The combined implementation of quality by design principles and green analytical chemistry leads to development of green micellar HPLC method for analysis of atorvastatin calcium and amlodipine besylate in binary mixtures and in their tablet dosage forms within 8 min. A two-level fractional factorial design was implemented for screening of different method parameters affecting chromatographic responses. Box–Behnken design was then used to study and optimize the most critical parameters. The optimum chromatographic conditions obtained from Box–Behnken design involved the use of a mixture of 0.17 M sodium dodecyl sulfate solution adjusted to pH 2.9 and 10%v/v n-butanol as mobile phase at a flow rate of 1.5 mL min−1 and column temperature kept at 45 ºC. The stationary phase was X-Bridge™ (150 mm × 4.6 mm, 5 μm) column. The fluorescence detection was programmed at 276/378 nm (excitation/ emission) for the first 5 mins for atorvastatin then switched to 366/442 nm (excitation/emission) for amlodipine. A linear response was obtained over the ranges of 0.2–25 μg mL−1 for both drugs. The proposed method was validated and successfully implemented for the simultaneous determination of cited drugs in their different tablet dosage forms. The method was additionally applied to content uniformity testing according to the official guidelines. The application of quality by design principles and green analytical chemistry results in development of robust green method with less trial and error experiments.

中文翻译：

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创新质量设计方法，用于开发同时测定阿托伐他汀和氨氯地平的绿色胶束 HPLC 方法

质量源于设计原则和绿色分析化学的结合实现了绿色胶束 HPLC 方法的发展，用于在 8 分钟内分析二元混合物及其片剂剂型中的阿托伐他汀钙和苯磺酸氨氯地平。实施了两级部分因子设计来筛选影响色谱响应的不同方法参数。然后使用 Box-Behnken 设计来研究和优化最关键的参数。从 Box-Behnken 设计获得的最佳色谱条件包括使用 0.17 M 十二烷基硫酸钠溶液调节至 pH 2.9 和 10%v/v 正丁醇的混合物作为流动相，流速为 1.5 mL min-1 和柱温保持在 45 ºC。固定相为 X-Bridge™（150 mm × 4.6 mm，5 μm）柱。对于阿托伐他汀，荧光检测在前 5 分钟编程为 276/378 nm（激发/发射），然后对于氨氯地平切换到 366/442 nm（激发/发射）。两种药物在 0.2–25 μg mL-1 范围内均获得线性响应。所提出的方法经过验证并成功实施，用于同时测定不同片剂剂型中的引用药物。根据官方指南，该方法还应用于含量均匀性测试。质量源于设计原则和绿色分析化学的应用导致开发出稳健的绿色方法，减少反复试验。两种药物在 0.2–25 μg mL-1 范围内均获得线性响应。所提出的方法经过验证并成功实施，用于同时测定不同片剂剂型中的引用药物。根据官方指南，该方法还应用于含量均匀性测试。质量源于设计原则和绿色分析化学的应用导致开发出稳健的绿色方法，减少反复试验。两种药物在 0.2–25 μg mL-1 范围内均获得线性响应。所提出的方法经过验证并成功实施，用于同时测定不同片剂剂型中的引用药物。根据官方指南，该方法还应用于含量均匀性测试。质量源于设计原则和绿色分析化学的应用导致开发出稳健的绿色方法，减少反复试验。