Screening strategy for ketamine-based new psychoactive substances using fragmentation characteristics from high resolution mass spectrometry

Recreational designer drugs called new psychoactive substances (NPS) are emerging and pose enormous risks to public health. Detection of recently discovered or unreported NPS remains a huge challenge by using traditional targeted mass spectrometry methods. Here a novel screening strategy was developed to detect both known and novel analogs of NPS based on fragmentation characteristics from liquid chromatography-high resolution mass spectrometry (LC-HRMS). The HRMS fragmentation pathway of one selected NPS family was investigated to form a database containing predicted drugs as well as their mass characteristics. During the study, an unexpected substituent effect was found to distinguish geometric isomers. Seventy-eight seized samples were analyzed using this strategy, four ketamine-based NPS were detected and three of them were newly marketed. The substituent effect predicted the position of their phenylic substituent, the results were confirmed by NMR.