In this work, enantiomeric separation of a drug combination of two chiral drugs, namely, atenolol and chlorthalidone, is described. Prior investigation of the effect of different variables on the resolution of the enantiomers' peaks and the total run time represented by the retention time of the last eluted peak was conducted using face-centered composite design. Twenty-two experiments were carried out by varying the chiral stationary phase type as a categorical factor and mobile phase composition including the percentage of ethanol and percentage of diethylamine as continuous factors. According to the optimization process, a mobile phase consisting of hexane:ethanol:DEA:TFA (60:40:0.2:0.1%, v/v/v/v) pumped at flow rate 1 ml min⁻¹ onto Lux-Cellulose 2 stationary phase was applied for the chiral separation and quantification of the drug combination at 230 nm. Application of the developed method to the pharmaceutical formulation of this combination was successfully performed, and satisfactory percentage of recoveries was obtained. The method was also fully validated following International Conference on Harmonization (ICH) guidelines. This method could be of high value and relevance for application in quality control laboratories.

中文翻译：

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使用多糖基固定相的高效液相色谱同时分离阿替洛尔和氯噻酮二元混合物对映体的实验设计优化

在这项工作中，描述了两种手性药物（即阿替洛尔和氯噻酮）的药物组合的对映体分离。使用面心复合设计对不同变量对对映异构体峰的分辨率和由最后一个洗脱峰的保留时间表示的总运行时间的影响进行了事先调查。通过改变手性固定相类型作为分类因素和流动相组成（包括乙醇的百分比和二乙胺的百分比作为连续因素）进行了 22 个实验。根据优化过程，由己烷:乙醇:DEA:TFA (60:40:0.2:0.1%, v/v/v/v) 组成的流动相以 1 ml min ^{-1 的}流速泵送使用 Lux-Cellulose 2 固定相在 230 nm 处对药物组合进行手性分离和定量。成功地将开发的方法应用于该组合的药物制剂，并获得了令人满意的回收率。根据国际协调会议 (ICH) 指南，该方法也得到了充分验证。这种方法对于质量控制实验室的应用可能具有很高的价值和相关性。