Drugs in oral fluid – an evaluation of the release of cocaine and cocaine derivatives from oral drug depots into oral fluid.

Oral fluid (OF) drug testing has been implemented in several countries including the UK for the screening and confirmatory analysis of drugs of abuse (Wille et al. 2009, Chu et al. 2012, Vindenes et al. 2012, UK Goverment 2014). OF testing offers advantages of being non-invasive, less infectious, less likely of being adulterated and simplified collection of samples compared to other matrices such as blood. However, there are still some concerns about the interpretation of the results from OF drug testing related to variation in the concentration of drugs and/or metabolites in OF in comparison with blood. The considerably higher concentrations of some drugs in OF than their respective concentrations in blood could be explained by the release of drugs from oral drug depots into OF (Huestis and Cone 2004). The work described in this thesis aimed at enhancing the existing knowledge on the release of cocaine and cocaine related compounds from oral drug depots into OF and evaluating alternative techniques for the detection of drugs in OF and biological tissues. To accomplish this, the kinetics of release of cocaine and cocaine derivatives were investigated using an in-vivo and an in-vitro model. The in-vivo study evaluated the release of cocaine and derivatives from drug depots into OF by measuring the concentration of these analytes in collected OF samples from human participants that ingested or swirled a cup of coca tea. The in-vitro model evaluated the release using an adapted test system for studying the transport of drugs across biological membranes, Franz diffusion cells, applied on porcine oral tissue and synthetic oral fluid. Classical and alternative techniques such as liquid chromatography and Raman spectroscopy were evaluated for the analysis of cocaine and cocaine derivatives in OF and porcine oral tissue. The research offered new insights into the present knowledge on the release of cocaine and derivatives from drug depots into OF and presented an alternative non-invasive technique for analysing cocaine in OF and tissues. The findings of the research have also contributed to the interpretation of results from OF drug testing. The in-vivo release of drugs from drug depots showed differences in release profiles and windows of detection for cocaine, BZE, EME and AEME following the consumption of coca tea. Windows of detection varied between analytes and indicated that the concentration of drugs in OF was the contribution of the release of drugs from drug depots and the systemic circulation. The in-vitro release of drugs indicated that analytes were released into OF at different rates depending on the physicochemical characteristics of the molecules. Alternative techniques for analysing cocaine in biological matrices included the use of Raman microscopy which could detect cocaine at nanogram levels. The present research is beneficial to regulatory agencies in regard to the analysis of cocaine, the windows of detection, the false positives obtained following ingestion of coca tea and alternative techniques for on-side OF drug testing.