The aim of this study was to identify and characterize the metabolites of OPA generated in the liver microsomes and hepatocytes of rats and humans.
Methods:The metabolites were generated by incubating OPA (5 μM) with liver microsomes or hepatocytes at 37 C. To trap the reactive metabolites, glutathione (GSH, 5mM) was added into microsomal incubations. The metabolite identification and profiling were performed using ultra-high-performance liquid chromatography combined with photo-diode array detector and quadrupole time-of-flight tandem mass spectrometry (LC-Q/TOF-MS). The acquired mass data were processed by MetaboLynx software. The structures of the metabolites were tentatively characterized in terms of their accurate masses, product ions, and retention times.Results: Under the present conditions, a total of nine metabolites were detected and their structures were tentatively identified. Among these metabolites, M8 (OPA catechol) was the most abundant metabolite both in rat and human liver microsomes. M7 (glucuronidation product of M8) was the major metabolite both in rat and human hepatocytes. The metabolic pathways of OPA include demethylenation, dehydrogenation, hydroxylation, methylation and glucuronidation and GSH conjugation.
Conclusion:Our results provided valuable information regarding the in vitro metabolism of OPA, which would help us understand the mechanism of the elimination of OPA and in turn the effectiveness and potential toxicity.
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