Journal
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
Volume 22, Issue 14, Pages 2176-2184Publisher
JOHN WILEY & SONS LTD
DOI: 10.1002/rcm.3599
Keywords
-
Ask authors/readers for more resources
Icotinib, 4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-4-quinazoline, is a new antitumor agent. The metabolic pathway of icotinib in rats was studied using liquid chromatography/tandem mass spectrometry (LC/MSn) analysis. Full scan and selected ion monitoring modes were used to profile the possible metabolites of icotinib in rat urine, feces and bile samples. Four phase I metabolites (M1-M4) and two phase II metabolites (M5, M6) were detected and characterized. Multiple-stage mass spectrometry and nuclear magnetic resonance (NMR) spectrometry were employed to elucidate structures of metabolites. Icotinib was metabolized to open the crown ether ring to form the main phase I metabolites. During metabolism, a reactive metabolite was formed. Using semicarbazide as a trapping agent, an intermediate arising from opening of the crown ether ring was detected as an aldehyde product by LC/MS/MS. These data indicated that ring opening of the crown ether was triggered by hydroxylation at the 8 ''-position of the ring to form a hemiacetal intermediate, which was further oxidized or reduced. Finally, the metabolic pathway of icotinib in rats was proposed. Copyright (C) 2008 John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available