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AAPS J. 2016 Mar;18(2):455-64. doi: 10.1208/s12248-016-9867-4. Epub 2016 Jan 25.

In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22.

Author information

1
Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200 Room 05A721, Baltimore, Maryland, 21224, USA.
2
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758, Linköping, Sweden.
3
Department of Drug Research, University of Linköping, 58185, Linköping, Sweden.
4
SCIEX, Redwood City, California, 94404, USA.
5
Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200 Room 05A721, Baltimore, Maryland, 21224, USA. mhuestis@intra.nida.nih.gov.

Abstract

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 μM FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 μM 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 β-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 same metabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after β-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.

KEYWORDS:

FDU-PB-22; FUB-PB-22; hepatocyte metabolism; high-resolution mass spectrometry; synthetic cannabinoid

PMID:
26810398
PMCID:
PMC4779098
DOI:
10.1208/s12248-016-9867-4
[Indexed for MEDLINE]
Free PMC Article

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