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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
Author(s) -
Yan Bei,
Wang Guangji,
Sun Jianguo,
Li Xiaoyu,
Zheng Yuanting,
Ai Hua,
Lv Hua,
Wu Xiaoming,
Xu Jinyi
Publication year - 2007
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.822
Subject(s) - chemistry , chromatography , high performance liquid chromatography , mass spectrometry , electrospray ionization , tetrazole , stereochemistry
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. Copyright © 2007 John Wiley & Sons, Ltd.