Separation And Preparation Of Chiral Drug Ornidazole Enantiomers

The chiral drugs study is one of hot issues in the field of chemicals at home and abroad. The enantiomers of chiral drug may have different effects or even the opposite effects. So, it is an important issue that how to prepare a single enantiomer drugs. The advantages of liquid-liquid extraction are simple equipment, industrialization, low production cost, continuous production process, and wide application. Therefore, liquid-liquid extraction is playing an important role on preparation a single enantiomer drugs. In the extraction, biphasic recognition chiral extraction will have a bright business future. In this paper, antibiotic ornidazole (ONZ) enantiomers were separated by a new chiral separation technique-biphasic recognition chiral extraction. The main contents can be summarized as follows:1The separation of ornidazole enantiomers was performed by HPLC. The factor of the organic solute content, pH value, the velocity and temperature on separation was investigated. Additionally, the daicel chiralcel OD-H column was applied with the mobile phase consisting of N-hexane-isopropyl alcohol-acetic acid (95:5:0.1), injection volume was20μL, column temperature was5℃and flow rate was1.0mL/min. The method can be used for separating the enantiomers of ornidazole.2Separation extraction of ornidazole enantiomers:the influence of the kind organic solute、the kind and concentration of ((3-CD derivatives and tartrate derivatives) pH value and temperature on extraction performance was investigated. The experimental results indicate that biphasic recognition chiral extraction is of strong chiral separation ability. β-CD derivatives have higher recognition ability for S-ornidazole isomer than that for R-ornidazole isomer, and tartrate derivatives have the same recognition ability for them. Meanwhile, the temperature and pH value have great effects on chiral separation ability. We can see that the dual phase identification extraction system have good separation and it provides a theoretical basis for the preparation of single ornidazole enantiomer. 3The inclusion complex formation of ornidazole with β-cyclodextrin derivatives and bovine serum albumin (BSA) were studied by using ultraviolet spectroscopy. Meanwhile, thermodynamic parameters for the binding of HP-β-cyclodextrin or BSA and ornidazole were investigated. The effects of alcohol and ionic strength on inclusion behavior had been further investigated. Stable inclusion complex in solid state were characterized by IR spectra. The experiment can well explain the relationship of chiral extractant and ornidazole. And furthermore, it provides a theoretical basis for the choice of the chiral recognition extractant.