HP-β-CD手性流动相HPLC法拆分萘普生对映体的色谱保留机制和拆分机理研究

Study on Retention Characteristics and Separation Mechanism of Enantiomers of Naproxen with HP_β_CD as a Mobile Phase Modifier in HPLC

研究了HPLC法羟丙基_β_环糊精(HP_β_CD)手性流动相添加剂对萘普生对映体的保留机制,建立了保留因子与[CD]、[H+]、包结常数以及萘普生的解离常数的关系式,并结合实验对此关系式进行了验证,结果表明此关系式对手性添加剂、pH等因素对拆分的影响具有一定的理论指导。保留因子(k)的倒数1k对HP_β_CD的浓度呈良好的线性关系,证明HP_β_CD与萘普生对映体形成的包合比是11包合物。计算了手性分离过程中的热力学参数,结果表明HP_β_CD对萘普生对映体的分离过程主要是一个焓驱动的过程,包合过程是一个放热过程。通过比较手性选择体结构,探讨了HP_β_CD拆分萘普生对映体的机理,进一步分析表明HP_β_CD能拆分萘普生对映体的主要因素是尺寸大小相匹配、构象诱导作用和偶极_偶极作用。

Enantiomers of naproxen with added hydroxypropyl-β- cyclodextrin （ HP- β- CD） in high performance liquid chromatographic （HPLC） mobile phase on the retention had been investigated. Relationship equations of capacity factor with [CD] ,[H^＋ ] and inclusion complex and dissociation constants of naproxen were built and demonstrated by experiments, results showed that the relationship equation can forecast on separation process. Graph of Ilk vs [ HP-β-CD] gave good linear relationship, indicating the stoichiometric ratio of 1/1. On the other hand, the thermodynamic parameters of inclusion complexes were determined, it was demonstrated that separation of naproxen enantiomers was enthalpy-driven process, and the process of inclusion was exothermic. In addition, separation mechanism on naproxen enantiomers with HP-β-CD as a mobile phase modifier was discussed by comparing the structure of cyclodextrins. The primary factors that HP-β-CD can separate naproxen enantiomers are the size-size matches, the conformation induction and the dipole-dipole interaction.