In vitro metabolism of new synthetic cannabinoid SDB-006 in human hepatocytes by high-resolution mass spectrometry

摘要: The drug abuse epidemic within the United States remains one of nation’s most serious social challenges, especially among adolescents and young adults. Novel psychoactive substances continuously emerge into illicit drugs-of-abuse market to evade legislation. In 2013, SDB-006 was detected as a novel synthetic cannabinoid (SC) with high binding affinity CB1 (EC50 = 19 nM) CB2 (EC50 = 134 nM). Unfortunately, no human metabolism data for are currently available, making it challenging confirm intake, since all previously investigated SCs were extensively metabolized. present study aims recommend appropriate marker metabolites documenting consumption by investigating its in hepatocytes. For metabolite profiling, 10 µM incubated hepatocytes 3 h. Metabolite identification hepatocyte samples accomplished high-resolution mass spectrometry via information-dependent acquisition. Results revealed that highly metabolized A total 20 characterized, generated mainly from hydroxylation glucuronidation. Hydroxylation occurred primarily on several positions pentyl chain. N-Dealkylation other major pathway, including depentylation debenzylation. Based our data, we propose 4′-keto-SDB-006 (M19) pentyl-OH-SDB-006 (M15) optimal intake.