Expanding metabolite coverage of real-time breath analysis by coupling a universal secondary electrospray ionization source and high resolution mass spectrometry—a pilot study on tobacco smokers

Abstract

Online breath analysis is an attractive approach to track exhaled compounds without sample preparation. Current commercially available real-time breath analysis platforms require the purchase of a full mass spectrometer. Here we present an ion source compatible with virtually any preexisting atmospheric pressure ionization mass spectrometer that allows real-time analysis of breath. We illustrate the capabilities of such technological development by upgrading an orbitrap mass spectrometer. As a result, we detected compounds in exhaled breath between 70 and 900 Da, with a mass accuracy of typically <1 ppm; resolutions between m/Δm 22,000 and 70,000 and fragmentation capabilities. The setup was tested in a pilot study, comparing the breath of smokers (n = 9) and non-smokers (n = 10). Exogenous compounds associated to smoking, as well as endogenous metabolites suggesting increased oxidative stress in smokers, were detected and in some cases identified unambiguously. Most of these compounds correlated significantly with smoking frequency and allowed accurate discrimination of smokers and non-smokers.

Applications of Near Infrared Photoacoustic Spectroscopy for Analysis of Human Respiration: A Review

“…In studies on human breath, more than 3000 different VOCs and particles have been detected, where most of the VOCs are at low concentrations, i.e., from ppm to ppb or ppt [81][82][83][84][85][86]. A healthy adult human has a respiratory rate of 12−15 breaths/min at rest, inspiring and expiring 6-8 L of air per minute.…”

“…The most predominant endogenous compounds in breath are isoprene (12-580 ppb), ethanol (13-1000 ppb), methanol (160-2000 ppb), and acetone (1.2-1800 ppb); other alcohols are present in the very low concentration. Only a small number of VOCs are common to everyone (isoprene, acetone, ethane, and methanol) which are products of metabolic processes and some of these VOCs (ethane, n-pentane, butane, ethanol, acetone) have been identified as breath biomarkers [81][82][83][84][85][86].…”

Volatolomics: A broad area of experimentation

“…In personalized healthcare, breath analysis has been demonstrated by clinicians to allow determination of the smoking habits of an individual [107][108][109][110]. Currently, blood and urine analysis of cotinine (a primary metabolic product of nicotine) was used as a diagnostic tool.…”

Oxidative lipidomics: applications in critical care

“…An improved LC-MS method that simplified the extraction and clean-up steps in a simple online column-switching HPLC setup demonstrated identification of 7 prostanoids directly from hepatocytes in a 96 well format [11*]. Similarly, a pilot study demonstrated the possibility of identifying degraded products of oxidized free fatty acids directly from exhaled breath in smokers in a high throughput manner [12*]. …”