Interspecies metabolic diversity of harmaline and harmine in in vitro 11 mammalian liver microsomes.
The β-carboline alkaloids harmaline and harmine are widely present in hallucinogenic plants with great potential for treating depression, Parkinsons disease, and Alzheimers disease. The present study was to elucidate metabolic difference of harmaline and harmine in 11 mammalian liver microsomes in order to quantitate species-specific metabolic profiles. Using the probe substrate reaction, the enzymatic activities for 8 CYP450 isozymes of 11 liver microsomes were characterized. Combining ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS) and ultra performance liquid chromatography combined with electrospray ionization quadrupole tandem mass spectrometry (UPLC-ESI-MSMS) methods, 18 metabolites for harmaline and 11 for harmine were identified. The metabolism patterns differences of them presented discrepancy in the quality and quantity of metabolites. It was notable that O-sulfate conjugation was detected in all species except sheep. The intrinsic clearance CL