The Metabolism and Detection of New Psychoactive Substances and Emerging Drug Threats in a Poly-drug Context

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Context of the project:934 drug related deaths were recorded in Scotland in 2017, the highest rate reported in Europe and nearly 3 times that recorded in England and Wales. Almost all deaths involved poly-drug abuse and the most common substances involved are opiates and opioids (e.g. heroin and methadone); benzodiazepines (e.g. etizolam and diazepam) and gabapentinoid drugs (gabapentin and pregabalin). Drug users state that gabapentanoids are taken prior to heroin (a mixture of paracetamol, caffeine and diamorphine) to heighten and prolong the effects of the heroin. The mechanism of this reported effect is currently unknown. Users will also take large amounts, often up to 10-30 tablets at a time, of 'street diazepam'. These are illicitly manufactured tablets containing a wide variety of benzodiazepine drugs, often novel drug analogues unlicensed for use in the UK and which are a unique feature of the illicit drug market in Scotland. The drug present, its concentration and its potency will vary widely over time, meaning that users are involved in a form of 'Russian roulette' with the drugs they are taking. When users are tested for drugs using a standard multi-panel drug test field urine test device, they often provide a negative urine test result for benzodiazepines even though the client claims to have recently consumed 'street diazepam' tablets suggesting poor cross reactivity with novel compounds.Aims and Objectives:As benzodiazepines are implicated in so many drug related deaths the project also investigates the development of rapid field test methods to distinguish between the different types of benzodiazepines in 'street diazepam' tablets utilising both classical colorimetric and novel technological solutions. It will also assess the limits of detection and selectivity of commonly used urine test kits forThe aim of this project is to use advanced mass spectrometry detection techniques (quadrupole time of flight (QToF-MS/MS) and triple quadrupole (QQQ-MS/MS) tandem mass spectrometry instruments to investigate the metabolism, co-metabolism or inhibition of metabolism of commonly abused drugs to assess the metabolic impact of co-ingestion of these substances on users. The analytical techniques are developed to determine if specific toxic metabolites are formed and the project will validate measurement methods for their detection if present. Novel physical sciences/engineering aspects of the projectAdvanced mass spectrometry is normally applied in the pharmaceutical industry and drug discovery to investigate drug interactions between legal substances which might be co-prescribed or ingested but is rarely applied to the study of drug interactions between pharmaceutically produced drugs and illicitly produced novel drugs of the types in this study. It will adapt and optimise the existing methodologies to new applications.There are currently no commercially available field tests to rapidly distinguish between closely benzodiazepine drugs and the urine test kits currently being used by front-line staff are not fully validated for the detection of novel benzodiazepines. This project aims to assess the performance of such kits in a polydrug context and to investigate both simple colourometric techniques and novel technologies.