(761f) Method Development in the Separation of an Enantiomer with Supercritical Fluid Chromatography

Supercritical fluid chromatography (SFC), which uses sub/supercritical carbon-dioxide as the principal solvent in chromatographic operations, is steadily replacing HPLC in various industrial separations, especially in the separation of enantiomers. The main advantage of SFC compared to HPLC is the increment in productivity by several times. Additionally, the usage of carbon-dioxide, a carbon neutral green solvent, increases the sustainability of the chromatographic processes significantly. The main problems in a wider application of SFC are its operational complexity and lack of physical understanding in designing more competitive industrial processes. This hinders the industrial practitioners from developing or transferring optimized operational methods for a particular separation.

The separation performance in SFC strongly depends on the solvent density, and to a lesser extent, on the temperature. This indicates that the effects of the operating conditions on chromatographic performances can be understood more clearly by following the changes in both the density and the temperature, rather than analyzing the operating variables i.e. the pressure and the temperature [1,2]. In other words, SFC operations can be more clearly analyzed based on the iso-density or isopycnic plots, drawn on the pressure-temperature plane, compared to an analysis based on the isobars and the isotherms.

The talk will demonstrate that guided by the solvent isopycnic plots on the pressure-temperature plane, one can develop effective separation methods quickly, without the help of detailed simulation studies. The demonstration will be based on the separation problem of the enantiomers of Naproxen, a nonsteroidal anti-inflammatory drug (NSAID). First the variation of the separation factors of the two enantiomers will be investigated as a function of the density and the temperature of the mobile phase. The optimum separation method in terms of the best combination of high yield and high productivity will then be selected based on this data.

1. A. Tarafder, G. Guiochon: Use of isopycnic plots in designing operations of supercritical fluid chromatography: I. The critical role of density in determining the characteristics of the mobile phase in supercritical fluid chromatography, Journal of Chromatography A, 1218 (2011) 4569– 4575.
2.  A. Tarafder, G. Guiochon: Use of isopycnic plots in designing operations of supercritical fluid chromatography: II. The isopycnic plots and the selection of the operating pressure–temperature zone in supercritical fluid chromatography, Journal of Chromatography A, 1218 (2011) 4576– 4585.