Tools for monitoring system suitability in LC MS/MS centric proteomic experiments

With advances in liquid chromatography coupled to tandem mass spectrometry technologies combined with the continued goals of biomarker discovery, clinical applications of established biomarkers, and integrating large multiomic datasets (i.e. "big data"), there remains an urgent need for robust tools to assess instrument performance (i.e. system suitability) in proteomic workflows. To this end, several freely available tools have been introduced that monitor a number of peptide identification (ID) and/or peptide ID free metrics. Peptide ID metrics include numbers of proteins, peptides, or peptide spectral matches identified from a complex mixture. Peptide ID free metrics include retention time reproducibility, full width half maximum, ion injection times, and integrated peptide intensities. The main driving force in the development of these tools is to monitor both intra- and interexperiment performance variability and to identify sources of variation. The purpose of this review is to summarize and evaluate these tools based on versatility, automation, vendor neutrality, metrics monitored, and visualization capabilities. In addition, the implementation of a robust system suitability workflow is discussed in terms of metrics, type of standard, and frequency of evaluation along with the obstacles to overcome prior to incorporating a more proactive approach to overall quality control in liquid chromatography coupled to tandem mass spectrometry based proteomic workflows.