Effect of nature of electrolytes on retention and selectivity in hydrophilic interaction liquid chromatography

This work investigates the selectivity and retention changes on four classes of HILIC columns upon addition of 1-20 mM electrolyte. The effect of four electrolytes (Na⁺Cl^-, Na⁺ClO₄^-, Na⁺PF₆^-, and Na⁺CF₃CO₂^-) were tested on neutral, cationic, anionic, and zwitterionic analytes under HILIC conditions (70-90% ACN). These electrolytes alter the retention and selectivity on silica, zwitterionic and diol columns through ion exchange and ionic screening mechanisms. Neutral analytes were unaffected by addition of 1-20 mM electrolyte, indicating minimal change to the retentivity of the water layer. Cationic and anionic analytes increase and decrease in retention, respectively (Na⁺PF₆^- ≈ Na⁺ClO₄^- > Na⁺CF₃CO₂^- > Na⁺Cl^-). Chaotropic electrolytes accumulate at the mobile phase/water layer interface, enhancing the ion exchange and ionic screening effects of the mobile phase electrolyte. Altering the buffer cation (Li⁺, Na⁺, K⁺) caused small but statistically significant changes in retention.