Chapter 15: Comprehensive gas chromatography-mass spectrometry

The complex chemical composition of exhaled breath presents a real analytical challenge, especially for untargeted screening. Indeed, to ensure appropriate fingerprinting of a sample, high resolving power is required. For many years, 1DGC has been the go-to method for volatile mixture characterization. When untargeted resolution of complex samples is required, however, the resolution of the technique reaches its limits. Pushing forward the resolution limitations, GCx GC is the emerging solution. GC xGC relies on the combination of multiple chromatographic dimensions, which can be hyphenated with HRMS. The resulting system allows full sample resolution with a high confidence in compound identification. Nevertheless, such analytical power comes with an increased complexity in
method optimization and data handling. For each data point collected, two retention times and a full (HR) mass spectrum is collected at a rate of 100-200 data points per second. So, there is a growing importance in the use of powerful computer tools to assist optimization and high-dimensional data management. The recent efforts to overcome these complications are making GC xGC the method of choice for untargeted volatilomics. In recent years, several successful studies using GC GC have been conducted for different pathologies. In the complex field of cancer research, for example, the use of exhaled breath represents a real hope for large-scale population screenings. Different proof-of-concept and optimization studies have been successfully conducted in cancer research. The resolution power of GC xGC has been compared to classical 1DGC studies in different fields. For asthma characterization, different research projects are pushing the use of GC GC to diagnose and understand lung inflammation. The first large-scale study combining the output of both GC-MS and GCx GC-HRTOFMS has been conducted for discovery and validation of breath volatiles. Moreover, much effort is being devoted to infectious disease detection, with the aim to complement time-consuming culture-based diagnosis.