A general obstacle with polyphenols that complicates feature annotation is that they are a chemical class that contains a vast number of positional, constitutional and stereoisomers, which is complexified if human biotransformation products are included. For example, for many features in Table it is difficult to tell which position the conjugation occurs as MS 2 spectra are extremely similar. Additionally, different unique features were matched with the same analyte, e.g. two features with retention times 4.54 and 5.11 min both had a spectral library match with either m-, p-, or o-cresol (Table ). Chromatographic separation of isomers is a challenging endeavor, as seen here where apigenin and genistein both have the same monoisotopic mass and their retention times are 8.28 and 8.29, respectively (Table ). Therefore, they will have the same chromatographic peak and their MS 2 spectra will be acquired together. This is not an issue in targeted workflows as these two compounds will have distinct quantifier/qualifier ions. This may be overcome in untargeted workflows by adding ion mobility as a complementary dimension to HRMS to separate co-eluting compounds and increase the confidence of structural elucidation .