Modification of a commercial chiral stationary phase influences on enantiomer separations using simulated moving bed chromatography.
Chromatographic enantiomer separations using high-performance chromatography and the simulated moving bed (SMB) principle have become a practically useful method for obtaining optical isomers. The carbamate derivatives of amylose coated onto silica particles are very effective chiral stationary phases (CSPs). Several lots of Chiralpak AS, and its successor, Chiralpak AS-V, were compared by laser diffraction, microscopic imaging and pulse injections with increasing amounts of various racemates in order to determine the loading capacity and the competitive adsorption isotherms. Software simulations allowed to assess the possible effects due to the observed variations between the CSPs on the performance of a pilot SMB unit. The obtained results were verified by two multi-kilogram separations performed under current good manufacturing principles (cGMP) guidelines employing the two CSPs. The results of the two production runs are discussed in the light of the recently introduced "triangle theory" which allows to account for the overload conditions prevailing under preparative chromatographic conditions and to predict optimal operating conditions. Under optimized conditions the enantiomer separation of 1.4 kg racemate/kg stationary phase per day with purities >99.6% for the target enantiomer have been achieved.
Huthmann
E
E
CarboGen Laboratories (Aarau)AG, Switzerland.
Juza
M
M
D000327:Adsorption; D002853:Chromatography, Liquid / Q000295:instrumentation* / Q000379:methods; D010316:Particle Size; D013237:Stereoisomerism; D013816:Thermodynamics