A novel screening workflow for nitazene analogs using LC-MS/MS precursor ion scan acquisition

Area of Science:

• Forensic Chemistry
• Analytical Chemistry
• Toxicology

Background:

• Traditional screening methods struggle to keep pace with evolving novel psychoactive substances (NPS).
• High-resolution mass spectrometry (HRMS) offers non-targeted acquisition for broad NPS detection but is costly.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is more accessible to forensic labs.

Purpose of the Study:

• To develop and validate an alternative screening method for nitazene analogs using LC-MS/MS.
• To evaluate the efficacy of precursor ion scan (PIS) acquisition for NPS detection.
• To provide a cost-effective solution for forensic laboratories lacking HRMS.

Main Methods:

• Developed a liquid-liquid extraction method for whole blood samples.
• Employed precursor ion scan (PIS) acquisition on an LC-MS/MS platform.
• Validated the method with a 0.5 ng/mL limit of detection and 1.0 ng/mL administrative cutoff.

Main Results:

• The PIS-LC-MS/MS method successfully identified all nitazenes in proof-of-concept samples with no false positives or negatives.
• The method demonstrated robustness against matrix effects, carryover, and interferences.
• Presumptive identification of emerging nitazene analogs not included in initial method scope was achieved.

Conclusions:

• Precursor ion scan (PIS) acquisition on LC-MS/MS is a viable and cost-effective alternative to HRMS for screening nitazene analogs.
• This method enhances the ability of forensic laboratories to rapidly identify emerging NPS threats.
• A proposed workflow aids in the identification of known and emerging nitazene analogs.