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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

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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.

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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.

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Authors and Affiliations

  1. Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Antwerp, Belgium

    Noelia Negreira, Claudio Erratico, Alexander L. N. van Nuijs, Hugo Neels & Adrian Covaci

  2. Department of Environmental Sciences, Jozêf Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia

    Tina Kosjek & Ester Heath

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  1. Noelia Negreira
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  2. Claudio Erratico
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  3. Tina Kosjek
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  4. Alexander L. N. van Nuijs
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  5. Ester Heath
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  6. Hugo Neels
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  7. Adrian Covaci
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Correspondence to Adrian Covaci.

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Negreira, N., Erratico, C., Kosjek, T. et al. 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. Anal Bioanal Chem 407, 5803–5816 (2015). https://doi.org/10.1007/s00216-015-8763-6

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  • DOI: https://doi.org/10.1007/s00216-015-8763-6

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