Application of mass spectrometry fragmentation patterns for rapid screening and structure identification of fentanyl analogues in suspicious powder

Abstract

Fentanyl analogues are one of the most abused categories of synthetic opioids due to their higher potency in contrast to traditional opioids. Given that fentanyl analogues are obtained by modifying the structure of fentanyl, the evolutionary rules and common fragmentation patterns of fentanyl analogues could be used for rapid screening and structural identification of these substances. Hence, the evolutionary rules and common EI-MS and ESI-MSn fragmentation patterns of fentanyl analogues are summarized based on previous literature in this study. The cleavage of the N-C4 bond is the main fragmentation pathway of fentanyl analogues in ESI-MSn mode, while the side chain cleavage at the N1 position and piperidine ring-breaking rearrangement are the featured fragmentation pathways of fentanyl analogues in EI-MS mode. ESI-MS/MS fragmentation patterns could be applied to identify the Core A (piperidine ring) and Part D (2-(thiophen-2-yl)ethyl, 2-(fluoro-2-phenyl)ethyl and benzyl, etc) of fentanyl analogues and EI-MS fragmentation patterns could be used to characterize Parts B (isobutyryl, valeryl, furan-2-formyl and benzoyl, etc) and C (substituted or unsubstituted monocyclic aromatic groups). Based on the evolutionary rules and fragmentation patterns of fentanyl analogues, five unknown fentanyl analogues in two suspected seizures are identified by LC-Q-Orbitrap/MS and GC-EI-MS. Structures of five unknown fentanyl analogues in suspicious seizures are investigated. Besides, computational results show that EI-MS fragmentation pathways are controlled by both energy barrier and spin-density difference population. Hence, more fragmentation routes are available. This method is intended to provide data for high-speed screening and structural identification of fentanyl analogues for forensic identification and regulation.