Design and evaluation of a dicationic ionic liquid-embedded C18 stationary phase for mixed-mode chromatography

A novel mixed-mode stationary phase, Sil-DIL-C18, was successfully developed by covalently embedding a dicationic dipyridinium ionic liquid within the C18 chains grafted to the silica. The chromatographic retention was systematically evaluated under varying mobile-phase composition, salt concentration, and pH. Compared with conventional single-mode Extend-C18 and HILIC Plus columns, Sil-DIL-C18 exhibited markedly superior resolution of both hydrophobic solutes (alkylbenzenes and PAHs) and polar/ionizable compounds (nucleosides, sulfonamides, alkaloids, organic acids, and antipyretic analgesics). This superior versatility was achieved by simply tuning the mobile-phase composition to activate reversed-phase, hydrophilic, or ion-exchange mechanisms on the same column. The embedded dipyridinium dicationic moieties not only conferred good compatibility with highly aqueous mobile phases but also improved peak symmetry for basic analytes, thereby overcoming major limitations of traditional alkyl-bonded phases. Retention mechanisms were quantitatively elucidated using Abraham's solvation parameter model and Tanaka tests, confirming the synergistic contribution of multi-modal interactions. The new column also demonstrated excellent retention repeatability. Owing to these advantages, Sil-DIL-C18 was successfully applied to the determination of acetaminophen in commercial Tylenol tablets.