We developed a novel, rapid, sensitive, and stability-indicating UHPLC method for quantification of Perindopril (PER), Amlodipine (AML), and their impurities in pharmaceutical formulations. The optimum chromatographic separation was achieved in gradient elution mode using Agilent SB C18 (50 × 3.0 mm, 1.8 μm) column. A buffer containing 0.1% perchloric acid and acetonitrile was used as a mobile phase component. The flow rate was 0.8 mL per minute and the detection wavelength at 215 nm was optimized. We also set an injection volume of 10 μL and the column thermostat at 60 °C. The findings were interesting: Resolution for PER, AML, and nine impurities is more than 1.5 for any pair of compounds. The proposed method is validated according to the ICH guidelines, and it is accurate, precise, linear, rugged, and robust. Specificity study proves the method efficiency in estimating PER, AML, and their related substances within the same run. The drug product was subjected to various stress degradation conditions and a significant amount of degradation in acid hydrolysis was observed. We proved the method robustness of chromatographic conditions by applying response surface methodology as a tool under a QbD approach and established the design space. This method is found to be stability-indicating and can be applied for analysis in quality control laboratories.

中文翻译：

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用于药物制剂中培哚普利、氨氯地平及其杂质定量的新型稳定性指示 UHPLC 方法开发和验证：QbD 方法的应用

我们开发了一种新颖、快速、灵敏且具有稳定性指示的 UHPLC 方法，用于对药物制剂中的培哚普利 (PER)、氨氯地平 (AML) 及其杂质进行定量。使用 Agilent SB C18（50 × 3.0 mm，1.8 μm）色谱柱在梯度洗脱模式下实现了最佳色谱分离。使用含有 0.1% 高氯酸和乙腈的缓冲液作为流动相组分。流速为每分钟 0.8 mL，优化了 215 nm 的检测波长。我们还设置了 10 μL 的进样体积和 60 °C 的柱温箱。结果很有趣：任何一对化合物的 PER、AML 和九种杂质的分辨率都超过 1.5。所提出的方法根据 ICH 指南进行了验证，并且它准确、精确、线性、坚固且稳健。特异性研究证明了该方法在一次运行中估算 PER、AML 及其相关物质的效率。药物产品经受各种应力降解条件，并观察到大量的酸水解降解。我们通过应用响应面方法作为 QbD 方法下的工具证明了色谱条件的方法稳健性，并建立了设计空间。发现该方法具有稳定性指示作用，可用于质量控制实验室的分析。我们通过应用响应面方法作为 QbD 方法下的工具证明了色谱条件的方法稳健性，并建立了设计空间。发现该方法具有稳定性指示作用，可用于质量控制实验室的分析。我们通过应用响应面方法作为 QbD 方法下的工具证明了色谱条件的方法稳健性，并建立了设计空间。发现该方法具有稳定性指示作用，可用于质量控制实验室的分析。