Qualitative and Quantitative Analysis of New Psychoactive Substances and Related Metabolites Using Liquid Chromatography-Ion Mobility-Mass Spectrometry (LC-IM-MS)

The increasing prevalence of novel psychoactive substances (NPS) in illicit drug markets has posed significant challenges for forensic and clinical toxicology, primarily due to the structural similarity and diversity among these compounds. This dissertation investigates the application of advanced liquid chromatography-ion mobility-mass spectrometry (LC-IM-MS/MS) techniques, using the high-resolution Structures for Lossless Ion Manipulations (SLIM) platform and the drift tube ion mobility spectrometry (DT-IMS), for the qualitative and quantitative analysis of various types of synthetic opioids, synthetic cannabinoids, psychedelics and xylazine. By combining IMS separations with mass spectrometry and targeted chemical derivatization, this work enhances the ability to distinguish and characterize structural isomers and metabolites, overcoming limitations in conventional analytical methods. Key findings include the novel use of metal ion adducts to improve mobility separations of fentanyl isomers, the application of dansyl chloride derivatization for enhanced resolution of cannabinoid and xylazine metabolites and the identification of protonation site isomers in fentanyl analogs and other classes of NPS using mobility-aligned fragmentation and adducts. These methodologies demonstrate high sensitivity, resolving power and reproducibility, with significant benefits for improving NPS characterization workflows in forensic, clinical and pharmaceutical settings. This work contributes to the growing field of multidimensional separations, addressing critical public health needs by providing tools for the rapid and accurate identification of dangerous substances in complex matrices.