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Published on: July 29, 2016
Targeted and non-targeted metabolite identification of MAM-2201 in human, mouse, and rat hepatocytes
Ju-Hyun Kim1,2, Tae Yeon Kong1, Ju-Yeon Moon1
1BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
Abstract:
MAM-2201 is a fluorinated naphthoylindole synthetic cannabinoid with potent psychoactive properties that has been detected as an active ingredient in herbal incense blends. To gain a greater understanding of MAM-2201 metabolism and to compare its metabolic fate in humans with those in animals, the metabolism of MAM-2201 in human, mouse, and rat hepatocytes was investigated using liquid chromatography-high-resolution mass spectrometry combined with targeted and non-targeted metabolite profiling approaches. Nineteen phase I metabolites (M1-M19) reported previously in human liver microsomes and 13 novel metabolites were identified in human, mouse, and rat hepatocytes: 1 phase I metabolite (M20) and 12 phase II metabolites including 6 glucuronides (G1-G6), 1 sulfate (S1), and 5 glutathione (GSH) conjugates (GS1-GS5) of MAM-2201 metabolites. G3 was human-specific, but M20, G1, G2, and 5 GSH conjugates were rat-specific, indicating species-related differences in MAM-2201 metabolism. The findings in the present study can be useful for the experimental design and assessment of metabolism-mediated toxic risk of MAM-2201.
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