The targeted analysis of New Psychoactive Substances in oral fluid through chromatographic-spectrometric methods: review of recent findings

Objective: The oral fluid was demonstrated as an effective matrix to assess drug consumption in forensic settings. Recently, the increasing number of intoxications related to New Psychoactive Substances raised the attention of the scientific community. To this concern, different analytical methods to detect and quantify NPS in oral fluids were developed and validated, most of them based on hyphenated techniques. Materials and methods: A broad-ranging search was conducted on multidisciplinary research databases using "New Psychoactive Substances", "oral fluid", "toxicological analysis", "analytical method", "targeted method", "HPLC-MS/MS", "GC-MS", "GC-MS/MS" alone or in combination as search strings. All research articles published between 2017 and 2021 were considered. Results: Different chromatographic-spectrometric methods to detect and quantify the NPS in oral fluid were reported in the literature. The classes of NPS explored were synthetic cannabinoids, synthetic cathinones, new designer benzodiazepines, synthetic opioids, fentanyl analogues, tryptamines, and phenethylamines. The most used technique was HPLC-MS/MS due to the sensitivity and high throughput. The GC-MS technique was preferred for synthetic cannabinoids, anyway different HPLC-MS/MS methods were developed. Moreover, the LC-HRMS technique was applied for the development of an analytical assay to detect new synthetic opioids and fentanyl analogues. Conclusions: The analytical interest on oral fluid as an effective matrix to assess drug exposure is increasing. The hyphenated techniques were demonstrated effective in the detection of NPS in oral fluids. The most suitable techniques are HPLC-MS/MS due to the sensitivity and the possibility to include different classes of substances in a single analytical run.