Systematic analysis of novel psychoactive substances. I. Development of a compound database and HRMS spectral library

Abstract

With the rise in illicit use of novel psychoactive substances (NPS), there is a need to comprehensively screen for drugs in this class. In the present project to explore the screening potential of high resolution mass spectrometry (HRMS) for NPS, liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) was utilized to generate a tandem mass spectrometry (MS/MS) spectral library in positive electrospray ionization mode. The library contains data for 252 NPS from multiple classes, including cathinones, piperazines, tryptamines, and synthetic cannabinoids. Spectra were collected by flow injection analysis under standardized conditions at three different collision energies (10, 20, and 40 eV) for each compound. In addition to the spectral library, a compound database was created to further enhance the screening potential of the LC-QTOF-MS. This database contains chemical and structural information for 875 NPS compounds and metabolites that can be used to help aid the identification of unknowns in a full mass scan. To demonstrate the applicability of the HRMS library, 13 serum samples were spiked with NPS from various structural classes with up to five different NPS per sample, and four authentic seized drug case samples, were analyzed. The HRMS library search successfully identified 32 of the 35 compounds present in the spiked serum samples. In addition, HRMS-based screening of seized samples provided results consistent with the official forensic laboratory findings. The combination of a HRMS spectral library, compound database, and accurate mass LC-QTOF-MS analysis represents a useful tool for the identification of NPS in forensic screening applications.