We report on the search for low molecular weight molecules-possibly accumulated in the bloodstream and body-in the exhaled breath of uremic patients with kidney malfunction. We performed non-invasive analysis of the breath gas of 96 patients shortly before and several times after kidney transplantation using proton-transfer-reaction mass spectrometry (PTR-MS), a very sensitive technique for detecting trace amounts of volatile organic compounds. A total of 642 individual breath analyses which included at least 41 different chemical components were carried out. Correlation analysis revealed one particular breath component with a molecular mass of 114 u (unified atomic mass units) that clearly correlated with blood serum creatinine, which is the currently accepted marker for assessing the function of the kidney. In particular, daily urine production showed good correlation with the identified breath marker. An independent set of seven samples taken from three patients at the onset of dialysis and three controls with normal kidney function confirmed a significant difference in concentration between patients and controls for a compound with a molecular mass of 114.1035 u using high mass resolving proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS). A chemical composition of CHO was derived for the respective component. Fragmentation experiments on the same samples using proton-transfer-reaction triple-quadrupole tandem mass spectrometry (PTR-QqQ-MS) suggested that this breath marker is a C-ketone or a branched C-aldehyde. Non-invasive real-time monitoring of the kidney function via this breath marker could be a possible future procedure in the clinical setting.

<p><span style="color: rgb(0, 0, 0); font-family: Arial, Helvetica, Verdana, sans-serif; font-size: 12px; line-height: 16.1875px; background-color: rgb(255, 255, 255);">We analysed the time evolution of several volatile organic compounds formed by the catabolism of ingested isotope-labelled ethanol using real-time breath gas analysis with proton-transfer-reaction mass spectrometry. Isotope labelling allowed distinguishing the emerging volatile metabolites from their naturally occurring, highly abundant counterparts in the human breath. Due to an extremely low detection limit of the employed technologies in the parts per trillion per volume range, it was possible to detect the emerging metabolic products in exhaled breath within ~10&nbsp;min after oral ingestion of isotope-labelled ethanol. We observed that ethanol was in part transformed into deuterated acetone and isoprene, reflecting the different fates of activated acetic acid (acetyl-coenzyme A), formed in ethanol metabolism. Using ethanol as a model clearly demonstrated the value of the here presented technique for the search for volatile markers for metabolic disorders in the exhaled breath and its potential usefulness in the diagnosis and monitoring of such diseases.</span></p>

Proton transfer reaction-mass spectrometry (PTR-MS) is a well-established analytical tool for the measurement of volatile organic compounds (VOCs), and offers real-time detection and quantification of VOCs at trace concentrations. This paper focuses on the measurement of VOCs in biological systems. Both microorganisms and cells, e.g., in the human body, constantly produce a large variety of volatile organic metabolites. Analyzing VOCs in exhaled human breath reveals information about the status of the body. In a similar manner, monitoring the off-gas of fermentations in the biopharmaceutical industry allows microbial activity to be gauged. Undesired compounds (those that are harmful to the human body or impurities in biotechnical processes) can also be tracked in real time using the technique.

We present a novel method for real-time breath-gas analysis using mass-spectrometric techniques: buffered end-tidal (BET) on-line sampling. BET has several advantages over conventional direct on-line sampling where the subject inhales and exhales through a sampling tube. In our approach, a single exhalation is administered through a tailored tube in which the end-tidal fraction of the breath-gas sample is buffered. This increases sampling time by an order of magnitude to several seconds, improving signal quality and reducing the total measurement time per test subject. Furthermore, only one exhalation per minute is required for sampling and the test subject can otherwise maintain a normal breathing pattern, thereby reducing the risk of hyperventilation. To validate our new BET sampling method we conducted comparative measurements with direct on-line sampling using proton-transfer-reaction mass spectrometry. We find excellent agreement in measured acetone and acetonitrile concentrations. High variability observed in breath-by-breath isoprene concentrations is attributed to differences in exhalation depth and influences of hyperventilation on end-tidal concentrations.