High-quality identification of volatile organic compounds (VOCs) originating from breath
Wisenave Arulvasan, Hsuan Chou, Julia Greenwood, Madeleine L. Ball, Owen Birch, Simon Coplowe, Patrick Gordon, Andreea Ratiu, Elizabeth Lam, Ace J. Hatch, Monika Szkatulska, Steven Levett, Ella Mead, Chloe Charlton-Peel, Louise Nicholson-Scott, Shane Swann, Frederik‐Jan van Schooten, Billy Boyle, Max Allsworth
Abstract
INTRODUCTION: Volatile organic compounds (VOCs) can arise from underlying metabolism and are detectable in exhaled breath, therefore offer a promising route to non-invasive diagnostics. Robust, precise, and repeatable breath measurement platforms able to identify VOCs in breath distinguishable from background contaminants are needed for the confident discovery of breath-based biomarkers. OBJECTIVES: To build a reliable breath collection and analysis method that can produce a comprehensive list of known VOCs in the breath of a heterogeneous human population. METHODS: platform, consisting of sample collection, TD-GC-MS analysis and feature extraction was utilized. VOCs were determined to be "on-breath" if they met at least one of three pre-defined metrics compared to paired background samples. On-breath VOCs were identified via comparison against purified chemical standards, using retention indexing and high-resolution accurate mass spectral matching. RESULTS: 1471 VOCs were present in > 80% of samples (breath and background), and 585 were on-breath by at least one metric. Of these, 148 have been identified covering a broad range of chemical classes. CONCLUSIONS: A robust breath collection and relative-quantitative analysis method has been developed, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. Providing confirmed VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. Additionally, this list of VOCs can be used to facilitate cross-study data comparisons for improved standardization.