Identification of 3-chlorophenmetrazine (3-CPM) from new psychoactive substances products and analytical differentiation from the ortho- and para-substituted isomers.

内容摘要

3-Chlorophenmetrazine (3-CPM) is a phenmetrazine analog that has been detected in new psychoactive substance (NPS) products sold on the market. The objective of this study was to perform an analytical characterization of 3-CPM identified in NPS products. In addition, 2-chlorophenmetrazine (2-CPM) and 4-chlorophenmetrazine (4-CPM), which are positional isomers of 3-CPM, were synthesized, and analytical methods for their differentiation were validated to prevent misidentification of the three CPM isomers. Samples were analyzed using liquid chromatography with photodiode array detection (LC/PDA), liquid chromatography-high resolution mass spectrometry (LC/HRMS), gas chromatography-mass spectrometry (GC/MS), gas chromatography-high resolution mass spectrometry (GC/HRMS), nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography. Four NPS products sold between October 2022 and February 2023 were found to mainly contain trans-3-CPM, as determined by NMR analysis. Quantitative analysis showed that the powder and crystal products contained approximately 0.86-1.98 g of 3-CPM per package, whereas the tablet product contained approximately 0.10 g of 3-CPM per tablet. In chromatographic analyses, 2-CPM, 3-CPM, and 4-CPM were distinguishable based on retention times using octadecylsilyl silica gel (ODS) and phenyl columns for LC/PDA, and HP-5ms and CycloSil-B columns for GC/MS. Small differences were observed between UV spectra of 2-CPM/3-CPM and that of 4-CPM. Furthermore, 2-CPM produced a characteristic product ion in the LC/HRMS spectrum. The three positional isomers (2-, 3-, and 4-CPM) can be differentiated using LC and GC-based analytical methods. The analytical data presented in this study will facilitate the structural elucidation and accurate identification of novel phenmetrazine analogs in future investigations.