Miller Samuel A, Forero Andrew R, Tose Lilian Valadares, Krechmer Jordan E, Muntean Felician, Fernandez-Lima Francisco
Department of Chemistry and Biochemistry, Florida International University, Miami, FL, 33199, United States.
Bruker Daltonics Inc., Billerica, MA, 01821, United States.
Talanta. 2025 Feb 1;283:127191. doi: 10.1016/j.talanta.2024.127191. Epub 2024 Nov 12.
This study presents an analytical approach coupling novel ambient ionization sources with trapped ion mobility spectrometry (TIMS) and tandem mass spectrometry (MS/MS) for the rapid characterization of fentanyl analogs. Two ambient ionization sources were illustrated for minimal sample preparation and rapid analysis: electrospray ionization (nESI) and direct analysis in real time (DART). Fentanyl analogs can be separated using nESI-TIMS-MS/MS based on differences in their mobility and/or fragmentation pattern; reference mobility spectra are reported for 234 single standards. In contrast, DART-TIMS-MS/MS allowed for the characterization of 201 compounds due to differences in the protonation pattern and efficiency when compared to nESI. The TIMS high resolving power (R > 80) allowed baseline separation for most isomers and mobility trends were established for methylated and fluorinated isomers, with the more compact ortho-substituted analogs showing distinct separation from para- and meta-substituted species. This multi-dimensional strategy offers a comprehensive characterization of fentanyl analogs and other synthetic opioids with minimal sample preparation. This analysis shows significant potential for high-throughput screening (<5 min) and high sensitivity detection (<pg level) of emerging illicit drugs, supporting ongoing forensic investigations and public health initiatives. The use of alternative mobility calibration methods using internal/external standards with ambient ionization sources coupled to TIMS-MS is also provided, enhancing its robustness and applicability.
本研究提出了一种将新型常压电离源与阱式离子淌度质谱（TIMS）和串联质谱（MS/MS）相结合的分析方法，用于快速表征芬太尼类似物。展示了两种用于最小化样品制备和快速分析的常压电离源：电喷雾电离（nESI）和实时直接分析（DART）。基于其淌度和/或碎裂模式的差异，芬太尼类似物可通过nESI-TIMS-MS/MS进行分离；报告了234种单一标准品的参考淌度谱。相比之下，由于与nESI相比质子化模式和效率存在差异，DART-TIMS-MS/MS能够表征201种化合物。TIMS的高分辨能力（R>80）使大多数异构体实现基线分离，并确定了甲基化和氟化异构体的淌度趋势，结构更紧凑的邻位取代类似物与对位和间位取代物种表现出明显的分离。这种多维策略能够在最小化样品制备的情况下对芬太尼类似物和其他合成阿片类药物进行全面表征。该分析在新兴非法药物的高通量筛选（<5分钟）和高灵敏度检测（<皮克水平）方面显示出巨大潜力，为正在进行的法医调查和公共卫生举措提供了支持。还提供了使用内/外标与常压电离源耦合TIMS-MS的替代淌度校准方法，提高了其稳健性和适用性。
