title: 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.
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.
authors.affiliation: Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Antwerp, Belgium.
authors.forename: Noelia
authors.initials: N
authors.lastname: Negreira
authors.forename: Claudio
authors.initials: C
authors.lastname: Erratico
authors.forename: Tina
authors.initials: T
authors.lastname: Kosjek
authors.forename: Alexander L N
authors.initials: AL
authors.lastname: van Nuijs
authors.forename: Ester
authors.initials: E
authors.lastname: Heath
authors.forename: Hugo
authors.initials: H
authors.lastname: Neels
authors.forename: Adrian
authors.initials: A
authors.lastname: Covaci
mesh_terms: D052117:Benzodioxoles / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D011427:Propiophenones / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D003580:Cytochromes; D011427:Propiophenones; D011759:Pyrrolidines; C542924:alpha-pyrrolidinovalerophenone; C558328:4-methoxymethcathinone; D000094982:Synthetic Cathinone