Liquid chromatography-tandem mass spectrometry identification of metabolites of two 5-HT1A antagonists, N-{2-[4-(2-methoxylphenyl)piperazino]ethyl}-N-(2-pyridyl) trans- and cis-4-fluorocyclohexanecarboxamide, produced by human and rat hepatocytes

Citation
Y. Ma et al., Liquid chromatography-tandem mass spectrometry identification of metabolites of two 5-HT1A antagonists, N-{2-[4-(2-methoxylphenyl)piperazino]ethyl}-N-(2-pyridyl) trans- and cis-4-fluorocyclohexanecarboxamide, produced by human and rat hepatocytes, J CHROMAT B, 755(1-2), 2001, pp. 47-56
Citations number
10
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF CHROMATOGRAPHY B
ISSN journal
1387-2273 → ACNP
Volume
755
Issue
1-2
Year of publication
2001
Pages
47 - 56
Database
ISI
SICI code
1387-2273(20010505)755:1-2<47:LCMSIO>2.0.ZU;2-1
Abstract
Two 5-HT1A antagonists, t-FCWAY and c-FCWAY, were developed as imaging agen ts for positron emission tomography (PET). In order to evaluate these compo unds, hepatocytes from both human and rat were utilized to produce metaboli tes and LC-MS-MS was used to identify metabolites. These in vitro metabolis m studies indicate that hydrolysis of the amide linkage is the major metabo lism pathway for humans, whereas aromatic ring-oxidation is the major metab olism pathway for rat. The rat hepatocyte results correlate well with in vi vo rat metabolism studies. Based on the structures of the metabolites, we h ave developed an extraction procedure to determine the concentration of the parent compound in plasma. Published by Elsevier Science B.V.