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Analytical and Bioanalytical Chemistry

, Volume 407, Issue 19, pp 5803–5816 | Cite as

In vitro Phase I and Phase II metabolism of α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol

  • Noelia Negreira
  • Claudio Erratico
  • Tina Kosjek
  • Alexander L. N. van Nuijs
  • Ester Heath
  • Hugo Neels
  • Adrian Covaci
Research Paper

Abstract

The aim of the present study was to identify the in vitro Phase I and Phase II metabolites of three new psychoactive substances: α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV), and methedrone, using human liver microsomes and human liver cytosol. Accurate-mass spectra of metabolites were obtained using liquid chromatography-quadrupole time-of-flight mass spectrometry. Six Phase I metabolites of α-PVP were identified, which were formed involving reduction, hydroxylation, and pyrrolidine ring opening reactions. The lactam compound was the major metabolite observed for α-PVP. Two glucuronidated metabolites of α-PVP, not reported in previous in vitro studies, were further identified. MDPV was transformed into 10 Phase I metabolites involving reduction, hydroxylation, and loss of the pyrrolidine ring. Also, six glucuronidated and two sulphated metabolites were detected. The major metabolite of MDPV was the catechol metabolite. Methedrone was transformed into five Phase I metabolites, involving N- and O-demethylation, hydroxylation, and reduction of the ketone group. Three metabolites of methedrone are reported for the first time. In addition, the contribution of individual human CYP enzymes in the formation of the detected metabolites was investigated.

Keywords

Cathinones Quadrupole time-of-flight mass spectrometry In vitro metabolism MDPV Methedrone α-PVP New psychoactive substances 

Notes

Acknowledgments

The authors thank Walid Maho and Steven Andries for technical assistance. This study was financially supported by the EU through the FP7 (2007-2013) project under grant agreement no. 316665 (A-TEAM). N.N. and A.L.N.vN. acknowledge University of Antwerp and FWO Flanders for their respective postdoctoral fellowships.

Supplementary material

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ESM 1 (PDF 1747 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Noelia Negreira
    • 1
  • Claudio Erratico
    • 1
  • Tina Kosjek
    • 2
  • Alexander L. N. van Nuijs
    • 1
  • Ester Heath
    • 2
  • Hugo Neels
    • 1
  • Adrian Covaci
    • 1
  1. 1.Toxicological Center, Department of Pharmaceutical SciencesUniversity of AntwerpWilrijkBelgium
  2. 2.Department of Environmental SciencesJozêf Stefan InstituteLjubljanaSlovenia

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