Packed column supercritical fluid chromatography of hydrophilic analytes via water-rich modifiers

The use of additives to dramatically extend the range of solute polarity amenable to CO2 based supercritical fluid chromatography (pcSFC) was predicted over 20 years ago. At that time additives were predicted to have multiple functions such as enhancement of mobile phase solvating power, ion suppression, and ion pairing. The adsorption of mobile phase components on the stationary phase causing a modification of its surface was predicted, but the implications for separations were not defined. Reports published in the late 1980s showed that while water could not function as a primary modifier due to it poor solubility in carbon dioxide, its use as an additive was more promising. The past decade has seen very little published work concerning water and pcSFC. Now reports are beginning to appear that demonstrate enhanced selectivity with water, and application of the technology to polypeptide salts, drug molecules, and nucleobases. This review attempts to bridge the past with the present. As evidenced by the studies described in this review, water may offer much potential as an additive in that it could (a) enhance the solvating power of the mobile phase, (b) introduce HILIC-like analyte partitioning, (c) simplify preparative purifications, and (d) offer a more mass spectrometrically compatible interface.

► Water as a neutral additive has been shown to enhance pcSFC selectivity.
► Water enhances solvation of polar analytes and the stationary phase.
► After 20 years, water is finding new applications in pcSFC.