Elucidating the Gas-Phase Behavior of Nitazene Analog Protomers Using Structures for Lossless Ion Manipulations Ion...

Area of Science:

• Forensic Toxicology
• Analytical Chemistry
• Mass Spectrometry

Background:

• Nitazenes are potent novel synthetic opioids (NSOs) increasingly found in drug overdose cases.
• Their high potency and lack of routine testing lead to under-reporting.
• Current identification methods often require reference standards, delaying analysis.

Purpose of the Study:

• To present the first ion mobility spectrometry (IMS) and collision cross section (CCS) measurements for fourteen nitazene analogs.
• To explore the potential of IMS for reference-free identification of nitazenes in toxicology.
• To investigate the gas-phase behavior of nitazenes using IMS, solvent, and fragmentation studies.

Main Methods:

• Utilized structures for lossless ion manipulations (SLIM)-orbitrap mass spectrometry for IMS and CCS measurements.
• Investigated the effect of water in electrospray ionization (ESI) solutions on IMS distributions.
• Performed IMS-MS/MS experiments to analyze fragmentation patterns and gas-phase protomers.
• Employed cyclic IMS to resolve structurally similar nitazene isomers.

Main Results:

• All fourteen nitazenes showed two distinct IMS distributions.
• Water addition to ESI solutions altered IMS distribution intensities, particularly for nitazenes lacking a nitro group.
• IMS-MS/MS revealed differences in fragmentation patterns between high and low mobility distributions, suggesting three gas-phase protomers.
• Partial resolution of nitazene isomers was achieved using cyclic IMS.

Conclusions:

• IMS provides a powerful tool for the rapid, reference-free identification of emerging nitazenes and other NSOs.
• Understanding nitazene gas-phase behavior through IMS aids in their structural elucidation.
• High-resolution IMS separations integrated with MS workflows can significantly enhance NSO detection rates in forensic laboratories.