Dielectric Barrier Discharge Ionization (DBDI) Enables Rapid Analysis of New Psychoactive Substances with Ion Mobility-Mass Spectrometry

Abstract

New psychoactive substances (NPS) present a major public health crisis across the world due to their variable potency, constant evolution within the recreational drug community, and ability to skirt legal/policy regulations. Because of the frequency with which new substances are introduced, it is increasingly difficult for clinical, toxicological, and forensic laboratories to keep up with the newest drug threats, presenting a critical need for development of rapid analytical methods capable of confident structural characterization. In the present work, we demonstrate successful coupling of a commercial dielectric barrier discharge ionization (DBDI) source to two ion mobility-mass spectrometry (IM-MS) instruments, including high-resolution Structures for Lossless Ion Manipulations (SLIM). The DBDI source enables rapid introduction of NPS which can subsequently be characterized by IM-MS. Specifically, we show that IM can be used to differentiate structural isomers of synthetic cannabinoids, benzodiazepines, nitazenes, and fentanyl analogues with very minor differences in their collision cross sections (CCS). We also note that the mobility spectra for those compounds presenting protonation site isomers (“protomers”) differed from previous work on electrospray ionization (ESI)-generated species from our group and others; this observation is not unsurprising given the different fundamental mechanism of DBD ionization and warrants future interrogation. Finally, we demonstrate the combination of ion mobility with tandem mass spectrometry (MS/MS) for mobility-aligned fragmentation that provided additional structural information for confident characterization. The coupling of DBDI with IM-MS/MS (especially high-resolution IM) constitutes a powerful approach for rapid analysis of several classes of NPS that could be used to improve throughput in the future.