β-环糊精及其衍生物手性添加剂HPLC法拆分氯噻酮对映体过程热力学研究

Thermodynamic study on enantioresolution of chlorthalidone by high performance liquid chromatography using β-cyclodextrin and its derivatives as chiral additives

以Me-β-环糊精为手性流动相添加剂，于Lichrospher C18反相柱上建立了氯噻酮对映体高效液相色谱拆分方法，同时改进了β-环糊精、HP-β-环糊精为手性流动相添加剂拆分氯噻酮对映体的色谱条件，并着重研究了在25-45℃范围内Me-β-CD、β-CD和HP-β-CD为手性流动相添加剂拆分氯噻酮对映体的过程热力学并结合手性药物氯噻酮所得的热力学数据对环糊精及其衍生物拆分能力的差异进行了比较和分析。结果表明都属于焓控过程，其拆分能力的不同主要是因为手性添加剂与对映体形成氢键作用、空间位阻效应和立体构象匹配程度存在差异。

Chromatographic separation of chlorthalidone has been studied using β-cyclodextrins as mobile phase additives and appropriate analytical conditions have been established. The effect of mobile-phase composition was researched in detail. The effect of different temperatures （25 - 45 ℃ ） and corresponding thermodynamic parameters on the chromatographic behaviour of chlorthalidone enantiomers were tested using β-cyclodextrins as chiral additives, respectively. The results obtained indicated the enthalpic contribution to the overall chlorthalidone enantiomers was more significant than that of entropic one. The different resolution abilities of three type cyclodextrins were detemined by several interactions, including hydrogen bond interactions, space domino effect and different stereoconfigutrations.