合成大麻素,新精神活性物质(NPS)的一个亚类,是实验室制造的物质,化学上与大麻植物中天然发现的物质相似。其中许多物质是非法制造的,并与严重的健康问题有关,这促使需要开发能够表征已知和以前未检测到的化合物的分析方法。这项工作的重点是一种新型结构的无损离子操纵(SLIM)IM-MS方法的分化和结构表征的合成大麻素代谢物,特别是MDA-19/布丁纳卡,JWH-018和JWH-250异构体基团。这些不同的化合物种类在结构上非常相似,仅在一个或几个功能组的位置上不同;这在测得的碰撞横截面(CCS)值中产生了相似性。然而,SLIMIM的高分辨率提供了许多这些异构体的充分分离,如酸化JWH-250代谢物N-4-OH,N-5-OH,5-OH,显示的CCS分别为187.5、182.5和202.3µ2。在具有挑战性的情况下,由于几乎相同的CCS而排除了基线分离,例如对于JWH-018异构体,通过与6-OH化合物选择性反应的丹磺酰氯的简单衍生化,以使用CCS和m/z的组合来区分所有异构体。最后,通过使用SLIMIM迁移率对齐的MS/MS片段证明了使用该方法对未知物进行结构阐明的机会。首先将不同的MDA-19/BUTINACA异构体迁移率分离,然后可以单独激活,产生独特的片段,用于靶向鉴定和结构确定。总的来说,所描述的SLIMIM-MS/MS工作流程提供了作为表征新出现的NPS如合成大麻素及其代谢物的快速筛选工具的巨大潜力.
Synthetic cannabinoids, a subclass of new psychoactive substances (NPS), are laboratory-made substances that are chemically similar to those found naturally in the cannabis plant. Many of these substances are illicitly manufactured and have been associated with severe health problems, prompting a need to develop analytical methods capable of characterizing both known and previously undetected compounds. This work focuses on a novel Structures for Lossless Ion Manipulations (
SLIM) IM-MS approach to the differentiation and structural characterization of synthetic cannabinoid metabolites, specifically MDA-19/BUTINACA, JWH-018, and JWH-250 isomer groups. These different compound classes are structurally very similar, differing only in the position of one or a few functional groups; this yielded similarity in measured collision cross section (CCS) values. However, the high resolution of
SLIM IM provided adequate separation of many of these isomers, such as sodiated JWH-250 metabolites N-4-OH, N-5-OH, and 5-OH, which displayed CCS of 187.5, 182.5, and 202.3 Å2, respectively. In challenging cases where baseline separation was precluded due to nearly identical CCS, such as for JWH-018 isomers, simple derivatization by dansyl chloride selectively reacted with the 6-OH compound to provide differentiation of all isomers using a combination of CCS and m/z. Finally, the opportunity to use this method for structural elucidation of unknowns was demonstrated by using
SLIM IM mobility-aligned MS/MS fragmentation. Different MDA-19/BUTINACA isomers were first mobility separated and could then be individually activated, yielding unique fragments for both targeted identification and structural determination. Overall, the described
SLIM IM-MS/MS workflow provides significant potential as a rapid screening tool for the characterization of emerging NPS such as synthetic cannabinoids and their metabolites.