ABSTRACT
Small polar compounds, although representing only a small portion of therapeutic drugs, are often very challenging to pharmaceutical analysis. Lack of suf“cient retention on reversed-phase columns makes it dif“cult to analyze polar compounds by reversed-phase liquid chromatography (RPLC). Hydrophilic interaction chromatography (HILIC) provides a viable alternative to ion-pairing or normal phase methods, which are typically used for the analysis of polar and/or ionizable compounds. Recent reviews on HILIC reveal increasing popularity of HILIC in pharmaceutical analysis of small polar drugs (Hemstrom and Irgum 2006, Dejaegher and Heyden 2010, Jian et al. 2010). The term “hydrophilic interaction chromatography” (HILIC) was “rst coined by Andrew Alpert in 1990 (Alpert 1990); however, similar separation technique had been used for sugar analysis much earlier (Linden and Lawhead 1975, Palmer 1975). Alpert also postulated the retention mechanism for HILIC as hydrophilic partitioning of polar solutes between the organic solvent-rich mobile phase and a water-rich liquid layer immobilized on the surface of polar stationary
17.1 Introduction .................................................................................................. 401 17.2 Polar Stationary Phases for HILIC ...............................................................402 17.3 Selectivity of Various Polar Stationary Phases in HILIC.............................406 17.4 Retentivity of Various Polar Stationary Phases in HILIC ............................ 413 17.5 Factors Affecting Retention and Selectivity in HILIC ................................. 415 17.6 Separation of Positional Isomers in HILIC .................................................. 422 17.7 Conclusions ................................................................................................... 423 Acknowledgment ...................................................................................................424 References ..............................................................................................................424
