A European proposal for quality control and quality assurance of tandem mass spectral libraries

Abstract

Background: High resolution mass spectrometry (HRMS) is being used increasingly in the context of suspect and non-targeted screening for the identification of bioorganic molecules. There is correspondingly increasing awareness that higher confidence identification will require a systematic, group effort to increase the fraction of compounds with tandem mass spectra available in central, publicly available resources. While typical suspect screening efforts will only result in tentative annotations with a moderate level of confidence, library spectral matches will yield higher confidence or even full confirmation of the identity if the reference standards are available. Results: This article first explores representative percent coverage of measured tandem mass spectra in selected major environmental suspect databases of interest in the context of human biomonitoring, demonstrating the current extensive gap between the number of potential substances of interest (up to hundreds of thousands) and measured spectra (0.57–3.6% of the total chemicals have spectral information available). Furthermore, certain datasets are benchmarked, based on previous efforts, to show the extent to which acquired experimental data were comparable between laboratories, even with HRMS instruments based on different technologies (i.e., quadrupole–quadrupole-time of flight versus ion trap/quadrupole-Orbitrap). Instruments and settings that are less comparable are also revealed, primarily linear ion trap instruments, which show distinctly lower comparability. Conclusions: Based on these efforts, harmonization guidelines for the acquisition and processing of tandem mass spectrometry data are proposed to enable European (and ideally worldwide) laboratories to contribute to common resources, without requiring extensive changes to their current in house methods.