With emerging instrument technologies, such as ultra-high pressure liquid chromatographs and high resolution mass spectrometers, there has been a surge of interest in untargeted analysis of complex materials of biological, industrial, and environmental origin. While these techniques mature, there are few tools available to determine the comparability of untargeted analytical results between laboratories. For this purpose, we have investigated the use of a solution that contains chemically-informative compounds as a potential reference material for harmonization, as well as to evaluate the performance of an untargeted instrumental method over time. The material could be applied to untargeted techniques such as metabolomics, process monitoring, and environmental non-targeted screening. The prototype solution evaluates chromatographic and mass spectrometric parameters of a method, including (but not limited to) silanol activity of the chromatographic column, mobile phase pH, adduct formation, ionization efficiency, and fragmentation efficiency. A wide range of compounds were tested, such as polymeric compounds, pharmaceutical acids/bases, and chelating agents, for their ability to describe LC-HRMS method performance parameters. For example, saturated fatty acid methyl esters provide a pH-independent tool for evaluating the retention of hydrophobic homologues of reversed-phase columns, although variability does arise from columns of similar silanol functionality but different manufacturers. Due to variations in end-capping, polar-embedding, and ligand density of the stationary phase of the column, the selectivity of the columns can change and specific compounds, such as haloperidol, were used to evaluate the significance of this selectivity change. With the test solutions, multiple LC columns, LC-MS systems and various method modifications (e.g., mobile phase buffer salts and pH, and ESI source conditions) were used to examine the variability of the signal response for the compounds and how the response is altered with the method/instrument modifications. Presented will be the results of preliminary compound testing and demonstration of prototype solutions using different separation protocols, ionization parameters, and instrument manufacturers.

Development of a test mixture for untargeted HRMS method harmonization

254th National Meeting (2017)

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