Analytical supercritical fluid chromatography using fully automated column and modifier selection valves for the rapid development of chiral separations

Automated analytical supercritical fluid chromatography is used to separate enantiomers of pharmaceutical compounds in the drug discovery laboratory. Modification of a commercial instrument to incorporate a six-way column selection valve, multiple chiral columns based on derivatized cellulose or amylose, and a four-way modifier selection valve provides a powerful combination for the rapid development of chiral separations. A wide set of columns and conditions can be tested sequentially, including unattended operation overnight. This paper shows that similar racemic compounds, even those from the same molecular class, are separated using different column and modifier combinations. Therefore, the use of program-controlled column and modifier selectors has great advantages. Using the fully automated system, the optimal chiral separation of several compounds can be obtained unattended within 24 h. (C) 1998 Published by Elsevier Science B.V. All rights reserved.