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

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Diao, XingxingNational Institute Drug Abuse, MD 21224 USA (författare)

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

Artikel/kapitelEngelska2016

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2016-01-25
SPRINGER,2016
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LIBRIS-ID:oai:DiVA.org:liu-127050
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-127050URI
https://doi.org/10.1208/s12248-016-9867-4DOI

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Språk:engelska
Sammanfattning på:engelska

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

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmaceutical Sciences hsv//eng
FDU-PB-22; FUB-PB-22; hepatocyte metabolism; high-resolution mass spectrometry; synthetic cannabinoid

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Scheidweiler, Karl B.National Institute Drug Abuse, MD 21224 USA (författare)
Wohlfarth, ArianeLinköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden(Swepub:liu)ariwo79 (författare)
Pang, ShaokunSCIEX Ltd, CA 94404 USA (författare)
Kronstrand, RobertLinköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,National Board Forens Med, Department Forens Genet and Forens Toxicol, Sweden(Swepub:liu)robkr41 (författare)
Huestis, Marilyn A.National Institute Drug Abuse, MD 21224 USA (författare)
National Institute Drug Abuse, MD 21224 USAAvdelningen för läkemedelsforskning (creator_code:org_t)

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Ingår i:AAPS Journal: SPRINGER18:2, s. 455-4641550-7416

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Av författaren/redakt...: Diao, Xingxing; Scheidweiler, Ka ...; Wohlfarth, Arian ...; Pang, Shaokun; Kronstrand, Robe ...; Huestis, Marilyn ...

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