Novel strategies for online detection of doping compounds in breath using secondary electrospray ionization mass spectrometry
Lukas Christian Meier
Abstract
It has been known for years that breath analysis has the potential of becoming a powerful tool to acquire information on the health status of individuals. Using mass spectrometry (MS) for breath analysis would allow for the detection of hundreds of compounds simultaneously and even render real time (online) monitoring of the individual’s health status possible. Unfortunately, the efficient transfer of breath into mass spectrometers is difficult to achieve. Therefore, only very volatile organic compounds (VOCs) being present in breath at high concentrations have been measured so far. The work presented in this thesis intends to extend the range of compounds being detected in breath towards higher masses, less volatile and less concentrated compounds. In order to achieve this, an ion funnel interface has been designed to allow for a more efficient ion transfer from the ambient pressure region in front of the instrument into the low pressure region within the MS. In a first step, the capabilities of the ion funnel interface was tested. It was found that for both extractive electrospray ionization (EESI) and secondary electrospray ionization (SESI) the sensitivity could be increased by up to three orders of magnitude when using semi-volatile compounds such as salbutamol, cocaine and atenolol. In a second step, a breath interface was developed that could be mounted to the ion funnel interface. Here, it could be shown that this newly built interface allows for the detection of dozens of compounds that cannot be detected while doing breath analysis with neither the ion funnel nor the breath interface. In an independent study, it was investigated how and to what extent internal standards could be used to acquire quantitative information on compounds in breath. It was found that with present knowledge, quantitative results have to be interpreted carefully as even signals of chemically very similar compounds can be influenced tremendously depending on what other compounds are present in breath. The development of a breath interface ion funnel (BIIF) interface accomplished in this thesis allows the analysis of compounds of masses of up to 500 Daltons in breath for the first time, paving the way for screening studies that search for biomarkers in breath.
