Detection of the recently emerged synthetic cannabinoid 5F-MDMB-PICA in "legal high' products and human urine samples
Detection of the recently emerged synthetic cannabinoid 5F-MDMB-PICA in "legal high' products and human urine samples
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DOI：
10.1002/dta.2201
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发表时间：
2018-01-01
影响因子：
2.9
通讯作者：
Auwaerter, Volker
中科院分区：
文献类型：
--
作者：
Mogler, Lukas;Franz, Florian;Auwaerter, Volker
吲哚或吲唑类合成大麻素（SC）带有缬氨酸或叔亮氨酸的取代基，是一种经常被滥用的新精神活性物质。5 F-MDMB-PICA（N-{[1-（5-氟戊基）-1H-吲哚-3-基]羰基}-3-甲基缬氨酸甲酯）在德国药品市场上的出现是在科学研究背景下合成的物质被秘密实验室滥用的又一个例子，将其添加到法律的“高”产品中。本文采用气相色谱-质谱联用（GC-MS）技术对几种法律的高纯度产品中的5 F-MDMB-PICA进行了检测。为了通过尿液分析检测适合证明5 F-MDMB-PICA消耗的特征代谢物，使用液相色谱-串联质谱（LC-MS/MS）和液相色谱四极杆飞行时间质谱（LC-QToF-MS）技术进行合并人肝微粒体（pHLM）试验并进行评价，以生成体外I相代谢物的参比光谱。通过分析20多份真实的人尿液样本来研究体内I相代谢，并与从pHLM测定中收到的数据进行比较。5-氟戊基侧链的生物转化和末端甲酯键的水解是主要的I相生物转化步骤。将通过甲酯水解或吲哚环系统单羟基化形成的两种已鉴别的主要代谢产物作为适当的尿液生物标志物进行评价，并就分析结果的解释进行讨论。对一份尿样进行的5 F-MDMB-PICA II相代谢物的示例性分析显示，两种主要的I相代谢物在肾脏排泄前发生了广泛的葡萄糖醛酸化。因此，缀合物裂解对于提高灵敏度是合理的。市售的尿液免疫化学预检测被证明不适合检测5 F-MDMB-PICA消耗。版权所有（c）2017约翰威利父子有限公司
Indole or indazole-based synthetic cannabinoids (SCs) bearing substituents derived from valine or tert-leucine are frequently abused new psychoactive substances (NPS). The emergence of 5F-MDMB-PICA (methyl N-{[1-(5-fluoropentyl)-1H-indol-3-yl]carbonyl}-3-methylvalinate) on the German drug market is a further example of a substance synthesized in the context of scientific research being misused by clandestine laboratories by adding it to legal high' products. In this work, we present the detection of 5F-MDMB-PICA in several legal high products by gas chromatography-mass spectrometry (GC-MS) analysis. To detect characteristic metabolites suitable for a proof of 5F-MDMB-PICA consumption by urine analysis, pooled human liver microsome (pHLM) assays were performed and evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS) techniques to generate reference spectra of the in vitro phase I metabolites. The in vivo phase I metabolism was investigated by the analysis of more than 20 authentic human urine specimens and compared to the data received from the pHLM assay. Biotransformation of the 5-fluoropentyl side chain and hydrolysis of the terminal methyl ester bond are main phase I biotransformation steps. Two of the identified main metabolites formed by methyl ester hydrolysis or mono-hydroxylation at the indole ring system were evaluated as suitable urinary biomarkers and discussed regarding the interpretation of analytical findings. Exemplary analysis of one urine sample for 5F-MDMB-PICA phase II metabolites showed that two of the main phase I metabolites are subject to extensive glucuronidation prior to renal excretion. Therefore, conjugate cleavage is reasonable for enhancing sensitivity. Commercially available immunochemical pre-tests for urine proved to be unsuitable for the detection of 5F-MDMB-PICA consumption. Copyright (c) 2017 John Wiley & Sons, Ltd.