On-line enantiomeric analysis using high-performance liquid chromatography in chiral separation by simulated moving bed

An automated on-line enantiomeric analysis system comprising an analytical HPLC set-up with two UV detectors sharing the same light source has been employed to monitor the internal composition profile in chiral simulated moving bed chromatography. This monitoring scheme does not use a polarimeter. Using a sampling interface placed between two SMB columns, effluent samples are directed onto a high-efficiency analytical column at a sampling rate faster than the overall dynamics of the preparative unit to achieve on-line enantiomeric analysis of the composition profile. The other UV detector is placed in the SMB loop before the fraction collector to provide instantaneous measurement of the total enantiomeric concentration. The feasibility and effectiveness of the on-line enantiomeric monitoring scheme were assessed experimentally on the separation of Tr?ger's base racemate, using Chiralpak AD as stationary phase and methanol as eluent. It was found that robust monitoring of the concentration profiles of the individual enantiomers is best achieved when the enantiomeric purity obtained from the peak areas of the on-line enantiomer analysis chromatograms is combined with the on-line UV measurement of total enantiomeric concentration. The accuracy and robustness of the proposed on-line enantiomeric monitoring system open up promising perspectives for process control and dynamic optimization of the SMB.