The advantages of ESI‐MS detection in conjunction with HILIC mode separations: Fundamentals and applications

The analysis of highly hydrophilic, ionic, and polar compounds has been performed by HILIC‐ESI‐MS for the last few years. The use of low aqueous/high polar organic solvent content in HILIC separation mobile phase is almost ideal for ESI‐MS detection in many cases, resulting in increased sensitivity. Although the addition of modifiers such as acids or salts is necessary in some circumstances for a good separation, the optimum concentrations used are still highly amenable for ESI‐MS analysis, showing few deleterious effects. In this review, the mechanism of HILIC separation and ESI ion generation will be briefly discussed, followed by a summary of method development and applications in several fields of research including pharmaceutical, biomolecular, food, metabolic, and environmental analysis.