Department of Chemistry, Clemson University, Clemson, South Carolina 29634, United States.
J Am Soc Mass Spectrom. 2024 Mar 6;35(3):582-589. doi: 10.1021/jasms.3c00419. Epub 2024 Feb 15.
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 Å, 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 /. 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.
合成大麻素是新型精神活性物质（NPS）的一个子类，是实验室制造的物质，其化学结构与大麻植物中天然存在的物质相似。这些物质中有许多是非法制造的，与严重的健康问题有关，因此需要开发能够对已知和以前未检测到的化合物进行特征描述的分析方法。本工作专注于一种新的结构无损离子操纵（SLIM）IM-MS 方法，用于区分和结构表征合成大麻素代谢物，特别是 MDA-19/BUTINACA、JWH-018 和 JWH-250 异构体组。这些不同的化合物类别在结构上非常相似，仅在一个或几个官能团的位置上有所不同；这导致了测量的碰撞截面（CCS）值的相似性。然而，SLIM IM 的高分辨率提供了对许多这些异构体的充分分离，例如，JWH-250 代谢物 N-4-OH、N-5-OH 和 5-OH 的加钠离子，它们的 CCS 值分别为 187.5、182.5 和 202.3 Å。在由于几乎相同的 CCS 而无法进行基线分离的具有挑战性的情况下，例如对于 JWH-018 异构体，丹磺酰氯的简单衍生化选择性地与 6-OH 化合物反应，从而使用 CCS 和 / 的组合来区分所有异构体。最后，通过使用 SLIM IM 迁移对齐 MS/MS 碎片化来证明了该方法用于未知物结构阐明的机会。不同的 MDA-19/BUTINACA 异构体首先进行迁移分离，然后可以单独激活，从而为靶向识别和结构确定提供独特的片段。总的来说，所描述的 SLIM IM-MS/MS 工作流程具有很大的潜力，可作为一种快速筛选工具，用于表征新兴的 NPS，如合成大麻素及其代谢物。
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