Benefits of derivatization in GC-MS-based identification of new psychoactive substances

Drug isomer identification is a significant problem in forensic laboratories due to the rise of New Psychoactive Substances (NPS). Correct identification of the precise isomeric form is of crucial importance as legal controls can vary among individual isomers. Currently, GC-MS is the method of choice in routine drug identification. This technique, however, falls short for isomeric differentiations due to i) very similar chromatographic behavior, ii) almost identical mass spectra, and iii) limited availability of reference standards. Unambiguous NPS identification often requires additional analysis on advanced analytical instrumentation unavailable in small-scale routine laboratories. This work demonstrates the advantages of an easy and robust derivatization step for GC-MS-based NPS identification. Derivatized extracts yield shelf lives of multiple years, eliminating the need to frequently re-prepare reference standards. After derivatization, chromatographic selectivity and peak shapes are improved enabling identification on retention time. For fluoroamphetamine ring-isomers the mass spectra of their derivates differ more significantly allowing robust assignment through a simple ion abundance-ratio check. Mass spectra of the derivatized mephedrone ring-isomers were visually still very similar. However, isomers could be identified by using Linear Discriminant Analysis (LDA). In a retrospective analysis of 132 mass spectra recorded between 2015 and 2020, a 100% correct classification was achieved using external training data from 2020. Finally, derivatization aids structural elucidation of NPS by the inability to form derivates for tertiary amine isomers as shown for a dimethylated cathinone. This study shows that in specific cases NPS can robustly be identified using conventional GC-MS instrumentation in combination with active ingredient derivatization.