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First metabolic pro...
First metabolic profile of PV8, a novel synthetic cathinone, in human hepatocytes and urine by high-resolution mass spectrometry
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- Swortwood, Madeleine J. (author)
- NIDA, USA
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- Ellefsen, Kayla N. (author)
- NIDA, USA; University of Maryland, USA
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- Wohlfarth, Ariane (author)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,NIDA, USA; National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden
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- Diao, Xingxing (author)
- NIDA, USA
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- Concheiro-Guisan, Marta (author)
- NIDA, USA; CUNY John Jay Coll Criminal Justice, NY 10019 USA
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- Kronstrand, Robert (author)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden
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- Huestis, Marilyn A. (author)
- NIDA, USA; University of Maryland Baltimore, USA
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(creator_code:org_t)
- 2016-05-16
- 2016
- English.
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In: Analytical and Bioanalytical Chemistry. - : SPRINGER HEIDELBERG. - 1618-2642 .- 1618-2650. ; 408:18, s. 4845-4856
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- PV8; Novel psychoactive substances; Metabolic profiling; HRMS; Hepatocytes; Synthetic cathinones
Publication and Content Type
- ref (subject category)
- art (subject category)
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