title: Toxicological determination and in vitro metabolism of the designer drug methylenedioxypyrovalerone (MDPV) by gas chromatography/mass spectrometry and liquid chromatography/quadrupole time-of-flight mass spectrometry.
abstract: A method for the toxicological screening of the new designer drug methylenedioxypyrovalerone (MDPV) is described; with an emphasis on its application for anti-doping analysis. The metabolism of MDPV was evaluated in vitro using human liver microsomes and S9 cellular fractions for CYP450 phase I and uridine 5'-diphosphoglucuronosyltransferase (UGT) and sulfotransferase (SULT) phase II metabolism studies. The resulting metabolites were subsequently liquid/liquid extracted and analyzed using gas chromatography/mass spectrometry (GC/MS) as trimethylsilyl (TMS) derivatives. The structures of the metabolites were further confirmed by accurate mass measurement using a liquid chromatography/quadrupole time-of-flight (LC/QTOF) mass spectrometer. The studies demonstrated that the main metabolites of MDPV are catechol and methyl catechol pyrovalerone, which are in turn sulfated and glucuronated. The method for the determination of MDPV in urine has been fully validated by assessing the limits of detection and quantification, linearity, repeatability, and accuracy. This validation demonstrates the suitability for screening of this stimulant substance for anti-doping and forensic toxicology purposes.
authors.affiliation: Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome RM, Italy. sabina.stranorossi@gmail.com
authors.forename: Sabina
authors.initials: S
authors.lastname: Strano-Rossi
authors.forename: Amy B
authors.initials: AB
authors.lastname: Cadwallader
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Torre
authors.forename: Francesco
authors.initials: F
authors.lastname: Botrè
mesh_terms: D052117:Benzodioxoles / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D002396:Catechols / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D002460:Cell Line; D002853:Chromatography, Liquid / Q000379:methods*; D015198:Designer Drugs / Q000737:chemistry* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D005965:Glucuronates / Q000737:chemistry / Q000378:metabolism; D006139:Guaiacol / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D002396:Catechols; D015198:Designer Drugs; D005965:Glucuronates; D011759:Pyrrolidines; D013431:Sulfates; D006139:Guaiacol; C034221:catechol; C005719:pyrovalerone; D000094982:Synthetic Cathinone