Abstract：
The opioid crisis in the United States is being fueled by the rapid emergence of new fentanyl analogs and precursors that can elude traditional library-based screening methods, which require data from known reference compounds. Since reference compounds are unavailable for new fentanyl analogs, we examined if fentanyls (fentanyl + fentanyl analogs) could be identified in a reference-free manner using a combination of electrospray ionization (ESI), high-resolution ion mobility (IM) spectrometry, high-resolution mass spectrometry (MS), and higher-energy collision-induced dissociation (MS/MS). We analyzed a mixture containing nine fentanyls and W-15 (a structurally similar molecule) and found that the protonated forms of all fentanyls exhibited two baseline-separated IM distributions that produced different MS/MS patterns. Upon fragmentation, both IM distributions of all fentanyls produced two high intensity fragments, resulting from amine site cleavages. The higher mobility distributions of all fentanyls also produced several low intensity fragments, but surprisingly, these same fragments exhibited much greater intensities in the lower mobility distributions. This observation demonstrates that many fragments of fentanyls predominantly originate from one of two different gas-phase structures (suggestive of protomers). Furthermore, increasing the water concentration in the ESI solution increased the intensity of the lower mobility distribution relative to the higher mobility distribution, which further supports that fentanyls exist as two gas-phase protomers. Our observations on the IM and MS/MS properties of fentanyls can be exploited to positively differentiate fentanyls from other compounds without requiring reference libraries and will hopefully assist first responders and law enforcement in combating new and emerging fentanyls.
摘要：
新的芬太尼类似物和前体的迅速出现加剧了美国的阿片类药物危机，这些药物和前体可以避开传统的基于文库的筛查方法，这需要来自已知参考化合物的数据。由于参考化合物无法用于新的芬太尼类似物，我们检查了芬太尼（芬太尼+芬太尼类似物）是否可以使用电喷雾电离（ESI）的组合以无参考的方式鉴定，高分辨率离子迁移(IM)光谱法，高分辨率质谱(MS)，和更高能量的碰撞诱导解离（MS/MS）。我们分析了含有九种芬太尼和W-15(结构相似的分子)的混合物,发现所有芬太尼的质子化形式表现出两种基线分离的IM分布,其产生不同的MS/MS模式。在分裂时，所有芬太尼的IM分布都产生了两个高强度片段，由胺位点切割产生。所有芬太尼的较高迁移率分布也产生了几个低强度的碎片，但令人惊讶的是，这些相同的片段在较低的迁移率分布中表现出更大的强度。该观察表明芬太尼的许多片段主要源自两种不同的气相结构中的一种(提示原聚体)。此外，相对于较高的迁移率分布，增加ESI溶液中的水浓度增加了较低迁移率分布的强度，这进一步支持芬太尼作为两种气相促进剂存在。我们对芬太尼的IM和MS/MS特性的观察结果可用于将芬太尼与其他化合物进行正向区分，而无需参考库，并有望帮助急救人员和执法部门对抗新的和新兴的芬太尼。
