关键词: 2-benzyl benzimidazole 96-well format LC-MS/MS New psychoactive substances electromembrane extraction forensic analysis liquid-phase microextraction nitazenes synthetic opioids whole blood

Mesh : Tandem Mass Spectrometry / methods Analgesics, Opioid Chromatography, High Pressure Liquid / methods Illicit Drugs / analysis Benzimidazoles

来  源:   DOI:10.1093/jat/bkad071   PDF(Pubmed)

Abstract:
Benzimidazole opioids, often referred to as nitazenes, represent a subgroup of new psychoactive substances with a recent increase in fatal overdoses in the USA and Europe. With a variety of analogs emerging on the illicit drug market, forensic laboratories are challenged to identify these potent drugs. We here present a simple quantitative approach for the determination of nine nitazene analogs, namely, clonitazene, etodesnitazene, etonitazene, etonitazepyne, flunitazene, isotonitazene, metodesnitazene, metonitazene and protonitazene in whole blood using liquid-phase microextraction and electromembrane extraction in a 96-well format and liquid chromatography-tandem mass spectrometry. Green and efficient sample preparation was accomplished by liquid-phase microextraction in a 96-well format and resulted in high extraction yields for all analytes (>81%). Here, blood diluted with buffer (1:1, %v) was extracted from a donor compartment across a thin organic liquid membrane and into an aqueous acceptor solution. The acceptor solution was collected and directly injected into the analysis platform. Chromatographic separation was accomplished with a biphenyl column, allowing for a baseline separation of the structural isomers isotonitazene and protonitazene before detection by multiple reaction monitoring. Validation was performed according to Scientific Working Group of Forensic Toxicology guidelines. The calibration range was from 0.5 to 50 nM (except for protonitazene and clonitazene from 0.1 nM) with good linearity and limits of detection down to 0.01 nM. An AGREEprep assessment was performed to evaluate sample preparation greenness, with a final score of 0.71. Nitazenes represent a current threat to public health, and analytical methods that cover a wide range of these analogs are limited. Here, the described method may assist in the detection of nitazenes in whole blood and prevent these substances from being missed in postmortem investigations.
摘要:
苯并咪唑类阿片,通常被称为硝基苯,代表一个新的精神活性物质亚组,最近在美国和欧洲的致命过量剂量有所增加。随着非法药物市场上各种类似物的出现,法医实验室面临着识别这些强效药物的挑战。我们在这里提出了一种简单的定量方法来测定九种硝基苯类似物,即,氯硝唑,etotesnitazene,依托氮嗪,依托硝氮肽,氟尼氮烯,异硝基苯,美托硝基苯,甲硝唑,使用96孔格式的液相微萃取和电膜萃取以及液相色谱串联质谱法在全血中的质子氮烯。绿色和有效的样品制备是通过96孔格式的液相微提取完成的,并导致所有分析物的高提取率(>81%)。这里,将用缓冲液(1:1,%v)稀释的血液从供体隔室中通过薄的有机液膜提取并进入水性受体溶液。收集受体溶液并直接注入分析平台。用联苯柱完成色谱分离,允许在通过多反应监测进行检测之前,对结构异构体异单氮唑和单氮唑进行基线分离。根据法医毒理学科学工作组指南进行验证。校准范围为0.5至50nM(除了0.1nM的质子氮嗪和氯硝唑),具有良好的线性和低至0.01nM的检测限。进行AGREEPrep评估以评估样品制备的绿色度,最终得分为0.71。硝胺烯是当前对公众健康的威胁,和分析方法,涵盖广泛的这些类似物是有限的。这里描述的方法可以帮助检测全血中的硝基苯并防止这些物质在验尸调查中被遗漏。
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