Abstract The development of stability-indicating method with isocratic elution mode based on micellar liquid chromatography for the analysis of cilazapril, hydrochlorothiazide and their degradation products was the primary aim of the present research. Since this could be done using different methodologies, two approaches were selected and comprehensively compared. The first one was risk based quality by design concept adopted by many analysts since it ensures development of robust analytical methods. The second one was multicriteria decision making approach currently interpreted in a form of experimental design complemented with grid point search is well established over past decades as a very useful way to govern analytical method development. Major drawback of later approach, related to method robustness evaluation, was discounted through proposition of simple and efficient computational procedure. Both methodologies ultimately resulted in successful chromatographic separations of all investigated substances which included analysis on XTerra RP 18 (3.9 × 150 mm, 5 μm) column with temperature set at 30 °C, mobile phase consisting of acetonitrile and Brij L23 aqueous solution (18 mmol L−1, pH 3.8) in ratio 13:87 (%, v/v) pumped at 1 mL min−1 flow rate while UV detection was performed at 215 nm. Both the 3D representation of a design space as well as grid obtained with later approach pointed out that the method performance criteria would not be compromised when amount of acetonitrile amount varies in range 12–14% (v/v), pH of the water phase in range 3.4–4.0, while concentration of Brij L23 aqueous solution can be within 15–20 mmol L−1. Hence, although the method development was based on different starting hypothesis, both methodologies enabled achievement of reliable and robust analytical methods that could serve in monitoring of cilazaprile and hydrochlorothiazide combined dosage form stability.

中文翻译：

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AQbD 和网格点搜索方法在开发用于分析西拉普利和氢氯噻嗪剂型稳定性的胶束 HPLC 方法中的比较

摘要 本研究的主要目的是开发基于胶束液相色谱的等度洗脱模式的稳定性指示方法，用于分析西拉普利、氢氯噻嗪及其降解产物。由于这可以使用不同的方法来完成，因此选择了两种方法并进行了全面比较。第一个是许多分析师采用的基于风险的质量设计概念，因为它确保开发稳健的分析方法。第二个是目前以实验设计形式解释的多标准决策方法，网格点搜索在过去几十年中得到很好的证实，作为管理分析方法开发的一种非常有用的方法。后期方法的主要缺点，与方法稳健性评估有关，通过提出简单有效的计算程序而打折扣。两种方法最终都成功实现了所有研究物质的色谱分离，包括在 XTerra RP 18（3.9 × 150 mm，5 μm）色谱柱上进行分析，色谱柱温度设置为 30 °C，流动相由乙腈和 Brij L23 水溶液（18 mmol L-1, pH 3.8) 的比例为 13:87 (%, v/v) 以 1 mL min-1 流速泵送，而 UV 检测在 215 nm 处进行。设计空间的 3D 表示以及使用后来的方法获得的网格都指出，当乙腈的量在 12-14% (v/v)、水相的 pH 值范围内变化时，方法性能标准不会受到影响在 3.4-4.0 范围内，而 Brij L23 水溶液的浓度可以在 15-20 mmol L-1 范围内。因此，