Analysis of Volatile Organic Compounds in Expired Air in Healthy Volunteers: Comparison of Three Mass Spectrometry Techniques for the Characterization of Volatolome in Clinical Studies

A major obstacle in precision medicine is the unavailability of biomarkers that are easy to access, non-invasive, measurable with high-performance techniques, fast, easy to use, reproducible, inexpensive and easily deployable on a large scale. The analysis of exhaled air (volatolomics) is an "omics" approach devoted to the analysis of volatile organic compounds (VOCs) eliminated by the pulmonary route with real-time detection, at the patient's bedside. The reference technology for the analysis of VOCs is mass spectrometry (MS). Several types of mass spectrometers can be used, and, in the absence of a consensual and standardized method, have practical methods for carrying out different analyzes which also lead to the generation of specific signals whose nature, complexity and exhaustiveness of information generated are heterogeneous. The clinical studies carried out to date use one of the analytical techniques available, without the choice necessarily being guided by objective factors. The objective of this study is to fill this gap and compare the information obtained by three mass spectrometry techniques available to our team (proton transfer reaction - mass spectrometry (PTR-MS), Soft Ionization by Chemical Reaction in Transfer (SICRIT) , two-dimensional gas chromatography-mass spectrometry (GCxGC-MS)) for volatolome analysis. The comparative analysis of the different signals will make it possible to determine the interests and limits of each technique and thus to direct preferentially towards one, the other, or combinations of them for the realization of future clinical studies. One of the main challenges also consists in establishing the concordance of the signals generated by the different technological approaches, some employing prior chromatographic separation, others not, and some employing soft ionization methods while those of others are on the contrary hard. Thus, the availability of datasets obtained on the same population with these complementary approa