The metabolomics of (±)-arecoline 1-oxide in the mouse and its formation by human flavin-containing monooxygenases.
This paper combines the disciplines of multivariate statistics (as applied in metabolomic studies) with drug metabolite structure elucidation to detect and identify metabolites of the areca gum alkaloid, arecoline. The N-oxide of arecoline was administered to mice and urine analysed by UPLC-TOFMS. Mass chromatograms (m/z range 100 - 950) were analysed by PCS and PLS-DA to identify ions specific to the treated animals as a first step in identifying metabolites. MS/MS experiments were then performed to further elucidate the metabolite structures. The study also included some in vitro enzymology with recombinant P450 and FMOs. Various mercapturate metabolites were identified from the down stream metabolism of glutathione conjugates, with evidence of involvement of the methylthiol shunt.