E!10628 Psychomics - New psychoactive substances and their metabolites

WP 1: Project management Deliverable update of results as stated below WP 2: Exploitation and dissemination Arranged the third international symposium on NPS together with Nal-von-Mnden in London November 29-30th 2018 with 107 attendies. Lectures given by 6 Chiron-LiU attendees. Attended TIAFT 2019 conference in Aug/Sep. 2019 in Birmingham, Chiron and Liu have two oral presentations. WP 3: Specification and Market Survey List of target analytes is updated continuously based on customer feedback. Following a court ruling in Sweden effectively shutting down online shops the prevalence of NPS drugs has dropped significantly during the reporting period. This might be temporary but to ensure the available of authentic samples and information we are exploring the possibility of using other sources. WP 4: Development of Analytical Methods The ethics application to systematically collect and save positive urine samples was approved and methodology for how to efficiently identify and aliquot samples is under development. WP 5: Metabolic Studies with human liver microsomes, hepacytes and/or authentic case samples. Hepatocyte experiments were repeated for fentanyl analogs and cannabinoids and identified metabolites compared to synthesized reference materials. Data eveluation is ongoing. We have also tested 14 fentanyl analog metabolites against hepatocyte samples and/or urine samples to test if they are in fact identical to observed metabolites in vivo. WP 6: Synthesis of NPS standards and metabolites Results from Chiron from 1. Mai 2018 to 31. october 2018: 31 compounds (NPS standards and metabolites) Spice compounds: 19 native NBOMes/Amphetamines: 2 native, 1 deuterium labelled Cathinones: 1 native, 1 deuterated Fentanyls: 4 native, 1 deuterated Amphetamines: 2 native Benzodiazepines: 2 native Cocaines: 1 native Results from Chiron from 31. Aug 2018 to 31. Aug: 69 compounds Spice compounds: 28 native, 1 deuterated Amphetamines: 11 native Cathinones: 6 native, 1 deuterated Fentanyls: 6 native, 1 deuterated Benzodiazepines: 4 native, 1 deuterated Tryptamines: 2 native Opiates: 4 native, 2 deuterated Peth: 1 native, 1 deuterated In overall, Chiron has synthesized 280 NPS products as reference materials, including 242 native products, 31 deuterated and 6 13C-labelled compounds. 6 fentanyl metabolites and 1 Spice metabolite have been synthesized at Linköping University from 1. Mai 2018 to 31. october 2018. In overall, the project has delivered 47 metabolites of fentanyls, 5 of them have been scaled up. 2 metabolites Spice compounds have also been synthesized. WP 7: Certification of reference materials Chiron received ISO/IEC 17025:2017 accreditation in December 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