Preparation And Modification Of Silica Microspheres With Different Structures And Their Application In High Performance Liquid Chromatography

With the rapid development of the medical profession,people have a higher demand for single enantiomers,so the separation of chiral drugs is a hot topic at this stage.Liquid chromatography has the advantages of high separation efficiency,fast separation speed,mature technology,simple operation,good stability,etc.,so this method has become the most common means to achieve enantiomeric separation.In this paper,using diazo resin as the coupling agent,the mono-derivatized p-methylphenylurea?-cyclodextrin and the hexamethylene diureido bridged?-cyclodextrin were modified on the surface of the mesoporous silica microspheres,two?-cyclodextrin chiral stationary phases were prepared,and the separation effects under different separation systems were explored.This article mainly includes the following four parts of work:1.On the basis of the sol-gel method,2?m mesoporous silica microspheres were prepared by the template method,and the particle size,pore diameter and mechanical strength of the microspheres were characterized,and the factors affecting the particle size of mesoporous silica microspheres were studied.2.2?m non-porous and 2?m core-shell silica microspheres were prepared by the improved St(?)ber method,three kinds of silica microspheres were modified with octadecyltrichlorosilane,and three kinds of C₁₈modified silica microspheres were prepared.It was applied to high performance liquid chromatography to compare the separation of benzene homologues of three kinds of C₁₈modified silica microspheres with the same particle size and different structures.3.Using diazoresin as the coupling agent,p-methylphenylurea?-cyclodextrin was modified on the surface of 2?m mesoporous silica microspheres to prepare p-methylphenylurea?-cyclodextrin chiral stationary phase.This chiral stationary phase separates chlorpheniramine maleate,2-phenylcyclohexanone,promethazine and metoprolol tartrate.The chromatographic conditions were optimized,and the effects of mobile phase ratio,flow rate and TEAA buffer on the separation effect were studied.This mono-derived ureido cyclodextrin chiral stationary phase has clear structure,stable properties and good repeatability,as a coupling agent,diazoresin has the advantages of non-toxic and environmental protection,and it is of great significance to replace silane coupling agent in the separation of chiral drugs.4.The hexamethylene diureido-bridged?-cyclodextrin was modified on the surface of2?m mesoporous silica microspheres by diazoresin to prepare the chiral immobilization of the hexamethylene diureido-bridged?-cyclodextrin phase.This chiral stationary phase separates ketoprofen,2-phenylcyclohexanone,promethazine,ibuprofen,chlorpheniramine maleate,trans-stilbene oxide and flavonoids under different separation modes.In addition,the influence of the type of mobile phase and the ratio of the mobile phase on the separation effect was studied.Bridged cyclodextrin has a synergistic inclusion effect,and the separation effect of chiral drugs is greatly improved,the problem of low separation efficiency and poor peak shape of the chiral stationary phase modified by diazoresin is effectively improved.