High Performance Liquid Chromatographic Separation Of Chiral Enantiomers Using Chiral Mobile Phase Additive

The chiral enationmers possess similar physico-chemical properties, but they have different properties in bioactivity, toxicity and mechanism of metabolizability. In general, only one of enationmers is biologically active or possess pharmacological relevance, the other enantiomer effect is very small, even have no efficacy or have the opposite effect. Although the individual enantiomers of chiral drug own great different pharmacological and toxicological properties, a lot of chiral drugs are sold in the form of racemates currently, this cause the researcher’s recognition. Therefore, rapid and sensitive methods for the resolution and quantification of the individual optically pure enantiomers are of great importance, especially at the separation of chiral drugs. The United States food and drug administration announced formally about sales for chiral drug development on the basis of the documents, made clear that the new listing of the chiral drugs must indicate the enantiomeric purity, this improves the requirements of high optical purity of chiral drugs in the pharmaceutical industry. The trend of pharmaceutical industry toward commercializing chiral drugs as pure enantiomers enhances the need of efficient processes for the separation of racemates. Among all the chiral separation techniques, high performance liquid chromatography has proven to be the most convenient, reproducible and widely applicable method. In this paper the separation of terfenadine enantiomers and zopiclone enantiomers has been investigated by means of chiral mobile phase additive respectively.In part Ⅰ, a review on chiral resolution by high performance liquid chromatography is presented. Basically, different approaches for the liquid chromatography resolution of enantiomers and the types of chiral selector are introduced. This review also deals with the development and present state of chiral selectors.In part Ⅱ, the experimental data processing method of high performance liquid chromatography and the basic theory of chiral separation by high performance liquid chromatography are described.In part Ⅲ, The enantiomeric resolution of terfenadine was studied by using reversed-phase high performance liquid chromatography with β-cyclodextrin (β-CD) as chiral mobile additive. Through the analysis of various experimental factors, the best chromatographic conditions of terfenadine enantiomers have been obtained. The results showed that nearly baseline separation of terfenadine enantiomers were obtained as the optimized mobile phase was 15 mmol/L β-cyclodextrin containing 20 mmol/L phosphate buffer:methanol (60:40, V/V) with the flow rate set at 0.8 mL/min, at pH 6.0, the temperature of 40℃, the detection wavelength was set at 210 nm and the injection volume was 20 μL, the separation of terfenadine enantiomers was 1.46. Therefore, this can provides a new method for the further study of terfenadine enantiomers.In part Ⅳ, The enantiomeric resolution of zopiclone was studied by using reversed-phase high performance liquid chromatography with β-cyclodextrin (β-CD) as chiral mobile additive. Through the analysis of various experimental factors, the best chromatographic conditions of zopiclone enantiomers have been obtained. The results showed that baseline separation of zopiclone enantiomers were obtained as the optimized mobile phase was 15 mmol/L β-cyclodextrin containing 20 mmol/L phosphate buffer:methanol (85:15, V/V) with the flow rate set at 0.8 mL/min, at pH 5.5, the temperature of 35℃, the detection wavelength was set at 305 nm and the injection volume was 20 μL, the separation of zopiclone enantiomers was 1.62. Therefore, this can provides a new method for the further study of zopiclone enantiomers.