Real-Time Quantification of Amino Acids in the Exhalome by Secondary Electrospray Ionization-Mass Spectrometry: A Proof-of-Principle Study

Amino acids are frequently determined in clinical chemistry. However, current analysis methods are time-consuming, invasive, and suffer from artifacts during sampling, sample handling, and sample preparation. We hypothesized in this proof-of-principle study that plasma concentrations of amino acids can be estimated by measuring their concentrations in exhaled breath. A novel breath analysis technique described here allows such measurements to be carried out in real-time and noninvasively, which should facilitate efficient diagnostics and give insights into human physiology. The amino acid profiles in 37 individuals were determined by ion-exchange HPLC in blood plasma and simultaneously in breath by secondary electrospray ionization coupled to high-resolution mass spectrometry. Participants were split into training and test sets to validate the analytical accuracy. Longitudinal profiles in 3 individuals were additionally obtained over a 12-h period. Concentrations of 8 slightly volatile amino acids (A, V, I, G, P, K, F, Orn) could be determined in exhaled breath with a CV of