In Vivo Formation of Codeinone-Glutathione Adduct: Isolation and Identification of a New Metabolite in the Bile of Codeine-Treated Guinea Pig

metabolism of morphine, we have established a novel metabolic pathway of morphine which produces morphinone-glutathione adduct (MO-GSH) via MO (14-17). In the present investigation, we demonstrated the formation of codeinone-glutathione adduct (CO-GSH) from codeine in guinea pigs. The metabolite was detected by high-performance liquid chromatography (HPLC), then isolated and identified from the bile. The structures of CO-GSH was unambiguously identified as S-[4,5-epoxy3-methoxy-17-methyl-6-oxo-morphinan-(8S)-yl]glutathione, in comparison with the synthetic authentic CO-GSH by fastatom-bombardment mass spectrometry (FAB-MS) and 500 MHz Fourier-transform-nuclear magnetic resonance (FT-NMR) spectrometric analysis.