Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome RM, Italy.
Rapid Commun Mass Spectrom. 2010 Sep;24(18):2706-14. doi: 10.1002/rcm.4692.
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.
一种用于新设计药物 3,4-亚甲基二氧吡咯戊酮（MDPV）毒理学筛选的方法被描述；重点是其在兴奋剂分析中的应用。使用人肝微粒体和 S9 细胞部分进行 CYP450 相 I 和尿苷 5'-二磷酸葡萄糖醛酸转移酶（UGT）和磺基转移酶（SULT）相 II 代谢研究，评估了 MDPV 的代谢。随后使用液/液提取将产生的代谢物提取出来，并使用气相色谱/质谱（GC/MS）作为三甲基硅烷基（TMS）衍生物进行分析。通过使用液相色谱/四极杆飞行时间（LC/QTOF）质谱仪进行精确质量测量，进一步确认了代谢物的结构。研究表明，MDPV 的主要代谢物是儿茶酚和甲基儿茶酚吡咯戊酮，它们又被硫酸化和葡糖醛酸化。通过评估检测限和定量限、线性、重复性和准确性，对尿液中 MDPV 的测定方法进行了全面验证。该验证表明，该方法适用于兴奋剂和法医毒理学目的的这种兴奋剂物质的筛选。
