Identifying Volatile Organic Compounds (VOCs) Originating from Breath with TD-GC–MS

A recent study presented a novel methodology combining robust breath and background collection which analytically distinguished breath volatile organic compounds (VOCs) from background contamination, as well as VOC identification against chemical standards. The researchers, who usedthermo-desorption gas chromatography-mass spectrometry (TD-GC–MS) in their efforts, demonstrated the capability of their method by presenting a list of high-confidence breath VOCs identified from a heterogeneous human population. An article dealing with this research has been published in Metabolomics.

Although metabolomic studies primarily focus on aqueous metabolites in samples such as blood, urine, and feces, breath is a rich and diverse matrix containing thousands of different VOCs (2,3). While the non-invasive nature of breath sampling makes it particularly attractive for clinical applications, such as early diagnosis and ongoing longitudinal monitoring, the validation of clinically useful breath biomarkers remains limited, likely due, at least in part, to the lack of consistent methodologies and quality controls across the breath research literature (4,5). To advance the field of breath analysis, an urgent need is present to develop a robust platform able to accurately identify the VOCs considered to be genuinely originating from the breath, as well as to distinguish these VOCs from those in the background VOCs arising from sampling equipment, as well as surrounding air inhaled immediately by the testing subject before sampling and are thus unrelated to underlying physiology.The team carrying out this research believed that an accurate and repeatable methodology would expedite identification and validation of VOC biomarkers of disease in future studies (1).

Following the analysis of 90 adult breath samples, the authors reported their method to be a success, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. The data confirmed that VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. In addition, the list of VOCs generated can be used to facilitate cross-study data comparisons for improved standardization (1).

It is the hope of the authors to expand the list to include a broad range of populations and physiologies to capture the diversity of on-breath VOCs. By continuing to compare background samples collected and analyzed in the same manner as their breath samples, the team believes that the VOCs able to be confidently identified as being on-breath can be the basis for future biomarker investigations (1).

Young woman breathes out steam outdoor in winter. © illustrisima- stock.adobe.com

References

1. Arulvasan, W.; Chou, H.; Greenwood, J. et al. High-Quality Identification of Volatile Organic Compounds (VOCs) Originating from Breath. Metabolomics 2024, 20. DOI: 10.1007/s11306-024-02163-6

2. Costello, B. L.; Amann, A.; Al-Kateb, H.; Flynn, C.; Filipiak, W.; Khalid, T.; Osborne, D.; Ratcliffe, N. M. (2014). A Review of the Volatiles from the Healthy Human Body. J. Breath Res. 2014, 8 (1), 014001. DOI: 10.1088/1752-7155/8/1/014001

3. Haworth, J. J.; Pitcher, C. K.; Ferrandino, G.; Hobson, A. R.; Pappan, K. L.; Lawson, J. L. D. Breathing New Life into Clinical Testing and Diagnostics: Perspectives on Volatile Biomarkers from Breath. Crit. Rev. Clin. Lab. Sci. 2022, 59 (5), 353–372. DOI: 10.1080/10408363.2022.203807

4. Issitt, T.; Wiggins, L.; Veysey, M.; Sweeney, S. T.; Brackenbury, W. J.; Redeker, K. Volatile Compounds in Human Breath: Critical Review and Meta-Analysis. J. Breath Res. 2022, 16 (2), 024001. DOI: 10.1088/1752-7163/ac5230

5. Jia, Z.; Patra, A.; Kutty, V. K.; Venkatesan, T. Critical Review of Volatile Organic Compound Analysis in Breath and in vitro Cell Culture for Detection of Lung Cancer. Metabolites 2019, 9 (3), 52. DOI: 10.3390/metabo9030052