In this paper, chromatographic anal

In this paper, chromatographic analysis of active substance olopatadine hydrochloride, which is used in eye drops as antihistaminic agent, and its impurity E isomer by hydrophilic interaction liquid chromatography (HILIC) and application of design of experiments (DoE) methodology are presented. In addition, benzalkonium chloride is very often used as a preservative in eye drops. Therefore, the evaluation of its chromatographic behavior in HILIC was carried out as well. In order to estimate
chromatographic behavior and set optimal chromatographic conditions, DoE methodology was applied. After the selection of important chromatographic factors, Box–Behnken design was utilized, and on the basis of the obtained models factor effects were examined.Then, multi-objective robust optimization is performed aiming to obtain chromatographic conditions that comply with several quality criteria
simultaneously: adequate and robust separation of critical peak pair and maximum retention of the first eluting peak. The optimal conditions are identified by using grid point search methodology. The experimental verification confirmed the adequacy of the defined optimal conditions.Finally, under optimal chromatographic conditions, the method was validated and applicability of the proposed method was confirmed.

結果 (中文) 1:

在本文中和由亲水作用色谱 (HILIC) 和活性物质奥洛他定盐酸的色谱分析设计中的应用及其杂质 E 异构体，用以在滴眼液中作为抗组胺剂 介绍了实验 (DoE) 方法。 此外，苯扎氯铵是很经常用作防腐剂的眼药水。 因此，在 HILIC 其色谱行为进行评价以及。 为了估计组分的色谱行为和设置优化的色谱条件下，方法的 DoE。 在选择后的色谱的重要因素，并利用框贝肯设计获得模型的基础上考察因素影响。 多目标鲁棒优化执行旨在获得遵守几个质量标准，然后的色谱条件同时︰ 足够和鲁棒性分离的临界峰值对和第一的洗脱峰最大保留。 通过使用网格点搜索方法确定了最优条件。 实验验证确认定义最优条件的充分性。 最后，在优化的色谱条件下该方法的验证，证实了该方法的适用性。

結果 (中文) 3:

In并paper，chromatographic analysis明确active substance olopatadine hydrochloride，which is used in eye drops as antihistaminic、媒介，and其impurity E isomer by hydrophilic interaction liquid chromatography（HILIC）and application明确明确design experiments（DoE）methodology are presented . In addition，benzalkonium chloride is very often used as a preservative in eye drops . Therefore，the evaluation明确其chromatographic behavior in HILIC was carried out as well . In order to estimatechromatographic behavior and组optimal chromatographic conditions，DoE methodology was applied . After the selection明确important chromatographic factors，橙盒–Behnken design was utilized and on the，basis明确the obtained models factor effects were examined . Then，multi - objective robust optimization is performed aiming to obtain chromatographic conditions即comply with several质量criteriasimultaneously : adequate and robust separation明确critical peak pair and maximum retention明确the first eluting peak . The optimal conditions are identified by using grid point search methodology . The experimental verification confirmed the adequacy明确the defined optimal conditions . Finally，under optimal chromatographic conditions，the method was validated and applicability明确the proposed method was confirmed .