Trapped ion mobility mass spectrometry of new psychoactive substances: Isomer-specific identification of ring-substituted cathinones

New psychoactive substances (NPS) are synthetic derivatives of illicit drugs designed to mimic their psychoactive effects. NPS are typically not controlled under drug acts or their legal status depends on their molecular struc-ture. Discriminating isomeric forms of NPS is therefore crucial for forensic laboratories. In this study, a trapped ion mobility spectrometry time-of-flight mass spectrometry (TIMS-TOFMS) approach was developed for the identification of ring-positional isomers of synthetic cathinones, a class of compounds representing two-third of all NPS seized in Europe in 2020. The optimized workflow features narrow ion-trapping regions, mobility calibration by internal reference, and a dedicated data-analysis tool, allowing for accurate relative ion-mobility assessment and high-confidence isomer identification. Ortho-, meta-and para-isomers of methylmethcathinone (MMC) and bicyclic ring isomers of methylone were assigned based on their specific ion mobilities within 5 min, including sample preparation and data analysis. The resolution of two distinct protomers per cathinone isomer added to the confidence in identification. The developed approach was successfully applied to the unambiguous assignment of MMC isomers in confiscated street samples. These findings demonstrate the potential of TIMS-TOFMS for forensic case work requiring fast and highly-confident assignment cathinone-drug isomers in confiscated samples.

Automated summary

A method using trapped ion mobility spectrometry and time-of-flight mass spectrometry was developed to identify different ring-positional isomers in synthetic cathinones. The method allows for accurate ion mobility assessment and high-confidence isomer identification through narrow ion-trapping regions, internal reference mobility calibration, and a dedicated data analysis tool. The method was successfully applied to the unambiguous assignment of isomers in confiscated street samples.