Application Of Molecular Imprinting And Related Technologies On Chiral Separation Of Nateglinide

Molecular Imprinting Technology (MIT) has been proved to be an effective tool for chiral separation, solid-phase extraction, sensors, etc. In this thesis, molecularly imprinted polymers (MIP) based on nateglinide, an orally drug of active secretagogue, were prepared and have been used as HPLC chiral stationary phases (CSP). The chromatographic performance, absorption and thermodynamic characteristics of chiral separation on MIP-CSP were investigated. There are five chapters in this thesis.In Chapter I, the principle of MIT, polymerization methods, application of this technique and its future developments were introduced. And the applications of HPLC on chiral separation and HPLC-ELSD technology were also described.In Chapter II, bulk, rod and microsphere MIP were prepared by different approaches. Experiments showed that all of those MIP had wonderful enantio-selectivities on nateglinide and its L-enantiomer even their chromatographic performances were different.In Chapter III, the characteristics of adsorption and thermodynamics of nateglinide-MIP were investigated. The adsorption isotherms of neteglinide and L-enantiomer were studied by static method. Schatchard analysis indicated that two classes of binding site were present in the imprinted polymers.In Chapter IV, separation of neteglinide and its cw-isomer on nateglinide-MIP was performed and the recognition mechanism was deduced. Meanwhile, the analog compound separations on MIP were also introduced.In Chapter V, cholic acid in An-Gong Niuhuang capsules and stachyose in Stachys sieboldii Miq. were determined by HPLC-ELSD. It was expected that the MIP could be used more widely by using this HPLC-ELSD method.