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First metabolic profile of PV8, a novel synthetic cathinone, in human hepatocytes and urine by high-resolution mass spectrometry
NIDA, USA; University of Maryland, USA.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. NIDA, USA; National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden.
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2016 (English)In: Analusis, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 408, no 18, 4845-4856 p.Article in journal (Refereed) PublishedText
Abstract [en]

Novel psychoactive substances (NPS) are ever changing on the drug market, making it difficult for toxicology laboratory methods to stay current with so many new drugs. Recently, PV8, a synthetic pyrrolidinophenone, was detected in seized products in Japan (2013), The Netherlands (2014), and Germany (2014). There are no controlled PV8 administration studies, and no pharmacodynamic and pharmacokinetic data. The objective was to determine PV8s metabolic stability in human liver microsome (HLM) incubation and its metabolism following human hepatocyte incubation and high-resolution mass spectrometry (HRMS) with a Thermo Scientific Q-Exactive. Data were acquired with a full-scan data-dependent mass spectrometry method. Scans were thoroughly data mined with different data processing algorithms and analyzed in WebMetaBase. PV8 exhibited a relatively short 28.8 min half-life, with an intrinsic 24.2 mu L/min/mg microsomal clearance. This compound is predicted to be an intermediate clearance drug with an estimated human 22.7 mL/min/kg hepatic clearance. Metabolic pathways identified in vitro included: hydroxylation, ketone reduction, carboxylation, N-dealkylation, iminium formation, dehydrogenation, N-oxidation, and carbonylation. The top three in vitro metabolic pathways were di-hydroxylation amp;gt; ketone reduction amp;gt; gamma-lactam formation. Authentic urine specimen analyses revealed the top three metabolic pathways were aliphatic hydroxylation amp;gt; ketone reduction + aliphatic hydroxylation amp;gt; aliphatic carboxylation, although the most prominent peak was parent PV8. These data provide useful urinary metabolite targets (aliphatic hydroxylation, aliphatic hydroxylation + ketone reduction, aliphatic carboxylation, and di-hydroxylation) for forensic and clinical testing, and focus reference standard companies synthetic efforts to provide commercially available standards needed for PV8 biological specimen testing.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG , 2016. Vol. 408, no 18, 4845-4856 p.
Keyword [en]
PV8; Novel psychoactive substances; Metabolic profiling; HRMS; Hepatocytes; Synthetic cathinones
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:liu:diva-130414DOI: 10.1007/s00216-016-9599-4ISI: 000378999500004PubMedID: 27185540OAI: diva2:952654

Funding Agencies|National Institute on Drug Abuse, National Institutes of Health

Available from: 2016-08-15 Created: 2016-08-05 Last updated: 2016-08-22

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Wohlfarth, ArianeKronstrand, Robert
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