title: Identification of the major metabolites of 5-n-butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one, a new angiotensin type 1 receptor antagonist, in rat bile by HPLC-diode array detection-MS and HPLC-MS/MS.
abstract: 5-n-Butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one (1b), a new non-peptide angiotensin type 1 receptor antagonist, has been observed to play a positive role in the treatment of hypertension in preclinical tests. Rats were dosed with the drug, and the major metabolites in the bile were separated by gradient elution high-performance liquid chromatography. HPLC-diode array detection-mass spectrometry, HPLC-electrospray ionization MS/MS methods in negative ion mode and collision-induced dissociation were used to elucidate the structures of the major metabolites of 1b. One dihydroxylated 1b (M1), two monohydoxylated 1b (M2, M3) and one 1b monoglucuronide (M5) were found in male rat bile; however, three monohydoxylated 1b (M2, M3, M4) and one 1b monoglucuronide (M5) were found in female rat bile. These metabolites greatly differ in amount between male and female rat bile.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, No. 24, Tong Jia Xiang Street, Nanjing 210009, People's Republic of China.
authors.forename: Bei
authors.initials: B
authors.lastname: Yan
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
authors.forename: Hua
authors.initials: H
authors.lastname: Lv
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D008297:Male; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013777:Tetrazoles / Q000378:metabolism / Q000493:pharmacokinetics*; D014230:Triazoles / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: C524079:5-n-butyl-4-(4-(2-(1H-tetrazol-5-yl)-1H-pyrrol-1-yl)phenylmethyl)-2,4-dihydro-2-(2,6-dichlorophenyl)-3H-1,2,4-triazol-3-one; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014230:Triazoles