In vitro metabolism of new synthetic cannabinoid SDB-006 in human hepatocytes by high-resolution mass spectrometry
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The drug abuse epidemic within the United States remains one of the nation’s most serious social challenges, especially among adolescents and young adults. Novel psychoactive substances continuously emerge into the illicit drugs-of-abuse market to evade legislation. In 2013, SDB-006 was detected as a novel synthetic cannabinoid (SC) with high binding affinity to CB1 (EC50 = 19 nM) and CB2 (EC50 = 134 nM). Unfortunately, no human metabolism data for SDB-006 are currently available, making it challenging to confirm intake, since all previously investigated SCs were extensively metabolized. The present study aims to recommend appropriate marker metabolites for documenting SDB-006 consumption by investigating its metabolism in human hepatocytes. For metabolite profiling, 10 µM of SDB-006 was incubated in human hepatocytes for 3 h. Metabolite identification in hepatocyte samples was accomplished with high-resolution mass spectrometry via information-dependent data acquisition. Results revealed that SDB-006 was highly metabolized in human hepatocytes. A total of 20 metabolites were characterized, generated mainly from hydroxylation and glucuronidation. Hydroxylation occurred primarily on several positions of the pentyl chain. N-Dealkylation was the other major pathway, including depentylation and debenzylation. Based on our data, we propose 4′-keto-SDB-006 (M19) and pentyl-OH-SDB-006 (M15) as optimal marker metabolites for documenting SDB-006 intake.
KeywordsSDB-006 Synthetic cannabinoid Novel psychoactive substance Human hepatocyte metabolism High-resolution mass spectrometry
This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. SDB-006 was generously donated by the US Drug Enforcement Administration.
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Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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