It is reported in literature that depending on the analytes and instruments chosen, HRMS may perform better or worse than LRMS . In one study comparing HRMS and LRMS for a multi-class xenobiotic method , the authors concluded that LRMS would be more suited and the preferred platform for quantification of such compounds. Different from those small molecules, polyphenols are a more homogenous class, present in higher concentrations and with overall better ionization efficiency due to stabilization of proton loss by their aromatic rings and lower background noise in negative ESI mode . Therefore, as shown here, the sensitivity of HRMS approaches that of LRMS for most polyphenols, with the additional potential of a broader screening that includes their secondary metabolites (e.g. sulfates and glucuronides).