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
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
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.