According to the green chemistry approach, the usage of carcinogenic and teratogenic organic solvents should be minimized in the development of the analytical method for the safety of the environment and analysts. According to the literature review, no high-performance thin-layer chromatographic (HPTLC) method has been reported yet for concomitant analysis of azilsartan medoxomil (AZM), chlorthalidone (CTD) and cilnidipine (CDP) in human plasma. Hence, a robust and accurate HPTLC method has been developed using safe and non-toxic organic solvents for the concomitant analysis of AZM, CTD and CDP in human plasma, fixed-dose combinations (FDCs) and laboratory mixtures. The HPTLC method was developed by the implementation of the analytical quality by design approach using principles of quality risk management and design of experiments (DoE) for regulatory compliance. The principal component analysis was applied for the risk assessment and analysis of potential method variables in the method development. The principle of DoE was used for the response surface modeling to link identified critical method risk parameters with critical method performance attributes using full factorial design (FFD). The method operable design region and analytical control space were navigated for the optimization of the method as per quality target analytical profile. The developed method was also applied for concomitant analysis of AZM, CTD and CDP in their FDCs and laboratory mixture and results were found in good agreement with the labeled amount of the respective drug.

中文翻译：

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基于化学计量学和绿色化学的色谱分析人血浆中的阿齐沙坦酯、西尼地平和氯噻酮，采用分析质量设计方法


根据绿色化学方法，为了环境和分析人员的安全，在开发分析方法时应尽量减少致癌和致畸有机溶剂的使用。根据文献综述，目前尚未报道用于同时分析人血浆中阿齐沙坦酯（AZM）、氯噻酮（CTD）和西尼地平（CDP）的高效薄层色谱（HPTLC）方法。因此，我们使用安全无毒的有机溶剂开发了一种稳健且准确的 HPTLC 方法，用于同时分析人血浆、固定剂量组合 (FDC) 和实验室混合物中的 AZM、CTD 和 CDP。 HPTLC 方法是通过使用质量风险管理和实验设计 (DoE) 原则实施分析质量设计方法而开发的，以确保合规性。主成分分析用于方法开发中潜在方法变量的风险评估和分析。 DoE 的原理用于响应面建模，以使用全因子设计 (FFD) 将已识别的关键方法风险参数与关键方法性能属性联系起来。根据质量目标分析概况，导航方法可操作设计区域和分析控制空间，以优化方法。所开发的方法还应用于 FDC 和实验室混合物中 AZM、CTD 和 CDP 的伴随分析，结果发现与相应药物的标签量非常一致。