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Detection and characterization of metabolites resulting from polyconsumption of drugs

  • Full or part time
  • Application Deadline
    Thursday, April 25, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

Six new fully funded PhD research studentships are offered in the School of Applied Sciences for a 23 September 2019 start. The School is made up of the Departments of Biological and Geographical Sciences, Chemical Sciences and Pharmaceutical Sciences.

There is competition funding for 6 of the 12 research projects advertised. Usually the projects which receive the best applicants are funded.

Successful applicants will receive a fully funded PhD opportunity to explore the metabolites resulting from polyconsumption of drugs. Polyconsumption is a phenomenom that is increasing throughout the world. The detection of biomarkers that aid interpretation of drug intake is essential, and forensic toxicology concerns itself with targeting the most suitable biomarker (drug or metabolite) in the most suitable biological sample using increasingly sensitive and specific methods.

Prior to drug approval, metabolism studies are performed on single drugs after which biomarkers are then adopted as “target analytes” in drug detection assays, with no regard for drug-drug interactions or reactions that might occur between co-consumed drugs. Often overlooked are unique metabolites resulting from co-consumption of multiple drugs or those present in unique scenarios. For example, anhydroecgonine methyl ester indicates that cocaine has been smoked providing important information on the route of administration while the presence of cocaethylene indicates co-consumption of cocaine and ethanol. Targeting cocaethylene is advantageous because it has an extended half-life of elimination (t1/2) compared with cocaine, and is not subject to problems such as evaporation or microbial and post-mortem production compared with alcohol. Therefore, the metabolite offers analytical and interpretative advantages not possessed by its parent drugs. Furthermore, detection of these unique metabolites can provide vital information on toxicities, and also assist medical professionals in determining cause and manner of death.

In this study, in vitro metabolism will be conducted using commonly-encountered drug combinations incubated with metabolic enzymes such as Cytochrome P450, Carboxylesterase enzymes, and human liver microsomes. Liquid chromatography-mass spectrometry will be employed using product ion scanning, precursor ion scanning and selected reaction monitoring to determine new candidates for the detection of polyconsumption. Precursor ion scanning will enable screening for metabolites based on shared molecular characteristics with the parent drug. Time-of-flight mass spectrometry may also be performed to assist in determination of molecular structures.

Casework samples (blood and urine) will be selected where combinations of commonly-occurring drugs have been detected, and analysed to determine the prevalence of possible markers of poly-drug poisonings. It is hoped that useful metabolites will be identified that offer promise in determining poly-drug use.

The project will be facilitated by collaboration with the Victorian Institute of Forensic Medicine and the Department of Forensic Medicine, Monash University, Melbourne, Australia.

The studentships are open to citizens of the UK or EU only, and cover the full cost of tuition fees and an annual tax-free bursary of £15,009 for three years (RCUK rates). Successful applicants will have a very good first or upper second degree or Masters degree in a relevant subject. The course will begin in September 2019.

To apply, please send your CV and a personal statement to . Please indicate that you wish to apply for the project above and highlight Dr Sophie Turfus, as the supervisor. Please note that the deadline for applications is 25 April 2019.

Please contact Sophie Turfus () for enquiries on the project.

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