A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity and of impurities of the chiral calcimimetic drug cinacalcet hydrochloride has been developed following Quality by Design principles. The scouting phase was aimed to select the separation operative mode and to identify a suitable chiral selector. Among the tested cyclodextrins, (2-carboxyethyl)-β-cyclodextrin and (2-hydroxypropyl)-γ-cyclodextrin (HPγCyD) showed good chiral resolving capabilities. The selected separation system was solvent-modified capillary zone electrophoresis with the addition of HPγCyD and methanol. Voltage, buffer pH, methanol concentration and HPγCyD concentration were investigated as critical method parameters by a multivariate strategy. Critical method attributes were represented by enantioresolution and analysis time. A Box-Behnken Design allowed the contour plots to be drawn and quadratic and interaction effects to be highlighted. The Method Operable Design Region (MODR) was identified by applying Monte-Carlo simulations and corresponded to the multidimensional zone where both the critical method attributes fulfilled the requirements with a desired probability π ≥ 90%. The working conditions, with the MODR limits, corresponded to the following: capillary length, 48.5 cm; temperature, 18 °C; voltage, 26 kV (26–27 kV); background electrolyte, 150 mM phosphate buffer pH 2.70 (2.60–2.80), 3.1 mM (3.0–3.5 mM) HPγCyD; 2.00% (0.00–8.40%) v/v methanol. Robustness testing was carried out by a Plackett-Burman matrix and finally a method control strategy was defined. The complete separation of the analytes was obtained in about 10 min. The method was validated following the International Council for Harmonisation guidelines and was applied for the analysis of a real sample of cinacalcet hydrochloride tablets.

根据质量按设计原则，开发了一种同时测定手性拟钙剂西那卡塞盐酸盐对映体纯度和杂质的毛细管电泳方法。侦查阶段旨在选择分离操作模式并确定合适的手性选择剂。在测试的环糊精中，（2-羧乙基）-β-环糊精和（2-羟丙基）-γ-环糊精（HPγCyD）显示出良好的手性拆分能力。选择的分离系统是溶剂修饰的毛细管区带电泳，其中添加了HPγCyD和甲醇。通过多变量策略研究了电压，缓冲液pH，甲醇浓度和HPγCyD浓度作为关键方法参数。关键的方法属性用对映体拆分和分析时间表示。Box-Behnken设计允许绘制等高线图，并突出显示二次方和交互作用。方法可操作设计区域（MODR）通过应用蒙特卡洛模拟进行识别，并对应于多维区域，在该多维区域中，两个关键方法属性均以期望的概率π≥90％满足了要求。带有MODR限制的工作条件对应于以下条件：毛细管长度48.5厘米；温度18°C; 电压26 kV（26–27 kV）；背景电解质，150 mM磷酸盐缓冲液pH 2.70（2.60–2.80），3.1 mM（3.0–3.5 mM）HPγCyD；2.00％（0.00–8.40％）v / v甲醇。通过Plackett-Burman矩阵进行了稳健性测试，最后定义了一种方法控制策略。在约10分钟内即可完成分析物的完全分离。