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The present work intends to investigate how mobile phase composition influences the adsorption behavior of ketoprofen enantiomers (a nonsteroidal anti-inflammatory drug) on an amylose-based chiral stationary phase (Chiralpak AD). Three mobile phase compositions were studied: the usual 20% ethanol/80% n-hexane mixture and two pure mobile phases; methanol and ethanol. Pulse and breakthrough experiments under preparative conditions were carried out in order to measure and test adsorption isotherms. The results obtained show that, for preparative separations, pure ethanol is a better mobile phase than the usual 20% ethanol/80% n-hexane mixture: it allows higher solubility of the racemate, lower retention times, and also a higher selectivity at high enantiomer concentrations. These are aspects of crucial importance when the final goal is to achieve high productivity preparative separations, as it is shown for the simulated moving bed (SMB) operation.