Metabolite identification of a new antitumor agent icotinib in rats using liquid chromatography/tandem mass spectrometry.
Rapid Commun Mass Spectrom
; 22(14): 2176-84, 2008 Jul.
Article
en En
| MEDLINE
| ID: mdl-18536068
ABSTRACT
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/MS(n)) 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinazolinas
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Cromatografía Liquida
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Éteres Corona
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Espectrometría de Masas en Tándem
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Antineoplásicos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2008
Tipo del documento:
Article