Investigation of Fragmentation Pathways of Fentanyl Analogues and Novel Synthetic Opioids by Electron Ionization High-Resolution Mass Spectrometry and Electrospray Ionization High-Resolution Tandem Mass Spectrometry

The global drug market is characterized by the fast development of new psychoactive substances such as fentanyl analogues and novel synthetic opioids, the detection of which is complicated by the lack of appropriate quality control procedures and references. Herein, we analyze the fragmentation pathways and characteristic ions of 25 novel fentanyl analogues and 5 novel synthetic opioids by electron ionization (EI) and electrospray ionization (ESI) high-resolution mass spectrometry to provide a reference for the identification of these species. In the ESI mode, fentanyl analogues mainly undergo piperidine ring degradation, phenethyl and piperidine ring dissociation, and piperidine ring and amide moiety cleavage, while piperidine ring degradation and phenethyl and piperidine ring dissociation are the major pathways in the EI mode. The five novel synthetic opioids largely undergo amide group dissociation and N-cyclohexyl bond cleavage in the ESI mode. Thus, this work facilitates the detection and quantitation of fentanyl analogues and novel synthetic opioids or other substances with similar structures in forensic laboratories.