The Continuous Evolution of the Illicit Benzodiazepine Drug Market in Scotland: Detection, Profiling and Risk Assessment

Scotland has one of the highest drug-related death rates in the world. However, despite benzodiazepines being identified as one of the most commonly implicated compounds in Scottish drug-related deaths, there is currently a paucity of information relating to the types, dosages, and formats of benzodiazepines in the Scottish community. Community drug checking has been proposed as a harm reduction method in Scotland, but the lack of relevant analytical data makes it challenging to develop methods for the detection of these compounds. The aim of this thesis is to develop a template for point of care drug checking techniques for the identification of benzodiazepines, using non-judicial samples seized from Scottish prisons as an example dataset. The data from the Scottish prisons were found to provide an accurate representation of the types of benzodiazepines encountered in the general Scottish community when compared to findings reported in general and national statistics reports. Evaluation of three ion mobility spectrometry (IMS) instruments for the detection of 15 benzodiazepine-type compounds revealed that IMS can be used as a simple-to-use, rapid and highly sensitive means of detecting benzodiazepines. However, these data also revealed that the unequivocal identification of benzodiazepine-type compounds using IMS can be challenging. Development of a HPLC method for the qualitative analysis of benzodiazepine-type compounds showed that HPLC can be used for the accurate identification of benzodiazepines, and when used concurrently with IMS, can improve the confidence and certainty in reporting results obtained at the point of care. The recommendation is that in-situ methods at the point of care, IMS combined with HPLC, should be supported by accurate quantitative data to ensure continued calibration of instruments and development of analytical procedures. This can be achieved with the point of care being supported by a back-of-house laboratory. A quantitative method for etizolam, using gas chromatography-mass spectrometry, was developed, validated, and applied to 192 seized samples. These data demonstrated variability in the concentration of etizolam, both between and within drug formats. Finally, this research highlighted the need for an appropriate data management strategy to reduce the time required to analyse the quantitation of unknown samples, and a semi-automated data processing method was developed to handle the data generated in this work.