Dehydration-fragmentation mechanism of cathinones and their metabolites in ESI-CID
Dehydration-fragmentation mechanism of cathinones and their metabolites in ESI-CID
复制标题
卡西酮及其代谢物在 ESI-CID 中的脱水断裂机制
DOI：
10.1002/jms.4538
复制
发表时间：
2020
影响因子：
2.3
通讯作者：
Katagi Munehiro
中科院分区：
文献类型：
--
作者：
Matsuta Shuntaro;Shima Noriaki;Kakehashi Hidenao;Ishikawa Akari;Asai Ryutaro;Nitta Atsushi;Wada Misato;Nakano Shihoko;Kamata Hiroe;Nishiyama Yoshio;Nagatani Hirohisa;Imura Hisanori;Katagi Munehiro
最近，药物市场上出现了各种卡西酮衍生的设计药物（CAT）。本研究检查了电喷雾电离碰撞诱导解离（ESI-CID）过程中CAT脱水离子的生成机制。脱水离子的产生机制取决于卡西酮骨架中的胺分类，其用于鉴定CAT。测定了卡西酮（伯胺）和甲卡西酮（仲胺）脱水过程中脱去的两个氢原子，并通过氘标记实验阐明了反应机理。在两种测试化合物中，与胺氮键合的氢原子被ESI期间添加的质子消除。这提供了具有叔胺结构的CAT（如二甲基卡西酮和α-吡咯烷酮[α-PP]）不发生脱水的证据。然而，研究表明，CAT的两种主要叔胺代谢物（1-OH和2″-氧代）在ESI-CID中产生脱水离子。对α-吡咯烷基丁苯酮（α-PBP）代谢产物的脱水机理进行了研究。稳定同位素标记显示，1-OH代谢物脱水遵循一种简单的机制，其中羟基基团与ESI期间添加的质子一起消除。相比之下，2“-氧代代谢产物的脱水机制涉及三个或更多位置的氢原子沿着羰基氧，表明脱水通过多种机制发生，可能包括氢原子的重排反应。本文中呈现的这些结果表明，ESI-CID中的脱水离子可用于CAT的结构鉴定。
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.