Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Mar 1;1166:122549. doi: 10.1016/j.jchromb.2021.122549. Epub 2021 Jan 20.
The persistent introduction of new β-blockers motivates the demand for optimizing RP-HPLC well-designed analytical procedures that could be applied to this structurally related and commonly prescribed pharmacological group in order to reduce time and chemicals consumption in quality control units. Betoxolol HCl (BEX) and Carvidolol (CAR) were selected as representative examples to conduct predictive studies based on two complementary approaches, Quality by design (QBD) and Quantitative structure property relationship (QSPR). In concern QBD, a Box-Behnken design was adopted at variable chromatographic parameters to achieve the most proper conditions that might be applied for efficient analysis of the majority of group members. On the other hand, the retention time was chosen as the target property in the QSPR study that was conducted onto seven β. blockers (the two investigated drugs in addition to five other β. blockers) to find the best correlated molecular descriptors to the retention behavior. Both external and internal validation studies have comparable quality with training levels. Hence a simple selection algorithm of conventional features provides robust confirmatory predictive QBD and QSPR models. Derringer's desirability function as as a multi-criteria approach was applied for getting the optimum chromatographic analysis conditions. Efficient analysis of BET and CAR was achieved at column temperatures of 26.00 and 27.50 °C, respectively using acetonitrile and phosphate buffer (pH 4.55) 70:30 v/v as a mobile phase with a flow rate of 1.00 mL/min, and UV detection at 220 nm. The method was validated in accordance to ICH guidelines, and had exhibited acceptable precision, accuracy, linearity, and robustness.
新型β受体阻滞剂的不断引入促使人们需要优化反相高效液相色谱法（RP-HPLC）的分析程序，以便对该结构相关且广泛应用于临床的药物治疗组进行分析，从而减少质量控制部门的时间和化学物质消耗。本研究选择盐酸倍他洛尔（BEX）和卡维地洛（CAR）作为代表性药物，通过两种互补的方法（质量源于设计（QbD）和定量构效关系（QSPR））进行预测研究。在 QbD 方面，采用 Box-Behnken 设计对色谱参数进行了变量考察，以获得适用于大多数成员高效分析的最佳条件。另一方面，在 QSPR 研究中，保留时间被选为目标性质，对 7 种β受体阻滞剂（除上述两种药物外，还包括 5 种其他β受体阻滞剂）进行研究，以寻找与保留行为相关性最好的分子描述符。外部和内部验证研究均具有相当的质量和训练水平。因此，常规特征的简单选择算法可提供稳健的确认性预测 QbD 和 QSPR 模型。Derringer 的理想函数作为一种多标准方法，用于获得最佳的色谱分析条件。在柱温 26.00 和 27.50°C 下，分别使用乙腈和磷酸盐缓冲液（pH 4.55）70:30（v/v）作为流动相，流速为 1.00 mL/min，在 220nm 处进行检测，实现了 BET 和 CAR 的高效分析。该方法根据 ICH 指南进行了验证，具有良好的精密度、准确度、线性和稳健性。
