Proton-transfer-reaction mass spectrometry (PTR-MS) is a convenient technique for fast analysis of exhaled breath without prior sample preparation. Since compounds are not separated prior to analysis as in gas chromatography mass spectrometry (GC-MS), and since protonated molecules may fragment, relatively complex spectra may arise, which are not easily interpreted in a quantitative way. We calibrated 21 different compounds of importance for exhaled breath analysis, based on the respective pure standards diluted with nitrogen. These calibration measurements included determination of the fragmentation pattern of each compound under dry conditions and in the absence of CO₂. Even though the fragmentation pattern may be predicted in a qualitative manner, the quantitative details may depend on water and CO₂ content. This is exemplarily shown for isoprene. Out of the selected 21 compounds, 11 compounds showed substantial fragmentation (fragments proportion > 10%). Fragmentation of several volatile organic compounds (VOCs) in the drift tube of PTR-MS has been previously observed (Buhr et al 2002 Int. J. Mass Spectrom. 221 1–7; Taipale et al 2008 Atmos. Chem. Phys. Discuss. 8 9435–75; Hewitt et al 2003 J. Environ. Monit. 51–7; Warneke et al 2003 Environ. Sci. Technol. 37 2494–501; de Gouw and Warneke 2007 Mass Spectrom. Rev. 26 223–57; Pozo-Bayon et al 2008 J. Agric. Food Chem. 56 5278–84) and calibration factors for several compounds at corresponding mass-to-charge ratios have been calculated. In this paper, besides the calibration factors, the proportions of substantial fragments are also taken into account for a correct quantification in the case of overlapping signals. The spectrum of a mixture of the considered 21 compounds may be simulated. Conversely, the determination of concentrations from the spectrum of such a mixture is a linear optimization problem, whose solution is determined here using the simplex algorithm.