基于石墨烯/磁纳米颗粒电化学免疫传感器的二氢吡啶类药物手性拆分及定量检测的研究

手性药物的拆分是其理化性质、药理活性及药物动力学研究的前提。但如何建立一种快速、简便、灵敏、可靠的手性药物拆分方法仍然是研究的难点。免疫分析方法具有灵敏度高、特异性强、快速、简便等优点，若能将免疫分析应用到手性药物的拆分中将大大提高其拆分效率。.本项目拟采用化学合成方法制备二氢吡啶类药物理想的半抗原及完全抗原，并制备其通用型具有手性识别能力的抗体。使用计算机辅助设计技术探究手性抗原抗体识别机理。借助石墨烯包裹的磁纳米颗粒作为固定相。同时，制备磁性电极，通过简单易行的磁力作用将偶联有抗体的石墨烯包裹磁纳米颗粒复合物与磁性电极组成非标记的电化学免疫传感器，通过抗体的手性识别能力来轻松地拆分手性药物。另外，通过抗原抗体结合前后电信号的变化来实现对映体的定量检测。该方法将实现二氢吡啶类手性药物的快速、简便、灵敏拆分及定量测定，并揭示手性抗原抗体识别机理，具有良好的研究意义和应用价值。

One of the outstanding prerequisites of studying on the physicochemical property, pharmacological activity and pharmacokinetics of enantiomers is enantiomeric separation. How to develop a rapid, convenient, sensitive and reliable separation method for chiral drugs is still the difficulty of study. Immunoassay has the advantages of high sensitivity, excellent specificity, rapidness and ease, which will exhibits potential applications in enantiomeric separating effectively. .In this project, the ideal hapten and immunogen of dihydropyridines will be designed and synthesized firstly. Based on that, polyclonal and monoclonal antibodies with group specificity to enantiomers of dihydropyridines will be produced. The recognition mechanism of the antibody to chiral dihydropyridines will be studied by computer aided drug design. Graphene, magnetic nanoparitcles and magnetic electrodes will be prepared respectively and the graphene coated magnetic nanoparticles will be used as the stationary phase where the antibody will be coated further. An easy and label-free electrochemical sensing platform will be developed based on the magnetic loading of graphene coated magnetic nanoparticles composite on electrodes. The enantiomers of dihydropyridines could be easily separated by the chiral recognition of antibody located at the sensor. Simultaneously, quantification of dihydropyridines enantiomers could be achieved by cyclic voltammetry. The proposed method will greatly contribute for rapid, convenient, sensitive and reliable separating and quantifying enantiomers of dihydropyridines which exhibit great significance and remarkable application prospect.