Department of Forensic and Investigative Science, West Virginia University, Morgantown, WV, USA.
C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA.
Drug Test Anal. 2020 Jul;12(7):957-967. doi: 10.1002/dta.2794. Epub 2020 Apr 13.
Fentanyl is a synthetic opioid that has been approved by the FDA as a general anesthetic because of its rapid onset and high potency. However, since 2013 an opioid epidemic involving fentanyl or fentanyl-related compounds (FRCs) has swept the United States and caused numerous deaths in every state. The identification of novel FRCs is complicated by the rapid turnover of modifications to the core fentanyl structure. In this study, a series of 16 FRCs were analyzed using electrospray ionization tandem mass spectrometry (ESI-MS/MS) to gain a deeper understanding of the conserved and unique fragmentation behaviors associated with substitution to the core fentanyl structure. This work provides an approach, based on the product ions from ESI-MS/MS, to identify the modification site(s) on the core fentanyl structure for FRCs. Five common locations of substitution to the core fentanyl structure were used to assess the effect of substitution on the fragmentation behavior of FRCs. The proposed fragmentation pathways are supported through the combination of isotopic labeling, multi-stage mass spectrometry (MS ), and accurate mass measurements with high-resolution mass spectrometry (HRMS). The identification of primary product ions specific to regions of substitution provides an additional tool for the identification of the location of substitution to the core fentanyl structure, which ultimately will assist toxicologists and seized drug analysts in the identification of emerging FRCs.
芬太尼是一种合成阿片类药物，由于其起效迅速和效力高，已被 FDA 批准作为全身麻醉剂。然而，自 2013 年以来，涉及芬太尼或芬太尼相关化合物（FRC）的阿片类药物泛滥席卷美国，导致每个州都有大量死亡。由于核心芬太尼结构的修饰变化迅速，新型 FRC 的鉴定变得复杂。在这项研究中，使用电喷雾电离串联质谱（ESI-MS/MS）分析了一系列 16 种 FRC，以更深入地了解与核心芬太尼结构取代相关的保守和独特的碎裂行为。这项工作提供了一种基于 ESI-MS/MS 的产物离子来识别 FRC 核心芬太尼结构上修饰位置的方法。使用核心芬太尼结构的五个常见取代位置来评估取代对 FRC 碎裂行为的影响。所提出的碎裂途径通过同位素标记、多级质谱（MS）和高分辨率质谱（HRMS）的精确质量测量得到支持。鉴定特定取代区域的主要产物离子为鉴定核心芬太尼结构的取代位置提供了另一种工具，这最终将有助于毒理学家和缴获药物分析师识别新兴的 FRC。
