of this study was to investigate the in vitro metabolic properties of TJ0711 from both qualitative and quantitative aspects using mouse, rat, dog, and human liver microsomes as well as rat hepatocytes. Two modern liquid chromatography with tandem mass spectrometry systems, ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry, were utilized for the analysis. To better characterize the metabolic pathways of TJ0711, two major metabolites were incubated under the same conditions as that for TJ0711. TJ0711 was extensively metabolized in vitro, and a total of 34 metabolites, including 19 phase I and 15 phase II metabolites, were identified. Similar metabolite profiles were observed among species, and demethylation, hydroxylation, carboxylic acid formation, and glucuronidation were proposed as the major metabolic routes. Significant interspecies differences were observed in the metabolic stability studies of TJ0711. Furthermore, gender differences were significant in mice, rats, and dogs, but were negligible in humans. The valuable information provided in this work will be useful in planning and interpreting further pharmacokinetic, in vivo metabolism and toxicological studies of this novel β-blocker.
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Lei
authors: L
authors: Hu
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Zhenhua
authors: Z
authors: Lv
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Gao
authors: G
authors: Li
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Xiaolong
authors: X
authors: Xu
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Chenghao
authors: C
authors: Zhang
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Peng
authors: P
authors: Cao
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Jiangeng
authors: J
authors: Huang
authors: Department of pharmaceutics, School of pharmacy, Tongji medical college.|Hubei Engineering Research Center for Novel Drug Delivery Systems, Huazhong University of Science and Technology, Wuhan, China.
authors: Luqin
authors: L
authors: Si
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001798:Blood Proteins
keywords: Beta-blockers; Liver microsomes; Metabolism; Quadrupole linear ion trap; Quadrupole time-of-flight