Simulated moving bed (SMB) chromatography is a powerful tool for chiral separation, because of its many advantages with respect to discontinuous batch chromatography, namely higher product purity, less solvent consumption, and higher productivity per unit stationary phase. Newly developed cyclic operating schemes and column configurations are pushing the trend toward the use of units with fewer columns and more economical set-ups.

Despite the lower productivity and higher solvent consumption of batch processes, they are advantageous in other respects, such as in their simplicity (less design effort is necessary and the scale-up is easier), flexibility (changes in conditions can be easily handled), and versatility (multi- and center-cut separations from multi-component mixtures are easy to implement).

Somewhere in between, and in an attempt to work with the best of "two worlds", we have developed a compact, two-column open-loop SMB process for enantiomeric separation, which is particularly effective when the resolution is limited.

On the other hand, product quality control is mandatory for chiral separations, which requires robust on-line monitoring of the individual enantiomer concentrations. We have successfully implemented an on-line monitoring system, comprising an HPLC set-up with two UV detectors, to measure the individual enantiomeric concentration profiles in the SMB unit. Our monitoring scheme does not use a polarimeter.

The chiral separation considered in this work is the separation of Reboxetine enantiomers on Chiralpak AD, using a mixture of Hexane-Ethanol-DEA as solvent. This system is one in which there is clearly a lack of resolution between the two components. It is thus difficult to obtain both products with high purity and yield by HPLC for the chosen chromatographic conditions. Reboxetine, (RS)-2-[(RS)-Ą-(2-ethoxyphenoxy)benzyl]-morpholine is an antidepressive NRI drug. Only the (R,R)-, (S,S)-pair is present as a racemic mixture in the active principle and the commercial formulations. Recent studies support the hypothesis that the (S,S)-enantiomer is a more potent inhibitor than the (R,R)- and that it is responsible for the vasomotor and cardiac side effects of Reboxetine.