The 2015 amendment to the Road Traffic Act 1988 introduced statutory threshold limits for seventeen controlled substances, creating a need for reliable and efficient methods for in-situ screening of individuals suspected of driving under the influence of drugs. This research evaluates the analytical capability of a single quadrupole mass spectrometer (Waters Acquity QDa) for this application.

Initial experimental work characterised the QDa system to establish a baseline for comparison with subsequent studies using loop injection-electrospray ionisation (LI-ESI) and solvent standards. Optimisation of cone voltage and diluent composition enhanced ionisation efficiency, while in-source fragmentation generated three diagnostic ions per analyte, improving specificity. The method exhibited excellent linearity (R² > 0.99) with limits of detection all below legislative thresholds (0.75-20 ng mL^-1). Repeatability was consistent (RSD < 15%), though intra-day variability indicated the need for an internal standard to correct for instrumental drift.

To assess the feasibility of deployable analysis, two ambient ionisation (AI) techniques were investigated: atmospheric solids analysis probe and thermal desorption, both based on atmospheric pressure chemical ionisation (APCI). Four substrate materials were evaluated, with aluminium foil yielding the best performance following pre-treatment. Plasma and artificial saliva samples were analysed to assess matrix effects. Despite optimisation, sensitivity remained low (10->10,000 ng mL⁻¹), suggesting that the limitation lay primarily with the AI techniques rather than the QDa system itself.

A miniaturised pipette-tip solid-phase extraction (PT-SPE) method was developed for artificial saliva and combined with LI-ESI-QDa analysis. Directly spiked samples processed by PT-SPE showed improved selectivity, reduced matrix effects, and enhanced sensitivity. Although morphine displayed non-linearity (R² < 0.99), specificity remained adequate for screening. Limits of detection (1.6-13 ng mL⁻¹) were below legislative thresholds, demonstrating the potential of miniaturised sample preparation and compact mass spectrometry techniques for drug detection in driving-related offences. These findings support the possible application of such systems within forensic toxicology.