Department of Chemistry "U. Schiff", University of Florence, 50019 Sesto Fiorentino, Italy.
Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy.
Molecules. 2023 Jun 13;28(12):4747. doi: 10.3390/molecules28124747.
In 2022, the International Council for Harmonisation released draft guidelines Q2(R2) and Q14, intending to specify the development and validation activities that should be carried out during the lifespan of an analytical technique addressed to assess the quality of medicinal products. In the present study, these recommendations were implemented in Capillary Electrophoresis method development for the quality control of a drug product containing trimecaine, by applying Analytical Quality by Design. According to the Analytical Target Profile, the procedure should be able to simultaneously quantify trimecaine and its four impurities, with specified analytical performances. The selected operative mode was Micellar ElectroKinetic Chromatography employing sodium dodecyl sulfate micelles supplemented with dimethyl-β-cyclodextrin, in a phosphate-borate buffer. The Knowledge Space was investigated through a screening matrix encompassing the composition of the background electrolyte and the instrumental settings. The Critical Method Attributes were identified as analysis time, efficiency, and critical resolution values. Response Surface Methodology and Monte Carlo Simulations allowed the definition of the Method Operable Design Region: 21-26 mM phosphate-borate buffer pH 9.50-9.77; 65.0 mM sodium dodecyl sulfate; 0.25-1.29% /-butanol; 21-26 mM dimethyl-β-cyclodextrin; temperature, 22 °C; voltage, 23-29 kV. The method was validated and applied to ampoules drug products.
2022 年，国际协调理事会发布了草案指南 Q2(R2)和 Q14，旨在规定应在分析技术的生命周期内开展的开发和验证活动，以评估药品的质量。在本研究中，这些建议在针对含有三甲卡因的药物产品质量控制的毛细管电泳方法开发中得到了实施，采用了分析质量设计。根据分析目标概况，该程序应该能够同时定量测定三甲卡因及其四种杂质，并具有指定的分析性能。选择的操作模式是胶束电动色谱法，使用十二烷基硫酸钠胶束，并添加二甲基-β-环糊精，在磷酸盐-硼酸盐缓冲液中。通过一个包含背景电解质组成和仪器设置的筛选矩阵，研究了知识空间。关键方法属性被确定为分析时间、效率和关键分辨率值。响应面法和蒙特卡罗模拟允许定义方法可操作设计区域：21-26mM 磷酸盐-硼酸盐缓冲液 pH9.50-9.77；65.0mM 十二烷基硫酸钠；0.25-1.29%/-丁醇；21-26mM 二甲基-β-环糊精；温度 22°C；电压 23-29kV。该方法得到了验证，并应用于安瓿药物产品。
