Thick Liquid Membrane And Foam Fractionation Technology Split Drug Enantiomers And Its Mechanism

In this paper,the establishment of analytical methods about separation of chiral drugs and their thermodynamic properties of chiral mobile phase addition(CMPA) method were investigated.Additionally mandelic acid enantiomers and methionine enantiomers were separated by the techniques of bulk liquid membrane and foam fractionation respectively,while the influencing factors of separation and the separation mechanism was also discussed.(1) Establishment of analytical methods.The chiral analysis methods were established for mandelic acid and ofloxacin by CMPA and methionine by chiral stationary phase,respectively.Furthermore,the optimal conditions for enantiomeric analysis was confirmed.(2) Investigation of the thermodynamic properties of resolution of ofloxacin enantiomers by CMPA.The effect of temperature(293～313K) on chromatographic separation of ofloxacin over a C18 column was investigated with L-phenylalanine-CuSO₄ aqueous solution and methanol as the chiral ligand mobile phase.Higher column temperature was found to be disadvantageous to the enantiomer separation for the retention time, resolution and selectivity of the chiral separation were decreased with the increase of temperature.Moreover and very importantly,the enantiomeric separation is a enthalpy controlled process in the examined temperature range by calculation of thermodynamic functions(△H°,△_S,R△H°,△_S,R△S°).(3) Resolution of mandelic acid enantiomers by the technique of bulk liquid membrane.A new method of bulk liquid membrane using complex of D2EHPA and L-(-)-DBTA was developed for the resolution of racemic mandelic acid.The influences of time,the concentration ratio of MA,D2EHPA and L-(-)-DBTA,rotated speed and temperature on chiral separation were studied and optimized.The biggest separation factor (α)2.74 and the enantiometric excess value(ee%) 46.47%were obtained when the separation time was 4 hour,the concentration ratio of MA, D2EHPA and L-(-)-DBTA was 0.05:0.2:0.3,the rotated speed was 400r/min and the temperature was 35℃.(4) Resolution of methionine enantiomers by the technique of foam fractionation.Mandelic acid and methionine enantiomers were separated using different chiral collectors by the technique of foam fractionation. The species of chiral collectors,the concentration ratio of collectors and chiral enantiomers,reflux equilibriation time,gas flow rate,packing height and pH of buffer on resolution performances were investigated, respectively.The effects of different factors on resolution of methionine enantiomers were studied by Orthogonal experiment.After variance analysis,it was found that the influences of reflux equilibriation time and the concentration ratio of sample solution were greater in resolution of methionine enantiomers by the technique of foam fractionation.