The role of analytical pharmacotoxicology in adressing the main functions of the National Early Warning System on NPS

Abstract

In compliance with the European Council Decision 2005/387/JHA, the Italian AntiDrug Policies Department designated the National Center for Addiction and Doping of the Istituto Superiore di Sanità (ISS) to organize and manage the National Early Warning System (NEWS) on New Psychoactive Substances (NPS) to promote a rapid exchange of information on NPS within Italy and between Italy and the EU. The analytical pharmacotoxicology Unit of the Center supports NEWS with screening and confirmation of NPS presence in conventional and non-conventional biological matrices from acute and fatal intoxication cases. Furthermore, yearly, pure standards of new NPS are tested and provided to Laboratories from collaborative centres and proficiency testing on NPS in oral fluid and hair are organized. Different analytical technologies, including high-sensitivity gas chromatography-mass spectrometry (GC-MS) and tandem mass spectrometry (GC-MS-MS), liquid chromatography-tandem mass spctrometry (LC-MS-MS) and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) are used for a screening and confirmation analysis of classic drugs, prescription medicines and new psychoactive substances in and their metabolites in blood, plasma, urine, hair and oral fluid from intoxication cases and clinical trials. Sample preparation involves both liquid-liquid or solid phase extraction. Dilute and shoot methodology is also applied. During 2021 and first months of 2022, around 80 different psychoactive substances, including new synthetic opioids and/or metabolites were identified in urine from 296 spanish patients with a history of opioid use disorder; 12 classic drugs and NPS were detected in hair from 300 mexican pregnant women; cocaine, THC, heroin, methadone, ketamine and mephedrone and metabolites were determined in urine from 76 italian prisoners; JWH-122 and JWH-210, UR-144 were quantified in oral fluid from consumers and finally some cases of intoxications with fentanyl, norfentanyl and analogs were also disclosed. Furthermore, two exercises of Proficiency testing for NPS in oral fluid and hair were organized. Samples from both matrices were prepared in cooperation with Comedical (Trento, Italy). For the 2021 round classic drugs together with 5-fluoro CUMYL-PeGACLONE, 5-fluoro MDMB-PICA, AB-FUBINACA,5F-ADB, Ethylone, Euthylone, Furanylfentanyl, Ocfentanyl, Isobutyryl fentanyl, Fentanyl and Isotonitazene were included. For the 2022 round, classic drugs plus 5-MMPA, Methoxpropamine, Brorphine, Butonitazene, Etodesnitazene, Flunitazene, 4-fluoro MDMB-BUTICA, 5-fluoro CUMYL—PICA, 5-fluoro EDMB-PICA, 3-Methylmethcathinone, ADB-4en-PINACA, MDMB-4en-PICA were comprises. About 20 different pharmacotoxicological national laboratories participated in the exercised with very variable quali-quantitative results. Although the NPS phenomenon is not uniform, it is well known as a global problem, concerning all the region of the world. Due to the mutating nature of the phenomenon, we believe that investments in toxicological and forensic analytical data sources are strongly needed. Differently from the past when psychotropic drugs occupied the fingers of two hands, in the 21th century, more than 1000 NPS have been identified. Not all of them found the same diffusion in the illicit market, but many of them are temporary adulterant of substitute of controlled compounds or finally fake drugs. The values of accurate and immediately available toxicological and forensic data are crucial to the implementation of national and international early warning system on NPS. Indeed, the drug related severe intoxications and fatalities are seldom associated with the consumption of one substance alone. Drug consumption patterns are often characterized by polyconsumption of both classical drugs and NPS and laboratories supporting emergency rooms, forensic toxicologies and police forces must be enabled to identify the substance/s causing the acute or chronic intoxication or a fatality.