Targeted and non‐targeted metabolite identification of MAM‐2201 in human,mouse, and rat hepatocytes |
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| Authors: | Ju‐Hyun Kim Tae Yeon Kong Ju‐Yeon Moon Kyung Ho Choi Yong‐Yeon Cho Han Chang Kang Joo Young Lee Hye Suk Lee |
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| Affiliation: | 1. BK21 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;2. Department of Pharmacology, College of Medicine, Dongguk University, Gyeongju, Republic of Korea;3. Department of Emergency Medicine, Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea |
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| 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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| Keywords: | Hepatocytes LC– HRMS MAM‐2201 metabolite profiling metabolomics approach |
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