Rapid In Vivo Fingerprinting of Nonvolatile Compounds in Breath by Extractive Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry
H. Chen, A. Wortmann, W. Zhang, and R. Zenobi
Abstract: Quantitative analysis of trace constituents in exhaled gas can provide useful insights into biochemical processes in the body, thus revealing information about metabolic dynamics and providing, theoretically, a scientific base for biomarker research or clinical diagnoses. Breath, however, is rarely used practically for diagnostic purposes in clinical medicine because of analytical difficulties. Numerous attempts have been made for fast breath analysis by using methods that include proton transfer reaction mass spectrometry (PTR-MS), selected ion flow tube (SIFT) mass spectrometry, and exhaled breath condensate (EBC) analysis, the latter being based on chromatographic separation. However, these methods require tedious sample collection and sample pretreatment procedures. PTR-MS and SIFT-MS have been used for direct breath analysis, but require specially designed instruments that are not widely available.
To date, only low molecular-weight compounds (up to ca.100 Da), almost exclusively volatile species, have been detected in breath. With the exception of SIFT-MS, measurements are also compromised by the high water content in breath. Actually, breath is a type of aerosol, and, in addition to volatile constituents, contains a vast variety of nonvolatile compounds dissolved in the microdroplets. We herein report an extractive electrospray ionization (EESI) quadrupole time-of-flight mass spectrometry (QTOF-MS) method that has been established without modification of a commercial ESI interface for the rapid in vivo fingerprinting of human breath. It presents a direct way to probe the dynamics of body metabolism and a simple, experimentally convenient method for the fast clinical diagnosis of oral malodors, based on fingerprinting of both volatile and nonvolatile trace components in breath without any sample pretreatment.