Developments in high-resolution mass spectrometric analyses of new psychoactive substances

Abstract

The proliferation of new psychoactive substances (NPS) has necessitated the development and improvement of current practices for the detection and identification of known NPS and newly emerging derivatives. High-resolution mass spectrometry (HRMS) is quickly becoming the industry standard for these analyses due to its ability to be operated in data-independent acquisition (DIA) modes, allowing for the collection of large amounts of data and enabling retrospective data interrogation as new information becomes available. The increasing popularity of HRMS has also prompted the exploration of new ways to screen for NPS, including broad-spectrum wastewater analysis to identify usage trends in the community and metabolomic-based approaches to examine the effects of drugs of abuse on endogenous compounds. In this paper, the novel applications of HRMS techniques to the analysis of NPS is reviewed. In particular, the development of innovative data analysis and interpretation approaches is discussed, including the application of machine learning and molecular networking to toxicological analyses.

Detecting novel psychoactive substances around the world

“…More recently, broad-spectrum HRMS methods, which features high mass accuracy for untargeted screening analysis, have become of particular interest [13]. In addition, the possible elucidation of the structures of unknown designer drugs [14,15], innovative data analysis, and machine learning techniques for result interpretation [16,17 ▪▪ ] have been developed and can successfully be applied to NPS metabolite investigation [18].…”

Tackling new psychoactive substances through metabolomics: UHPLC-HRMS study on natural and synthetic opioids in male and female murine models

“…The target methods, typically based on low resolution mass spectrometry (LRMS), are not able to reveal NPS, which may present slight modifications respect to known molecules, nor to identify their metabolites; therefore, target methods require frequent database updates to include new substances, followed by subsequent re-validation of analytical methods. In order to mitigate these issues, untargeted high-resolution MS (HRMS) represents an alternative approach for the development of new screening strategies; in fact, untargeted methods, have the potential to not be tied to the chemical structure of the compounds and are then more suitable for NPS analysis 8 . Specific mass spectrometric approaches have been recently identified as valuable strategies for some NPS class detection 9 , 10 , but they generally rely on structure similarity to known molecules.…”

Use of innovative, cross-disciplinary in vitro, in silico and in vivo approaches to characterize the metabolism of chloro-alpha-pyrrolidinovalerophenone (4-Cl-PVP)

“…In order to make the best use of metabolic data obtained in vitro and in vivo, bioinformatics analyses of liquid chromatography-high resolution mass spectrometry (LC-HRMS) data are becoming increasingly valuable (Seidl et al 2022;Klingberg et al 2022). For example, molecular networking facilitates the computational reprocessing of big data and is used increasingly in analytical and clinical toxicology labs (Allard et al 2019(Allard et al , 2020Le Daré et al 2020b).…”