Application of Breath Analysis for the Detection of Drugs of Abuse

Human breath is a mixture of gases of which a small part is volatile organic compounds (VOCs), which can either be of endogenous or exogenous origin. This thesis focuses on the exogenous compounds that are metabolized in the human body, their detection in exhaled breath and their possible application as a forensic tool in the detection of drugs of abuse. Online real-time proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) was used for the analysis of breath after having consumed the equivalent of one unit of alcohol as a model system. These experiments showed ethanol could be very quickly detected and its metabolites appeared in the breath profile sometime later, showing the significance of mouth contamination while measuring ethanol via breath. Large differences were also observed when comparing the results between the fasted and non-fasted states of volunteers. Variability of ethanol in the breath profiles was also investigated, showing the importance of biological variation in such studies. The investigation of the ion distribution of alcohols using selective reagent ionization time-of-flight mass spectrometry (SRI-TOF-MS) is presented to better determine breath compounds produced via drug metabolism. The ion distribution of a selection of deuterated compounds was also investigated, showing the attention that needs to be taken when working with such compounds as markers in breath profiles. The PTR-TOF-MS system was applied further for the investigation of a more complex drug of abuse in breath, pseudoephedrine. Breath and blood profiles of drug metabolites were investigated and showed how variable the T_max can be in blood samples, but also the homogeneity of breath profiles between volunteers making it difficult to decipher differences in the data set. Such studies show the challenging aspects of breath analysis as a detection method for drugs of abuse as biological variation is a major confounder. However, whilst the use of breath analysis should be approached with some caution it has potential for future forensic applications.