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In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22
National Institute Drug Abuse, MD 21224 USA.
National Institute Drug Abuse, MD 21224 USA.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
SCIEX Ltd, CA 94404 USA.
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2016 (English)In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 18, no 2, 455-464 p.Article in journal (Refereed) PublishedText
Abstract [en]

In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB-22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 mu M FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 mu M was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU-PB-22 and FUB-PB-22 positive cases were analyzed after beta-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB-22 and FUB-PB-22 yielded the samemetabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after beta-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake.

Place, publisher, year, edition, pages
SPRINGER , 2016. Vol. 18, no 2, 455-464 p.
Keyword [en]
FDU-PB-22; FUB-PB-22; hepatocyte metabolism; high-resolution mass spectrometry; synthetic cannabinoid
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-127050DOI: 10.1208/s12248-016-9867-4ISI: 000371977400019PubMedID: 26810398OAI: oai:DiVA.org:liu-127050DiVA: diva2:919394
Note

Funding Agencies|Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health

Available from: 2016-04-13 Created: 2016-04-13 Last updated: 2016-04-28

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Wohlfarth, ArianeKronstrand, Robert
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