“…In LC-MS analysis, the combination of hydrophilic interaction liquid chromatography (HILIC, e.g., bare silica, amide, diol, amido, zwitterionic columns) and reversed-phase liquid chromatography (RPLC, e.g., C18, C8, C30 columns) methods is one the most comprehensive strategies for untargeted metabolomics, providing a broad metabolite coverage [ 95 , 96 , 97 ]. Currently, C18 columns with sub-2-μm particle size are often used for untargeted metabolomics and lipidomics as a stand-alone technique, and rarely combined with HILIC [ 22 , 23 , 31 , 36 , 48 , 51 , 83 , 85 , 87 , 88 , 98 ]. Furthermore, the complementarity of HILIC to RPLC methods is a highly powerful strategy for polar metabolites that should not be overlooked, especially when a multiplatform strategy is not employed [ 97 , 99 ].…”