The ability to utilise in vitro microsomal incubationsto rapidly predict the degradation and metabolite profile of new emerging designer drugs will be the focus of WP2 and will form the core component of IRP1 to be performed by ESR1. The work of this WP will provide a distinct advance towards the rapid development of targeted mass spectrometry detection methods which require prior knowledge of drug metabolism profiles associated with designer drugs and for which time consumingin vivo studies are not feasible. This will be investigated initially using rodent animal models enabling comparison of in vitrometabolism to actual in vivometabolism of SARM compounds. Subsequent studies will compare the in vitrometabolism of designer anabolics by different microsomal preparations (bovine/equine) to assess species-specific activities and determine if one microsomal preparation is sufficient to enable methods to be developed for all species. Due to expertise in the performance of in vitroand access to in vivoexperimental facilities, academic beneficiary QUB will supervise WP2 activities.
Untargeted metabolomic profiling of urine/plasma using high resolution mass spectrometry will be performed in WP3 to examine the biological responses of animals (equine and bovine) treated with anabolic agents and identify biological marker signatures, and will form the core activities of IRP2 to be performed by ESR2. Metabolomic response profiles to anabolic administrations will be assessed in test matrices (urine/plasma) and bioinformatical tools developed to facilitate testing of samples on a high-throughput basis. QUB as leading proponents of the use of metabolomics and expertise in bioinformatical analysis of large datasets will supervise WP3 activities.
Mass spectrometry based analytical techniques (screening and confirmatory) will be developed through WP4to enable measurement of SARM-like chemical metabolites/degradation products in various test matrices (urine/plasma). These research activities will form the core component of IRP3 to be performed by ESR3. Initial work will involve profiling of the metabolites generated from in vitro/in vivo experimental studies with a focus on development of mass spectrometry methods as confirmatory tools for analysis of test-samples, and also on the development of untargeted high-throughput screening methods using qToF-MS profiling approaches. Non-academic beneficiary IDLS with their targeted mass spectrometry method development and validation expertise will supervise WP4 activities.
WP2, 3 and 4 will demonstrate the potential of metabolite/metabolomics approaches to identify the abuse of emerging anabolic SARM compounds in animals and WP5 will integrate the work of the 3 ESR Fellow PhD projects into a single approach to enable development of a forensic test that can be offered on a commercial basis. WP1 will ensure effective management of all aspects of the MET-A-FOR Project based on a transparent management structure and fair decision making procedure. QUB will lead WP1 and co-ordinate and monitor all research, recruitment, financial and administrative activities. WP6will facilitate effective communication between ESR Fellows and ESR Supervisory teams within the project particularly when ESRs are hosted at either the academic or non-academic beneficiaries. WP6 will be led by IDLS who will manage IPR issues within the project and co-ordinate actions aimed at the wider dissemination and communication of the MET-A-FOR project.