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Based on this background, this article reviews the derivatization-based sample-multiplexing strategy, especially the characteristics and applications of the derivatization reagents, for the LC/MS/MS quantification of metabolites. This strategy has been used for the relative and absolute quantification of a variety of metabolites, and expansion of the coverage of metabolites.A novel reversed-phase/hydrophilic interaction/ion-exchange (RPLC/HILIC/IEC) and chiral recognition mixed-mode stationary phase material was synthesized using 3-n-octad