Various cathinone‐derived designer drugs (CATs) have recently appeared on the drug market. This study examined the mechanism for the generation of dehydrated ions for CATs during electrospray ionization collision‐induced dissociation (ESI‐CID). The generation mechanism of dehydrated ions is dependent on the amine classification in the cathinone skeleton, which is used in the identification of CATs. The two hydrogen atoms eliminated during the dehydration of cathinone (primary amine) and methcathinone (secondary amine) were determined, and the reaction mechanism was elucidated through the deuterium labeling experiments. The hydrogen atom bonded to the amine nitrogen was eliminated with the proton added during ESI, in both of the tested compounds. This provided evidence that CATs with tertiary amine structures (such as dimethylcathinone and α‐pyrrolidinophenones [α‐PPs]) do not undergo dehydration. However, it was shown that the two major tertiary amine metabolites (1‐OH and 2″‐oxo) of CATs generate dehydrated ions in ESI‐CID. The dehydration mechanisms of the metabolites of α‐pyrrolidinobutiophenone (α‐PBP) belongs to α‐PPs were also investigated. Stable‐isotope labeling showed the dehydration of the 1‐OH metabolite following a simple mechanism where the hydroxy group was eliminated together with the proton added during ESI. In contrast, the dehydration mechanism of the 2″‐oxo metabolite involved hydrogen atoms in three or more locations along with the carbonyl group oxygen, indicating that dehydration occurred via multiple mechanisms likely including the rearrangement reaction of hydrogen atoms. These findings presented herein indicate that the dehydrated ions in ESI‐CID can be used for the structural identification of CATs.

中文翻译：

---

卡西酮及其代谢产物在ESI-CID中的脱水-碎片化机理

最近，在药物市场上出现了多种由卡西酮衍生的名牌药物（CAT）。这项研究检查了电喷雾电离碰撞诱导解离（ESI-CID）期间CAT脱水离子生成的机理。脱水离子的生成机理取决于在Cathinone骨架中的胺分类，该分类用于CAT的识别。确定了在卡西酮（伯胺）和甲基卡西酮（仲胺）脱水过程中消除的两个氢原子，并通过氘标记实验阐明了反应机理。在两种测试化合物中，在ESI期间通过添加质子消除了与胺氮键合的氢原子。这提供了具有叔胺结构的CAT（例如二甲基卡西酮和α-吡咯烷基苯酮[α-PPs]）不会脱水的证据。但是，结果表明，CAT的两种主要的叔胺代谢物（1-OH和2″ -oxo）在ESI-CID中产生脱水离子。还研究了α-吡咯烷基丁苯酮（α-PBP）属于α-PPs代谢产物的脱水机理。稳定同位素标记显示1-OH代谢物的脱水遵循简单的机制，其中在ESI过程中消除了羟基以及添加的质子。相比之下，2”-氧代代谢产物的脱水机理涉及三个或更多位置的氢原子以及羰基氧，表明脱水可能通过多种机制发生，包括氢原子的重排反应。本文介绍的这些发现表明ESI-CID中的脱水离子可用于CAT的结构鉴定。