Most current reports, investigating the potential of mixed-mode phases in HPLC, describe stationary phases containing both hydrophobic and anionic groups [1, 2], as well as both hydrophobic and cationic groups [3].These stationary phases showed ion-exchange interaction with analytes, in addition to reversed-phase partitioning interaction.They have been explored in the separation of biological molecules such as amino acids, nucleic acids, peptides and proteins [3].In this work, a stationary phase with a quaternary ammonium embedded group (QA-C13) was developed and first used to selective separation of alkaloids in complex Traditional Chinese Medicine (TCM) based on ion-exclusion interaction.Under acidic condition, both alkaloids and stationary phase have positive charges, and the ion-exclusion interaction between them dominates and makes the alkaloids be eluted near to the dead time, while other compounds still have good retention.