A new strategy based on real-time secondary electrospray ionization and high-resolution mass spectrometry to discriminate endogenous and exogenous compounds in exhaled breath

Abstract

Breath is considered to be an easily accessible matrix, whose chemical composition relates to compounds present in blood. Therefore many metabolites are expected in exhaled breath, which may be used in the future for the development of diagnostic methods. In this article, a new strategy to discriminate between exhaled endogenous metabolites and exhaled exogenous contaminants by direct high-resolution mass spectrometry is introduced. The analysis of breath in real-time by secondary electrospray ionization mass spectrometry allows to interpret the origin of exhaled compounds. Exhaled metabolites that originate in the respiratory system show reproducible and significant patterns if plotted in real-time (>1 data point per second). An exhaled metabolite shows a signal that tends to rise at the end of a complete (forced) exhalation. In contrast, exogenous compounds, which may be present in room air, are gradually diluted by the air from the deeper lung and therefore show a trend of falling intensity. Signals found in breath by using this pattern recognition are linked to potential metabolites by comparison with online databases. In addition to this real-time approach, it is also shown how to combine this method with classical analytical methods in order to potentially identify unknown metabolites. Finally exhaled compounds following smoking a cigarette, chewing gum, or drinking coffee were investigated to underline the usefulness of this new approach.