Abstract The expanding use of emerging synthetic drugs is creating a growing problem for both seized drug analysts and toxicologists because the clandestine suppliers continually tweak the chemical structures to keep one step ahead of the law. Synthetic cathinones, commonly referred to as bath salts, are a specific class of emerging synthetic drugs. These substances are derivatives of cathinone, which is the psychoactive component of the Catha edulis plant, commonly referred to as khat. Of the synthetic cathinone class of compounds, the α-pyrrolidinophenone synthetic cathinone derivatives stand out as one of the most abused designer drugs. The fragmentation behavior of a series of α-pyrrolidinophenone synthetic cathinones was studied with three different ionization and fragmentation techniques to enhance the current understanding of α-pyrrolidinophenone synthetic cathinones in mass spectrometers. Gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) fragmentation is commonly used by seized drug analysts, whereas liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is more commonly used in toxicological analyses. Direct analysis in real time mass spectrometry (DART-MS) is becoming more popular as a screening technique, especially in national laboratories. Each ionization and activation method encourage particular pathways of fragmentation, and whereas some pathways are conserved across all platforms, other pathways are unique to a particular instrument. This study combines isotope-labeling, multi-stage mass spectrometry (MSn) and accurate mass measurements with high-resolution mass spectrometry (HRMS) to enhance the current understanding about α-pyrrolidinophenone synthetic cathinones. This manuscript provides characteristic protonated tandem mass spectrometry fragmentation pathways and the mechanistic origins of the EI-MS fragmentation observed for this class of synthetic cathinones and provides examples of how this knowledge can be applied to the identification of novel synthetic cathinones.

中文翻译：

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α-吡咯烷苯酮合成卡西酮的断裂途径及其在新兴合成卡西酮衍生物鉴定中的应用

摘要 新兴合成药物的广泛使用给缉获的药物分析人员和毒理学家带来了日益严重的问题，因为秘密供应商不断调整化学结构以保持领先于法律一步。合成卡西酮，通常称为浴盐，是一类特殊的新兴合成药物。这些物质是卡西酮的衍生物，卡西酮是 Catha edulis 植物（通常称为 khat）的精神活性成分。在合成卡西酮类化合物中，α-吡咯烷苯酮合成卡西酮衍生物是最常被滥用的设计药物之一。使用三种不同的电离和碎裂技术研究了一系列 α-吡咯烷苯酮合成卡西酮的碎裂行为，以增强当前对质谱仪中 α-吡咯烷苯酮合成卡西酮的理解。气相色谱-电子电离-质谱 (GC-EI-MS) 碎裂常被缉获的药物分析人员使用，而液相色谱-电喷雾电离-串联质谱 (LC-ESI-MS/MS) 更常用于毒理学分析. 实时质谱直接分析 (DART-MS) 作为一种筛选技术正变得越来越流行，尤其是在国家实验室中。每种电离和激活方法都会促进特定的碎裂途径，而有些途径在所有平台上都是保守的，其他途径是特定仪器所独有的。本研究将同位素标记、多级质谱 (MSn) 和精确质量测量与高分辨率质谱 (HRMS) 相结合，以增强目前对 α-吡咯烷苯酮合成卡西酮的理解。这份手稿提供了典型的质子化串联质谱碎裂途径和对这类合成卡西酮观察到的 EI-MS 碎裂的机械起源，并提供了如何将这些知识应用于鉴定新型合成卡西酮的例子。