Automated rapid screening of new psychoactive substances using benchtop NMR technology combined with database search

To combat the prevalence of new psychoactive substances (NPS), there is need for routine and efficient screening of the substantial amount of seized NPS samples. In this study, a rapid NPS screening method was established using benchtop NMR in combination with spectrum database search toolkit integrated within the MestReNova software. A benchtop ¹H NMR spectral database comprising 360 NPS reference materials was constructed for search purposes. While NPS analogues with minimal structural differences (for instances in one methyl, ethyl, oxygen, or halogen atom) exhibited high spectral similarity, they remained differentiable using benchtop NMR. Chemical shift correction, along with identification and removal of solvent peaks were key factors influencing the accuracy of the search results. The performance of four database search algorithms was compared using the spectra of 50 seized NPS samples. Peak purity search algorithm exhibited the highest positive detection rate. All 40 single component samples were correctly identified with the first hit. Additionally, novel unknown compounds were retrieved along with their structural analogues, helping in structure prediction and elucidation. Although peak purity search algorithm was not fully effective in identifying all analytes in the mixture sample, it successfully detected the major component. The established NPS screening method, integrating benchtop NMR with database search is rapid, efficient, and user-friendly, providing more straightforward structure information. With the increasing availability of commercial database search toolkit, benchtop NMR is expected to be widely applied for the rapid screening of NPS and illicit drugs in the near future.