酸糖蛋白手性柱分离6种手性化合物

The Separation of Enantiomers by Acid Glycoprotein Chiral Stationary Phase

通过考察缓冲液种类、浓度及其pH值对对映体在手性柱上的保留和分离行为的影响,以及流动相中加入不同种类、不同浓度的不带电荷的有机溶剂乙腈、甲醇、正丙醇、异丙醇、流动相流速和柱温对对映体分离能力的影响,优化了含碳手性中心的碱性药物苯丙哌林、酸性化合物MT-A5及MT-酸和含硫手性中心的质子泵抑制剂奥美拉唑、泮托拉唑、雷贝拉唑对映体分离条件,最佳手性分离条件为:苯丙哌林,0.05 mol/L磷酸二氢铵缓冲液(pH 3.0)-乙腈(95∶5,V/V)为流动相,流速为0.7 mL/m in,柱温为20℃;MT-A5及MT-酸,流动相为0.01 mol/L醋酸铵缓冲液(pH 5.0)-乙腈(74∶26,V/V),流速为0.9 mL/m in,柱温为20℃;泮托拉唑,流动相为10 mmol/L醋酸铵缓冲液(pH 5.5)-乙腈(93∶7,V/V),流速为0.9 mL/m in;柱温为20℃;奥美拉唑和雷贝拉唑,流动相为0.01 mol/L醋酸铵缓冲液(pH 3.0)-乙腈(95∶5,V/V),流速为0.7 mL/m in,柱温为20℃。实现了应用高效液相色谱法在α1-酸糖蛋白手性柱上对上述化合物的对映体分离,并成功用于手性药物合成中的对映体过量百分率的测定。

The separations of the enantiomers of benproperine, MT-A5, MT-Acid, and proton pump inhibitor, including omeprazole, pantoprazole, and rabeprazole by high performance liquid chromatography （HPLC） on a α1-acid glycoprotein chiral stationary phase have been accomplished. The effect of pH value, the concentration, and the kind of buffer on the chromatographic performance of enantiomers or racemates was examined. The influence of properties and concentration of organic solvents （acetonitrile, methanol, n-propanol, and isopropanol） in mobile phase, the flow rate, and the temperature on retention time and enantioselective separation of racematcs was also studied. The optimal experimental conditions for these compounds were as follows： benproperine, mobile phase： 0.05 mol/L NH4H2PO4 （pH 3.0）-acetonitrile （95：5, V/V）, flow rate： 0. 7 mL/min; MT-A5 and MT-Acid, mobile phase： 0. 051 mol/L ammonium acetate （pH 5. 0）-acetonitrile （74： 26, V/V）, flow rate： 0.7 mL/min; pantoprazole, mobile phase： 0.01 moL/L ammonium acetate （pH 5.5 ）-acetonitrile （93：7, V/V）, flow rate： 0.9 mL/min; omeprazole and rabeprazole, mobile phase： 0.01 moL/L ammonium acetate （pH 3.0）-acetonitrile （95：5, V/V）, flow rate： 0.7 mL/min ; all the temperatures were set at 20℃. These methods had been successfully applied to the determination of the enantiomeric excess of the drug enantiomers.