Advancing New Psychoactive Substance Detection by Performance Comparison of High-Resolution Mass Spectrometry Techniques

The rapid proliferation of New Psychoactive Substances (NPS) poses a formidable challenge to public health and law enforcement agencies globally. These substances, designed to mimic controlled drugs while evading legal constraints, present grave risks to users due to their often-unknown composition and pharmacological properties. The surge in NPS is fueled by factors such as low cost, online marketing, and regulatory loopholes. A critical hurdle in combating NPS proliferation is the vast array of derivatives and analogs, including isomers, which can have distinct physiological effects despite structural similarities. Forensic scientists and toxicologists face challenges in detecting, screening, and confirming these substances due to the lack of relevant data and reference standards.

Targeted Screening using High-Resolution Mass Spectrometry (HRMS) represents a pivotal strategy in combating the spread of NPS, offering detection of compounds predefined in target list. Leveraging its resolving power and sensitivity, HRMS facilitates the comprehensive analysis of NPS across various chemical classes and sample types. Moreover, HRMS methods offer flexibility to adapt to evolving NPS trends and emerging threats, enhancing the ability to accurately assess prevalence and distribution.

This study aims to advance HRMS technology for NPS detection by systematically evaluating and comparing three prominent platforms: Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry (LC-QTOF-MS), Liquid Chromatography-Quadrupole-Orbitrap-Mass Spectrometry (LC-Q-Orbitrap-MS), and Trapped Ion Mobility Spectrometry-Time of Flight-Mass Spectrometry (TIMS-TOF-MS). We will assess parameters such as sensitivity, selectivity, and throughput, identifying the most suitable platform for NPS detection in diverse sample matrices. Additionally, we will investigate the isomeric differentiation capabilities of LC-QTOF-MS and TIMS-TOF-MS, focusing on their ability to discern structurally similar NPS isomers. By achieving these objectives, our research aims to enhance the accuracy, efficiency, and reliability of NPS detection methods using HRMS techniques, contributing to more effective strategies for combating the illicit trade and misuse of psychoactive substances. This comparative study platform represents a novel approach that has not been published before, addressing critical gaps in NPS detection, and advancing forensic analytical capabilities. CA/NCF