HP-β-环糊精对盐酸舍曲林异构体手性选择包合和色谱保留行为影响的研究

Study on Chiral Selective Inclusion and Retention Characteristics of cis-trans Isomers and Enantiomers of Sertraline with HP-β-CD as a Mobile Phase Modifier

研究了不同色谱条件下HP β 环糊精(HP β CD)作为反相高效液相色谱(RP HPLC)手性添加剂对盐酸舍曲林异构体的手性选择性和色谱保留行为的影响。通过保留因子(k)的倒数1/k对[HP β CD]的良好线性关系证明HP β CD与盐酸舍曲林异构体形成了包合比为1∶1的包合物,并通过1/k对[HP β CD]的直线求得其结合常数。同时系统研究了pH值、缓冲液浓度(离子强度)、乙腈溶剂强度及温度对结合常数的影响,对结合常数与它们的关系做出了定量的描述;计算了手性分离过程中的热力学参数,并结合所计算的结合常数,研究了HP β CD对盐酸舍曲林异构体的手性识别能力的影响。结果表明,HP β CD与盐酸舍曲林异构体相互作用的结合常数的大小顺序与手性分离选择性的顺序相反,焓差(△j,i△H)和熵差(△j,i△S)越大,手性分离选择性也越大。实验得到的盐酸舍曲林异构体的焓差和熵差都是负值,说明盐酸舍曲林异构体的分离是焓驱动的分离过程;温度对结合常数影响的实验结果表明,HP β CD对盐酸舍曲林异构体的包合过程是一个放热行为,与通过计算热力学参数得到的结果一致。

The effect of the inclusion complex formation of cis-trans isomers and enantiomers of (sertraline) with added hydroxypropyl-β-cyclodextrin (HP-β-CD) in the reversed-phase high performance liquid chromatographic (RP-HPLC) mobile phase on the retention and selectivity has been (investigated.) Graphs of 1/k vs ([HP-β-CD]) in different experimental conditions gave good linear relationships, indicating the stoichiometry ratio of 1∶1. The binding constants between HP-β-CD and cis-trans (isomers) and enantiomers of sertraline were calculated by using the liquid chromatographic retention (values.) Meanwhile, the influences of pH value, buffer ionic strength, concentration of organic modifier and temperature on the binding constant have been studied in detail. Quantitative equations were (obtained) for the correlations between the binding constants and the above influencing parameters. On the other hand, the thermodynamic parameters of the inclusion complexes were determined for the four inclusion complexes. The study characterized the chiral recognition selectivity between sertraline isomers and HP-β-CD. It was demonstrated that the chiral selectivity values were in the same (sequence) as △_(j,i)△H and △_(j,i)△S and opposite order against the binding constants of inclusion (complexes.) Both enthalpic and entropic terms were negative for cis-trans isomers and enantiomers of (sertraline.) It was confirmed that enthalpy-driven separations occurred in consistency with the results. The influence of temperature on retention behavior showed that the process of inclusion was (exothermic,) in consistency with the calculated thermodynamic parameters.