Contribution of supercritical fluid chromatography to serially coupling columns for chiral and achiral separations

Abstract

Serially-coupled columns are a useful alternative to achieve a desired chromatographic separation when a single column has failed. Compared to gas chromatography which is limited to volatile compounds, and liquid chromatography's limitation by the high pressure drop over serial columns, supercritical fluid chromatography (SFC) appears to be an interesting alternative method. The SFC mobile phase, containing an elevated percentage of carbon dioxide, has a low viscosity and a high diffusivity compared to the liquid mobile phases. Consequently, higher flow rates can be implemented which reduce the time of analysis and allow the use of several columns in series to increase separation efficiency without any impact on pressure. The unique mobile phase used in SFC, composed of carbon dioxide and a small amount of co-solvent, also facilitates the coupling of complementary stationary phases which increases the range of possible selectivity. Thus, improved efficiency and selectivity together offer the promise of high-resolution separations. On the other hand, because the fluid is compressible, increasing the column length will change the mobile phase density, increasing its eluotropic strength and decreasing the retention time. While this feature can be seen as an advantage, it is also the major challenge of serially-coupling columns as it can be difficult to predict the outcome of the separation. This review depicts the historical milestones of the contribution of SFC to serially-coupled, packed columns, for both achiral and chiral separations. It covers a period from the 1960's to date and describes the evolutions of the concept and how the main drawbacks can be tackled. A section is devoted to applications, illustrating the potential of this concept to successfully achieve the most challenging separations.