Anizan Sebastien, Ellefsen Kayla, Concheiro Marta, Suzuki Masaki, Rice Kenner C, Baumann Michael H, Huestis Marilyn A
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, USA.
Anal Chim Acta. 2014 May 27;827:54-63. doi: 10.1016/j.aca.2014.04.015. Epub 2014 Apr 12.
Synthetic cathinones are recreational drugs that mimic the effects of illicit stimulants like cocaine, amphetamine or Ecstasy. Among the available synthetic cathinones in the United States, 3,4-methylenedioxypyrovalerone (MDPV) is commonly abused and associated with dangerous side effects. MDPV is a dopamine transporter blocker 10-fold more potent than cocaine as a locomotor stimulant in rats. Previous in vitro and in vivo studies examining MDPV metabolism reported 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) as the two primary metabolites. We developed and validated a liquid chromatography-high resolution mass spectrometry method to quantify MDPV and its primary metabolites in 100 μL human and rat plasma. Plasma hydrolysis was followed by protein precipitation before analysis. Limits of detection were 0.1 μg L(-1), with linear ranges from 0.25 to 1000 μg L(-1). Process efficiency, matrix effect, total imprecision (%CV) and accuracy (%target) were 36-93%, from -8 to 12%, 2.1 to 7.3% and 86 to 109%, respectively. MDPV and metabolites were stable at room temperature for 24 h, 4 °C for 72 h and after 3 freeze-thaw cycles with less than 10% variability. Human-rat plasma cross validation demonstrated that rat plasma could be accurately quantified against a human plasma calibration curve. As proof of this method, rat plasma specimens were analyzed after intraperitoneal and subcutaneous dosing with MDPV (0.5 mg kg(-1)). MDPV, 3,4-catechol-PV and 4-OH-3-MeO-PV concentrations ranged from not detected to 107.5 μg L(-1) prior to and up to 8h after dosing. This method provides a simultaneous quantification of MDPV and two metabolites in plasma with good selectivity and sensitivity.
合成卡西酮是一类娱乐性药物，可模拟可卡因、安非他明或摇头丸等非法兴奋剂的效果。在美国现有的合成卡西酮中，3,4-亚甲基二氧吡咯戊酮（MDPV）常被滥用，并伴有危险的副作用。MDPV是一种多巴胺转运体阻滞剂，作为大鼠运动兴奋剂，其效力比可卡因高10倍。此前关于MDPV代谢的体外和体内研究报告称，3,4-二羟基吡咯戊酮（3,4-儿茶酚-PV）和4-羟基-3-甲氧基吡咯戊酮（4-OH-3-MeO-PV）是两种主要代谢产物。我们开发并验证了一种液相色谱-高分辨率质谱法，用于定量100μL人血浆和大鼠血浆中的MDPV及其主要代谢产物。分析前先进行血浆水解，然后进行蛋白沉淀。检测限为0.1μg L⁻¹，线性范围为0.25至1000μg L⁻¹。方法效率、基质效应、总不精密度（%CV）和准确度（%目标值）分别为36-93%、-8至12%、2.1至7.3%和86至109%。MDPV及其代谢产物在室温下24小时、4℃下72小时以及3次冻融循环后均稳定，变异小于10%。人-大鼠血浆交叉验证表明，大鼠血浆可根据人血浆校准曲线进行准确定量。作为该方法的验证，给大鼠腹腔注射和皮下注射MDPV（0.5mg kg⁻¹）后，对大鼠血浆样本进行分析。给药前至给药后8小时，MDPV、3,4-儿茶酚-PV和4-OH-3-MeO-PV的浓度范围从未检测到至107.5μg L⁻¹。该方法能够同时定量血浆中的MDPV及其两种代谢产物，具有良好的选择性和灵敏度。
