| Preparative techniques for the separation of drug enantiomers have a great interesting potential. Chiral extraction is a very important method for preparative separation of enantiomers. It has some regularity and a larger application range in contrasting to chemical resolution, fermentation and enzymatic transformation and chromatography. Hollow fiber membrane extraction is a very effective separation technique with great promise. In the thesis, distribution behaviors of ofloxacin, chlorthalidone, mandelic acid and terbutaline enantiomers were examined in the aqueous-organic solvent of a two-phase systerm containing a chiral selector. Influence of pH value, organic solvents and concentrations of chiral selector on the partition coefficients(k) and separation factors( a ) of enantiomers, were investigated. Drug enantiomers were separated by combining chiral extraction and hollow fiber membrane extraction, and mathematical models were established for chiral separation. The main content and results can be summarized as following:1. The enantiomeric resolution of ofloxacin, chlorthalidone, mandelic acid and terbutaline was studied by reversed phase HPLC withβ -cyclodextrin and L-phenylalanine-Cu as chiral mobile phase additives. The method was applied to determination of amount of the enantiomers with good linear relationship and selection.2. Based on chemical thermodynamic theory and mass balance, the theory for chiral extraction was studied. It is pointed that enantiomeric separation is dependent on the difference in free energy between the two diastereomeric complexes formed by a chiral selector and enantiomers, - A ( A G). Only if separation factor is more than 1, that is to say, - △(△G) is above 0, different degrees of separation of enantiomers can be achieved by chiral extraction.3. The influence of pH, organic solvents and the concentrations ofchiral selector on K, a and - A (A G) for ofloxacin, chlorthalidone and mandelic acid enantiomers, was investigated with tartaric acid derivatives as chiral selectors. The extraction performance and chiral recognition mechanism were studied.4. Distribution behaviors of terbutaline enantiomers were examined in the aqueous-organic of a two-phase system containing one of tartaric acid derivatives with Na-tetraphenylborate (NaBPlit) as a lipophlilic phase transfer reagent. BPri4~ can form lipophilic salt complexes with terbutaline enantiomers, which facilitates the solubility of the enantiomers in the organic phase. Partition coefficients increase with the rise of the concentrations of NaBPh4 at cost of loss of separation factor of terbutaline enantiomers by extraction. 0.0045 mol/L NaBPlij is suitable to separate terbutaline enantiomers.5. N--dodecyl-L-proline(Ci2-Pro) and N--dodecyl-L-hydroxyprol-ine(Ci2-Hyp) were synthesized. With Ci2-Pro and Ci2-Hyp derivatives as chiral selectors, respectively, influence of pH value, Cu2+ concentrations and organic solvents on extraction performance was investigated. It is found that C-pro and Ci2-Hyp have stronger stereoselectivity for ofloxacin and mandelic acid enantiomers than tartaric acid derivatives.6. Based on mass balance and fractional achiral extraction theory, fractional chiral extraction was studied, and mathematical models of R/S or S/R-NTU and Y-NTU were established. The models were simulated by Visual Basic program, and provided for separation of enantiomers by countercurrently fractional extraction with hollow fiber membrane.7. Polysulfone hollow fiber membranes were modified by filling hydrogel and immersing in NaH2PO4/H3PO4 buffer solution, respectively. Ofloxacin enantiomers were separated by hollow fiber membrane extraction. Good separation results were obtained with 3.4 of the ratio of the concentrations of ofloxacin enantiomers by 2 X 5 hollow fiber membrane modules filled with hydrogel.8. Based on chiral O/W extraction theory, support-liquid membrane extraction with two organic phases containing D-selector and L-selector, respectively, was studied.
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