Background In the recent scenario of green chemistry, the usage of organic solvents should be minimized in the development of analytical methods for the safety of the environment and analysts. Objective An RP-HPLC method has been developed as an economical and eco-friendly alternative to published RP-HPLC methods for the analysis of fixed-dose combinations (FDCs) of anti-hypertensive drugs, for saving time, resources, costs, and organic solvent. Methods The method has been developed through the implementation of an enhanced analytical quality by design (AQbD) approach using a design of experiment (DoE)-based analytical failure mode critical effect analysis (AFMCEA). The AFMCEA was performed by identifying potential analytical failure modes and assessing their risk using risk priority number ranking and filtering. The DoE-based AFMCEA was implemented for response surface analysis and mitigation of high-risk analytical failure modes by Box-Behnken design (BBD). The method operable design ranges and control strategy were set for lifecycle management of the developed method. Results The RP-HPLC method was developed using a Shimpack octadecyl silane (ODS) C18 column and acetonitrile–water (pH 6.2; 42:58 %, v/v). The method was validated as per ICH Q2 (R1) guidelines. The method was applied for the synchronous assay of 15 FDCs of anti-hypertensive drugs. Conclusion The developed method has fulfilled the requirements of numerous published RP-HPLC and HPTLC methods. Hence, this method is a multipurpose chromatography method for synchronous estimation of FDC products of anti-hypertensive drugs. This method can be used as a multipurpose (M), economical (E), eco-friendly (E), and rapid (R), MEER-RP-HPLC for quality control of multiple FDCs of anti-hypertensive drugs in the pharmaceutical industry. Highlights Development of a MEER-RP-HPLC method for synchronous estimation of 15 pharmaceutical dosage forms of anti-hypertensive drugs. Implementation of an enhanced AQbD approach using a DoE-based AFMCEA to develop the method which was applied to the assay of 15 anti-hypertensive dosage forms.

中文翻译：

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基于 DoE 的分析-FMCEA 用于增强 AQbD 方法的 MEER-RP-HPLC 方法同步估计 15 种抗高血压药物剂型

背景 在最近的绿色化学情景中，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有机溶剂的使用。目的 已开发出一种 RP-HPLC 方法，作为已发表的 RP-HPLC 方法的经济且环保的替代方法，用于分析抗高血压药物的固定剂量组合 (FDC)，以节省时间、资源、成本和有机物溶剂。方法 该方法是通过使用基于实验设计 (DoE) 的分析失效模式临界效应分析 (AFMCEA) 实施增强的设计分析质量 (AQbD) 方法而开发的。AFMCEA 是通过识别潜在的分析故障模式并使用风险优先级编号排序和过滤评估其风险来执行的。基于 DoE 的 AFMCEA 通过 Box-Behnken 设计 (BBD) 用于响应面分析和缓解高风险分析故障模式。为所开发方法的生命周期管理设定了方法可操作设计范围和控制策略。结果 使用 Shimpack 十八烷基硅烷 (ODS) C18 色谱柱和乙腈-水（pH 6.2；42:58 %，v/v）开发了 RP-HPLC 方法。该方法根据 ICH Q2 (R1) 指南进行了验证。该方法应用于15种降压药FDCs的同步检测。结论 所开发的方法满足了许多已发表的 RP-HPLC 和 HPTLC 方法的要求。因此，该方法是一种用于同步估计抗高血压药物的 FDC 产物的多用途色谱方法。该方法可作为多用途（M）、经济（E）、环保 (E) 和快速 (R) MEER-RP-HPLC 用于制药行业抗高血压药物多种 FDC 的质量控制。重点开发了一种用于同步估计 15 种抗高血压药物药物剂型的 MEER-RP-HPLC 方法。使用基于 DoE 的 AFMCEA 实施增强的 AQbD 方法，以开发应用于 15 种抗高血压剂型测定的方法。