A precise, robust and accurate high-performance thin-layer chromatography (HPTLC) method has been developed for the simultaneous estimation of chlorthalidone and metoprolol succinate using analytical quality by design approach based on principles of quality risk management and design of experiments. The quality risk management was performed by the identification of probable method risk parameters and their assessment by allotting a risk priority number. Design of experiments was performed by Taguchi OA screening design and central composite response surface analysis using resolution between peaks as critical method performance attributes. A total of seven method risk parameters were screened for their main effect on the resolution between peaks using Design-Expert software (trial version). The main effect of three method parameters were found critical and needed to be optimised for method development. Hence, response surface analysis was done by linking the effects of critical method parameters, mobile phase composition, volume of modifier and chamber saturation time with the resolution between peaks by central composite design. Method operable design region was navigated for development of the method as per the analytical target profile. Chromatographic separation was performed using silica gel GF₂₅₄ as the stationary phase and toluene‒methanol‒triethylamine (8:2:0.5, V/V) as the mobile phase in twin-trough chamber keeping saturation time of 15 min. The developed method was validated as per the International Council for Harmonisation (ICH) Q2 (R1) guideline. The developed method was applied for the assay of combined pharmaceutical dosage forms of chlorthalidone and metoprolol succinate and the results were found in good agreement with their labelled claim.

基于质量风险管理和实验设计原则，使用分析质量设计方法开发了一种精确、稳健和准确的高效薄层色谱 (HPTLC) 方法，用于同时评估氯噻酮和琥珀酸美托洛尔。质量风险管理是通过确定可能的方法风险参数并通过分配风险优先级编号对其进行评估来执行的。实验设计通过田口 OA 筛选设计和中心复合响应面分析进行，使用峰之间的分辨率作为关键的方法性能属性。使用 Design-Expert 软件（试用版）筛选了总共七个方法风险参数，以确定它们对峰间分辨率的主要影响。发现三个方法参数的主要影响至关重要，需要针对方法开发进行优化。因此，响应面分析是通过将关键方法参数、流动相组成、改性剂体积和腔室饱和时间的影响与中心复合设计峰之间的分辨率联系起来来完成的。根据分析目标配置文件导航方法可操作设计区域以开发方法。使用硅胶GF进行色谱分离 根据分析目标配置文件导航方法可操作设计区域以开发方法。使用硅胶GF进行色谱分离 根据分析目标配置文件导航方法可操作设计区域以开发方法。使用硅胶GF进行色谱分离₂₅₄为固定相，甲苯-甲醇-三乙胺（8：2：0.5，V/V）为流动相，在双槽室中保持饱和时间为15分钟。根据国际协调委员会 (ICH) Q2 (R1) 指南对开发的方法进行了验证。将开发的方法应用于氯噻酮和琥珀酸美托洛尔的复方药物剂型的测定，发现结果与其标签声明非常吻合。