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使用实验设计方法比较非索罗定电化学氧化中的静态和动态模式。

Comparison of static and dynamic mode in the electrochemical oxidation of fesoterodine with the use of experimental design approach.

作者信息

Bartosińska Ewa, Kozlík Petr, Kubíčková Anna, Heřt Jakub, Fischer Jan, Křížek Tomáš

机构信息

Charles University, Faculty of Science, Department of Analytical Chemistry, Albertov 6, Prague, 12843, Czech Republic.

Zentiva, K.s. U Kabelovny 130, 102 37, Prague, Czech Republic.

出版信息

Talanta. 2021 May 1;226:122141. doi: 10.1016/j.talanta.2021.122141. Epub 2021 Jan 28.

DOI:10.1016/j.talanta.2021.122141
PMID:33676692
Abstract

Electrochemical conversion of fesoterodine to one of its oxidation products was evaluated with the application of the wall-jet flow cell. A traditional, "static" mode of electrolysis was compared with the "dynamic" mode of cell performance. For statistical assessment of the data, experiments were planned and performed with the application of design of experiments approach, namely Taguchi L18 design. After screening phase, the experimental settings were broadened or adjusted according to the results and optimization was performed. All of the samples were electrolysed with the use of chronoamperometric method in a three electrode system. The electrolysed samples were analysed using UHPLC-PDA-QDA method. The chromatographic run was performed in gradient elution with the application of C8 column. The response was expressed as % area of the main peak found with the PDA detection method whereas QDA detector was used in positive SIM mode for structural confirmation. All data obtained for both screening and optimization were treated together and linear models were adjusted. The use of large-surface glassy carbon electrode along with pH~7 were found to be the most significant factors influencing electrochemical oxidation of fesoterodine in both modes. The major differences were identified in terms of voltage applied to the electrodes which yielded the highest amounts of oxidation product. Evolution of electrochemical methods may serve as complementary technique in stress degradation studies in pharmaceutical industry.

摘要

采用壁流池评估非索罗定向其一种氧化产物的电化学转化。将传统的“静态”电解模式与电解池的“动态”性能模式进行比较。为了对数据进行统计评估,采用实验设计方法(即田口L18设计)来规划和进行实验。在筛选阶段之后,根据结果扩大或调整实验设置并进行优化。所有样品均在三电极系统中采用计时电流法进行电解。采用UHPLC-PDA-QDA法对电解后的样品进行分析。色谱分析采用C8柱进行梯度洗脱。响应以PDA检测法测得的主峰面积百分比表示,而QDA检测器则用于正离子选择离子监测模式进行结构确证。将筛选和优化过程中获得的所有数据合并处理并拟合线性模型。发现在两种模式下,使用大表面积玻碳电极以及pH约为7是影响非索罗定电化学氧化的最显著因素。在施加于电极的电压方面发现了主要差异,该电压产生了最高量的氧化产物。电化学方法的发展可作为制药行业应力降解研究中的补充技术。

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