逆相系糖誘導体カラムにおける光学異性体分離機構の解明

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A reversed-phase HPLC method was investigated for the separation of enantiomers, the newly synthesized potential medicinal substance and corresponding optical impurity, employing polysaccharidebased chiral stationary phases (CHIRALCEL OD-RH and CHIRALPAK AD-RH). On the CHIRALCEL OD-RH column, chiral recognition was completely enthalpy-driven with a negative en tropic contribution. The cavity formation effect was the major factor governing the solute distribution between the mobile and stationary phases for acetonitrile-rich mobile phase, while the effect of solvation due to acid-base equilibrium became significant in highly aqueous mobile phase. On the CHIRALPAK AD-RH column, the enantio-selectivity was exclusively driven by enthalpy above about 20℃, whereas below about 20℃ enantio-separation was achieved by the combination of enthalpy and entropy. A conformationed change in the stationary phase of the CHIRALPAK AD-RH column was observed at about 20℃. Enthalpy-entropy compensation concerning enantio-separation on both columns indicated that enthalpic gain/loss was substantially cancelled out by the entropic loss/gain. The CHIRALPAK AD-RH column was used for the determination of enantiomers (optical impurity). A low-level quantification (0.05%) of the minor enantiomer was achieved. The analytical procedure was validated and successfully applied to the detection of the optical impurity in potential medicinal substance.
2004-10-05