tSince the ultimate goal of untargeted metabolomics is the analysis of the broadest possible range ofmetabolites, some new metrics have to be used by researchers to evaluate and select different analyticalstrategies when multi-platform analyses are considered. In this context, we aimed at developing a scoringapproach allowing to compare the performance of different LC–MS conditions for metabolomics studies.By taking into account both chromatographic and MS attributes of the analytes' peaks (i.e. retention,signal-to-noise ratio, peak intensity and shape), the newly proposed score reflects the potential of a set ofLC–MS operating conditions to provide useful analytical information for a given compound. A chemicallibrary containing 597 metabolites was used as a benchmark to apply this approach on two RPLC andthree HILIC methods hyphenated to high resolution mass spectrometry (HRMS) in positive and negativeionization modes.The scores not only allowed to evaluate each analytical platform, but also to optimize the number ofanalytical methods needed for the analysis of metabolomics samples. As a result, the most informativecombination of three LC methods and ionization modes was found, leading to a coverage of nearly 95%of the detected compounds. It was therefore demonstrated that the overall performance reached withthree selected methods was almost equivalent to the performance reached when five LC–MS conditionswere used.