Objectives

The MET-A-FOR project deliver research training in advanced and novel analytical techniques which can identify the misuse of prohibited drugs of abuse in bovine and equine animals. This 48 month project will involve 2 beneficiaries – 1 commercial SME, Irish Diagnostic Laboratory Services (IDLS), who specialise in the delivery of diagnostic services to the veterinary sector, and 1 academic, Queen’s University Belfast (QUB) who is a recognized expert in the field of metabolomics – from 2 EU member states – the Republic of Ireland and the UK. This collaboration will facilitate complementary intersectoral knowledge, skills and technology to be used to develop and train 3 early stage researchers (ESRs) to PhD level with the technical capability to effectively apply emerging metabolomic-based techniques and concepts to meet the continuing challenges in chemical residue testing required for food safety, animal welfare and competition integrity enforcement both within Europe and also globally. The research approach in MET-A-FOR will be based on planned intersectoral and multidisciplinary collaborative research facilitated by the establishment of 3 distinct and connected ESR Individual Research Projects with defined research objectives and performed under the joint supervision of academic and non-academic specialists from QUB and IDLS.

ESR 1: Utilisation of in vitrostrategies to rapidly predict metabolism and elimination kinetics of emerging anabolic drugs in sport and food animals

ESR 2:  Metabolomic profiling of urine / plasma responses to illicit drugs of abuse by high resolution mass spectrometry

ESR 3:  Development of integrated screening and targeted advanced mass spectrometry techniques for detection of emerging anabolic drugs of abuse

The outputs from these 3 ESR Fellow PhD projects will ultimately construct an innovative analytical approach to detect the abuse of emerging designer compounds and form the basis of a commercially applicable forensic test based on combined biological/chemical detection comprising of:

1. Preliminary high-throughput untargeted screening of urine/plasma samples to identify biological metabolomic/metabolite signature profiles indicative of designer agent compound use in animals
2. Confirmatory targeted analysis of screened suspect samples to identify the presence of designer compounds and associated drug metabolites in test samples.

The EU is committed to eliminating the use in animals of substances of abuse such as growth promoters, hormones, antibiotics and other drugs, and as such their use is banned with this prohibition also applying to imports from third countries. However, issues surrounding the administration of drugs to animals destined for food production or performance sports continues to be an enormous challenge to regulatory authorities charged with enforcing this ban. The clear economic and competitive advantage to be achieved from their use ensures that illegal administration continues. As an example, despite the fact that all member states are required by legislation to implement a screening and testing program to identify and eliminate banned substance use in food production (Directive 1996/23/EC), it is estimated that up to 10% of European cattle may be treated with illegal substances. Within equine performance sports more drugs are in fact prohibited than in human sports due to the different approaches of the agencies/governing bodies involved in that agents are banned based on their potential effect on a range of biological systems rather than by compound group or class – this significantly increases the range of drugs required to be tested for and also the challenges to be met in detecting them. However, an emerging and worrying source of new drugs of abuse in animals originates from the pharmaceutical sector which develops chemicals for human therapeutic use in a range of clinical conditions. The biological activity and favourable pharmacologic attributes of many of these compounds, such as oral bioavailability and short half-life properties, which facilitates their use in humans, also makes them ideal candidates for illegal application in performance or food-producing animals – sectors of key economic and societal importance to the EU.

The EU has a strategically important global position in terms of beef and dairy animal production. The beef chain in Europe is currently valued at over €80 billion accounting for approx 10% of EU agricultural output. The dairy sector accounts for 13% of EU turnover in the total food and drink industry transforming nearly 150 billion litres of raw milk annually from approximately 1 million farms into a broad range of products which are an essential and functional contribution to the diet of all EU consumers. Maintaining confidence in the integrity and safety of food supply chains is also essential for important EU export markets such as infant formula (e.g. the Republic of Ireland produces 20% of the total world supply of baby milk formula). Additionally, the European Horse Network (EHN) estimates that the total economic impact of the wider equine sector to the EU is valued at €100 billion annually and the maintenance of the reputational standing and integrity of European horse breeders and equine sport is equally important.

As the EU continually tightens regulations and enforcement policies, those carrying out illegal practices involving banned substance use have found ways of both concealing their activities and avoiding detection by current testing regimes. Present testing systems are compromised not only by the use of endogenous hormones and low dose chemical cocktails, but also by the emergence of new designer drugs typically arising from compounds developed primarily to treat various medical conditions in humans. One such class of compounds are known as Selective Androgen Receptor Modulators (SARMs).