In vitro, in vivo and in silico metabolic profiling of α-pyrrolidinopentiothiophenone, a novel thiophene stimulant

Bioanalysis. 2016;8(1):65-82. doi: 10.4155/bio.15.237. Epub 2015 Dec 9.


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.

Materials & 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.

Results/conclusion: 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.

Keywords: hepatocytes; high-resolution MS; metabolism; novel psychoactive substances; synthetic cathinone; α-PVT.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Central Nervous System Stimulants / metabolism*
  • Central Nervous System Stimulants / urine
  • Computer Simulation*
  • Data Mining
  • Hepatocytes / metabolism
  • Humans
  • Mass Spectrometry
  • Metabolomics / methods*
  • Microsomes, Liver / metabolism
  • Pyrrolidines / metabolism*
  • Pyrrolidines / urine
  • Thiophenes / metabolism*
  • Thiophenes / urine


  • Central Nervous System Stimulants
  • Pyrrolidines
  • Thiophenes
  • alpha-pyrrolidinopentiothiophenone