ERLIC

In 2008, Alpert coined the term, ERLIC [3] (Electrostatic Repulsion Hydrophilic Interaction Chromatography), for HILIC separations where an ionic column surface chemistry is used to repel a common ionic polar group on an analyte or within a set of analytes, to facilitate separation by the remaining polar groups. This allows one to minimize the influence of the common, ionic group within the set of molecules; or to reduce the degree of retention from these more polar functional groups, enabling isocratic separations.

Choice of pH

With surface chemistries that are weakly ionic, the choice of pH can affect the ionic nature of the column chemistry. Properly adjusted, the pH can be set to reduce the selectivity toward functional groups with the same charge as the column, or enhance it for oppositely charged functional groups. Similarly, the choice of pH affects the polarity of the solutes. However, for column surface chemistries that are strongly ionic, and thus resistant to pH values in the mid-range of the pH scale (pH 3.5-8.5), these separations will be reflective of the polarity of the analytes alone, and thus might be easier to understand when doing methods development.

Cation exchange

For example, one could use a cation exchange surface (negatively charged) chemistry for ERLIC separations to reduce the influence of the anionic (negatively charged) groups (phosphates of nucleotides or of phosphonyl antibiotic mixtures, or sialic acid groups of modified carbohydrates) to allow discrimination based on the basic and/or neutral functional groups of these molecules. Alternatively, one could use a pH 9.2 mobile phase on a polymeric, zwitterionic, betain-sulphonate surface to enhance the influence of its sulphonic acid functional group over the, now diminished, quaternary amine of this surface chemistry to separate the phosphonyl antibiotic mixtures. Commensurate with this, these analytes will show a reduced retention on the column chemistry and will elute earlier and in higher amounts of organic solvent than if a neutral polar HILIC surface were used. This then increases their detection sensitivity by mass spectrometry.

 Anion exchange

By analogy, one could use an anion exchange column surface (positively charged) chemistry to reduce the influence of cationic (positively charged) functional groups on a set of analytes, as when selectively isolating phosphorylated peptide molecules. Use of a pH between 1 and 2 pH units will reduce the polarity of two of the three ionizable oxygens of the phosphate group, and thus will allow easy desorption from the (oppositely charged) surface chemistry. It will also reduce the influence of negatively charged carboxyls in the analytes, since they will be protonated at this low a pH value, and thus contribute less overall polarity to the molecule. The common, positively charged amino group will be repelled from the column surface chemistry and thus these conditions will enhance the role of the phosphate's polarity (as well as other neutral polar groups) in the separation.

 Alpert, Andrew J. (January 2008). "Electrostatic Repulsion Hydrophilic Interaction Chromatography for Isocratic Separation of Charged Solutes and Selective Isolation of Phosphopeptides". Anal. Chem. 80: 62–76. doi:10.1021/ac070997