Uralets Victor, Rana Sumandeep, Morgan Stewart, Ross Wayne
Redwood Toxicology Laboratory, 3650 Westwind Boulevard, Santa Rosa, CA 95403, USA.
J Anal Toxicol. 2014 Jun;38(5):233-41. doi: 10.1093/jat/bku021. Epub 2014 Mar 25.
The study of 34,561 urine specimens, submitted for designer stimulant testing between February 2011 and January 2013, provided an opportunity: to estimate the range of synthetic cathinones (SC) abused in the USA, to observe multiple examples of metabolic profiles for each drug in various stages of excretion in human urine, to evaluate the extent of metabolism of specific SC and to select metabolites or parent drugs for routine testing. Sixteen SC were found in random patient samples: buphedrone; butylone; 3,4-dimethylmethcathinone; ethcathinone; N-ethylbuphedrone; ethylone; flephedrone; mephedrone; 4-methylbuphedrone; 3,4-methylenedioxypyrovalerone (MDPV); 4-methyl-N-ethylcathinone; methylone; pentedrone; pentylone; α-pyrrolidinobutiophenone (PBP) and α-pyrrolidinopentiophenone (PVP). After liquid/liquid extraction and trifluoroacetylation, specimens were screened by gas chromatography-mass spectrometry (GC-MS) for drugs and metabolites excreted free in urine. Each SC exhibited a characteristic metabolic profile, as shown by multiple examples. Metabolites' structures were postulated on the basis of their mass spectra. A large group of SC appears to metabolize extensively by carbonyl reduction into respective substituted ephedrines and further by N-dealkylation into norephedrines. Abundant metabolites in this group are essential markers of the parent drug use. Unchanged drugs are far less abundant or not found at all. SC with methylenedioxy attachment to the aromatic ring, metabolize by carbonyl reduction to a much lesser extent and are best detected as such in free urine fraction. PBP and PVP can be detected either unchanged or as metabolites, resulting from pyrrolidine ring degradation into primary amine followed by carbonyl reduction. MDPV appears in urine as such with no apparent free metabolites.
对2011年2月至2013年1月间提交用于新型兴奋剂检测的34561份尿液样本进行的研究提供了一个契机：估计在美国滥用的合成卡西酮（SC）范围；观察每种药物在人尿液排泄不同阶段的多种代谢谱实例；评估特定SC的代谢程度；选择代谢物或母体药物进行常规检测。在随机抽取的患者样本中发现了16种SC：丁丙诺啡；丁酮；3,4-二甲基甲卡西酮；乙卡西酮；N-乙基丁丙诺啡；乙酮；氟丁酮；甲麻黄碱；4-甲基丁丙诺啡；3,4-亚甲基二氧吡咯戊酮（MDPV）；4-甲基-N-乙基卡西酮；甲酮；戊二酮；戊酮；α-吡咯烷基丁苯酮（PBP）和α-吡咯烷基戊苯酮（PVP）。经过液/液萃取和三氟乙酰化后，通过气相色谱-质谱联用（GC-MS）对尿液中游离排泄的药物和代谢物进行样本筛查。如多个实例所示，每种SC都呈现出特征性的代谢谱。代谢物的结构根据其质谱进行推测。一大类SC似乎通过羰基还原广泛代谢为各自的取代麻黄碱，并进一步通过N-脱烷基作用代谢为去甲麻黄碱。该组中丰富的代谢物是母体药物使用的重要标志物。未变化的药物含量要少得多或根本未被发现。与芳环相连有亚甲二氧基的SC，羰基还原代谢程度要小得多，在游离尿液部分中最好这样检测。PBP和PVP既可以原样检测，也可以作为代谢物检测，这是由吡咯烷环降解为伯胺后再进行羰基还原产生的。MDPV原样出现在尿液中，没有明显的游离代谢物。
