title: In vitro, in vivo and in silico metabolic profiling of α-pyrrolidinopentiothiophenone, a novel thiophene stimulant.
abstract: BACKGROUND
  Little or no pharmacological or toxicological data are available for novel psychoactive substances when they first emerge, making their identification and interpretation in biological matrices challenging.
  
  
  METHODS
  A new synthetic cathinone, α-pyrrolidinopentiothiophenone (α-PVT), was incubated with hepatocytes and samples were analyzed using liquid chromatography coupled to a Q Exactive™ Orbitrap mass spectrometer. Authentic urine specimens from suspected α-PVT cases were also analyzed. Scans were data mined with Compound Discoverer™ for identification and structural elucidation of metabolites.
  
  
  CONCLUSIONS
  Seven α-PVT metabolites were identified in hepatocyte incubations, and in the authentic urine samples, also with an additional monohydroxylated product and a glucuronide of low intensity. α-PVT dihydroxypyrrolidinyl, α-PVT 2-ketopyrrolidinyl, α-PVT hydroxythiophenyl and α-PVT thiophenol had the most intense in vivo signals.
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Swortwood
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Carlier
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.|Program in Toxicology, University of Maryland Baltimore, Baltimore, MD 21201, USA.
authors.forename: Kayla N
authors.initials: KN
authors.lastname: Ellefsen
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.|National Board of Forensic Medicine, Linköping, Sweden.
authors.forename: Ariane
authors.initials: A
authors.lastname: Wohlfarth
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Diao
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.|Department of Sciences, John Jay College of Criminal Justice, City University of New York, New York, NY 10019, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Concheiro-Guisan
authors.affiliation: Department of Forensic Genetics & Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.|Department of Medical & Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Kronstrand
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000697:Central Nervous System Stimulants / Q000378:metabolism* / Q000652:urine; D003198:Computer Simulation; D057225:Data Mining; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism* / Q000652:urine; D013876:Thiophenes / Q000378:metabolism* / Q000652:urine
chemical_list: D000697:Central Nervous System Stimulants; D011759:Pyrrolidines; D013876:Thiophenes; C000610986:alpha-pyrrolidinopentiothiophenone
keywords: hepatocytes; high-resolution MS; metabolism; novel psychoactive substances; synthetic cathinone; α-PVT