Comprehensive analysis of exhaled breath VOCs using GC-MS and GC×GC-TOF-MS: a comparative platform evaluation with...

This study presents a comprehensive analytical approach for characterizing volatile organic compounds (VOCs) in exhaled breath using thin film microextraction (TFME) and needle trap device (NTD) sampling, coupled with GC-MS and GC×GC-TOF-MS platforms. A methodological comparison highlighted the distinct capabilities of these two complementary extraction methods for capturing free versus total VOC concentrations, with NTD demonstrating enhanced extraction efficiency for polar compounds. For instance, octanal was detected at significantly higher concentrations using NTD (9.5 ± 1.1 µg L^-1) compared to TFME (6.9 ± 0.8 µg L^-1). The GC×GC-TOF-MS platform demonstrated superior separation capabilities, identifying 28 unique compounds compared to the 17 detected by the conventional GC-MS method. The enhanced resolution of GC×GC-TOF-MS enabled detection of compounds such as 1,3-dimethylbenzene, D-limonene, and 3-carene, previously unresolved using the traditional GC-MS approach. Both platforms exhibited excellent quantitative performance, with relative standard deviations typically below 15%. As a proof of concept, breath samples from six male volunteers (aged 21-39) were analyzed, revealing distinct VOC profiles corresponding to cigarette smoking status. Current smokers (n = 2) exhibited significantly elevated levels of benzene (9.5-12.5 µg L^-1) and styrene (50.1-67.3 µg L^-1) compared to never-smokers (n = 3, benzene: 2.0-3.5 µg L^-1, styrene: 10.4-19.1 µg L^-1). The ex-smoker's profile demonstrated intermediate concentrations of these compounds, suggesting partial recovery of breath chemical composition after smoking cessation. Notably, certain compounds, including 1,4-dimethylbenzene, were exclusively detected in current smokers (1.3-14.6 µg L^-1), while α-pinene showed higher prevalence in never-smokers and ex-smokers (3.0-6.8 µg L^-1). Overall, this methodology provides a robust framework for comprehensive breath analysis, offering insights into both analytical method performance and potential smoking-related biomarkers. The complementary sampling approaches presented in this study enable effective differentiation between free and total VOC concentrations, while the dual-platform analysis ensures reliable compound identification and quantification.