Experimental determination of chromatographic separation parameters of ketamine enantiomers on MCTA

The use of chromatographic techniques to obtain significant quantities of enantiomerically pure drug intermediates is well established. With respect to batchwise preparative chromatography, simulated moving bed (SMB) units exhibit a number of advantages. In particular, these are due to the continuous nature of the operation and the efficient use of the stationary and mobile phases, which allows the decrease of the dessorbent requirement and the improvement of the productivity per unit time and unit mass of the stationary phase. In this work, a systematic procedure was employed to obtain kinetic and equilibrium data for the chromatographic enantioseparation of ketamine (free base), using the system microcrystalline cellulose triacetate (MCTA) as chiral stationary phase and ethanol as mobile phase. These parameters were required for the design and operation of a preparative SMB adsorption unit. Bed voidage, equilibrium adsorption data, axial dispersion and overall mass transfer coefficients were evaluated by moment analysis. Adsorption isotherms for the enantiomers of ketamine were determined by frontal analysis (FA). The overall mass transfer coefficients were evaluated to be 5.03 and 1.46 min−1 for the S- and R-ketamine, respectively. The isotherms, for both enantiomers, were adjusted satisfactorily to the Langmuir model. The chiral column, in overload conditions, presented the same behavior for both enantiomers, in terms of the variation of retention time with the increase in the load injection.