E!10628 Psychomics - New psychoactive substances and their metabolites

WP 1: Project management Leverbar oppdatering av resultatene er som angitt nedenfor. WP 2: Exploitation and Dissemination Arrangerte det tredje internasjonale symposiet om NPS sammen med Nal-von-Minden i London 29. - 30. november 2018 med 107 deltakere. Forelesninger var gitt av 6 Chiron-LiU deltagere. Deltok på TIAFT 2019-konferanse i august / september. 2019 i Birmingham, Chiron og Liu har to muntlige presentasjoner. WP 3: Specifications and Market Survey En Liste over målanalyser og produkter oppdateres kontinuerlig. Markeds undersøkelse utføres kontinuerlig basert på innspill fra kunder. Etter en rettsavgjørelse i Sverige som effektivt avsluttet nettbutikker, har forekomsten av NPS-medikamenter falt betydelig i rapporteringsperioden. Dette kan være midlertidig, men for å sikre at det er tilgjengelig autentiske prøver og informasjon, undersøker vi muligheten for å bruke andre kilder. WP 4: Development of Analytical Methods Etikettsøknaden for systematisk innsamling og lagring av positive urinprøver ble godkjent, metodikken for hvordan man effektivt kan identifisere og dele prøver er under utvikling. WP 5: Metabolic Studies with human liver microsomes Hepatocytteksperimenter ble gjentatt for fentanylanaloger og cannabinoider og identifiserte metabolitter sammenlignet med syntetiserte referansematerialer. Utvikling av data pågår. WP 6: Synthesis of NPS standards and metabolites Resultater fra Chiron fra 1.mai 2018 til 31. oktober 2018: 31 forbindelse er syntesitert SPICE forbindelser: 19 innfødte Amfetamin: 2 native, 1 deuterium-merket Cathinones: 1 native, 1 deuterert Fentanyls: 4 native, 1 deuterert Amfetamin: 2 native Benzodiazepiner: 2 native Cocaines: 1 native Resultater fra Chiron 31. august 2018 til 31. august: 69 forbindelser SPICE forbindelser: 28 native, 1 deuterert Amfetamin: 11 innfødte Cathinones: 6 native, 1 deutererte Fentanyls: 6 native, 1 deuterert Benzodiazepiner: 4 native, 1 deutererte Tryptaminer: 2 native Opiater: 4 native, 2 deutererte Peth: 1 native, 1 deuterert Totalt sett har Chiron syntetisert 280 NPS-produkter som referansemateriell, inkludert 242 naturlige produkter, 31 deutererte og 6 13C-merkede forbindelser. 6 fentanylmetabolitter og 1 kryddermetabolit er blitt syntetisert ved Linköpings universitet fra 1. mai 2018 til 31. oktober 2018. Totalt sett har prosjektet levert 47 metabolitter av fentanyler, 5 av dem er oppskalert. 2 metabolitter Krydderforbindelser er også blitt syntetisert. WP 7: Certification of reference materials Chiron mottatt ISO / IEC 17025: 2017 akkreditering i Desember 2018.

In overall, a total of 280 NPS have been produced at Chiron in the project, including 243 native NPS as reference materials, 13 deuterated and 6 13C-labelled analoges as internal standards for NPS analysis and monitoring. Metabolic study was performed at Linkjøping University, metabolites of fentanyls and fentanyl derivatives and synthetic cannabinoids were identified, and total 50 metabolites were synthesized as references for the study, 5 of them were scale-up as reference materials. PSYCHOMICS marketable products are a wide range of CRMs for both new NPS native compounds and associated metabolites, empowering analysts world-wide to monitor and control the distribution and use of NPS. With the outcome of NPS reference materials and deuterated, 13C-labelled reference materials developed in the project, Chiron has now a stronger and more competitive marked position for supply CRM for forensic toxicology.

NPS, also known as designer drugs or legal highs, have been emerging onto the recreational drug scene at an unprecedented rate, with 101 new compounds reported in 2014 alone. Thus to keep up to this pace, new reference methods and materials are required to enable accurate detection of drug use for law enforcement authorities an forensic toxicology institutions, not only to provide criminal evidence but also to link these unregulated substances to severe health events and deaths. Despite CRMs for monitoring and control the distribution and the use of NPS, have been introduced alongside with robust analytical methods, the rate at which new NPS compounds emerge significantly outpaces the development of counterpart ref. materials for efficient monitoring and testing of these substances. This is a key driver for the main project goal: to develop a Predictive Parallel Production Platform (P4), which will allow to significantly increase the number of available CRMs for NPS compounds. This novel approach will disruptively shift the current paradigm, which is centered on a reactive development of CRMs after illegal producers introduce them in the market. Instead, the P4 approach relies on an efficient, simultaneous and larger scale synthesis of several compounds, targeting not only already reported NPS, but also those which will likely appear in the market based on chemical similarities. NPS drugs are normally detected in urine using analytical methods such as LC-MS/MS. However, in most cases the intake has to be proven based on metabolite findings, which have longer detection windows as they remain longer in the body. To be able to do this, the identity of the metabolites must be known, which usually is not the case. Thus, the second goal of this project is to improve our understanding of the metabolism of NPS. This project aims for early identification of metabolites originating from novel drugs of abuse, by combining a hepatocytes/microsomes-based processing pipeline