盐酸奥洛他定鼻喷雾剂有关物质的绿色液相色谱测定法，通过设计专家进行稳健性研究。
Green Liquid Chromatography Method for the Determination of Related Substances Present in Olopatadine HCl Nasal Spray Formulation, Robustness by Design Expert.
机构信息
Shenzhen DEC Pharmaceutical Co., Ltd, Analytical Development Department, Shenzhen, China.
GITAM Deemed to be University, Department of Chemistry, School of Science, Hyderabad, Telangana 502329, India.
出版信息
J AOAC Int. 2022 Sep 6;105(5):1247-1257. doi: 10.1093/jaoacint/qsac072.
BACKGROUND
Dual therapeutic nature drug mast cell stabilizer and histamine receptor antagonist olopatadine hydrochloride (OPT) nasal spray does not have an official monograph, and no literature is available. Eye drops formulation had the official monograph for impurities, but the determination was done in two methods.
OBJECTIVE
A simple and effective green liquid chromatography method to develop and validate for the related substances of OPT nasal spray formulation.
METHOD
A 25 min gradient method was employed to separate impurities and OPT with a 1.0 mL/min flow rate using a Boston green C8 (150 mm × 4.6 mm, 5 µm) HPLC column. The set wavelength and column oven temperatures were 299 nm and 30°C, respectively. pH 3.5 phosphate buffer-acetonitrile in the ratio of (70:30, v/v) as mobile phase A and (50:50, v/v) ratio as mobile phase B. A Quality by Design (QbD) based Design of Experiments (DoE) was employed to evaluate the robustness characteristics of the analytical method validation.
RESULTS
The obtained RSD from the precision and intermediate precision was 0.4 to 4.1%. The % recovery of the impurities from LOQ to 150% of specification level was 87.5 to 110.3%. The linear regression curves for the impurities with a correlation coefficient of >0.999 indicate that all peak responses are linear with the concentration. The sample and standard solutions were stable for 24 h at benchtop and refrigerator conditions.
CONCLUSIONS
All the critical peaks were well separated from the forced degradation studies' diluent, placebo, and generated degradation peaks. The method validation data and QbD based robustness study results indicate that the developed impurities method fits the routine quality control laboratory use. National Environmental Index (NMEI), Green Analytical Procedure Index (GAPI), Analytical Eco-scale and Analytical Greenness (AGREE) tools expressed the method's greenness.
HIGHLIGHTS
The proposed method is QbD utilized and green chemistry assessed impurities determination method for OPT in nasal spray formulation.
背景
双重治疗特性药物肥大细胞稳定剂和组胺受体拮抗剂盐酸奥洛他定（OPT）鼻喷雾剂没有官方专论，也没有相关文献。滴眼液制剂有官方专论杂质，但测定是用两种方法进行的。
目的
开发并验证一种简单有效的绿色高效液相色谱法，用于测定 OPT 鼻喷雾剂制剂的有关物质。
方法
采用 25 分钟梯度法，以 1.0ml/min 的流速，用 Boston green C8（150mm×4.6mm，5μm）HPLC 柱分离杂质和 OPT。设定波长和柱温箱温度分别为 299nm 和 30°C。pH 3.5 磷酸盐缓冲液-乙腈的比例为（70:30，v/v）为流动相 A，（50:50，v/v）为流动相 B。采用基于质量源于设计（QbD）的实验设计（DoE）来评估分析方法验证的稳健性特征。
结果
精密度和中间精密度的 RSD 为 0.4%至 4.1%。杂质从 LOQ 到 150%规格水平的回收率为 87.5%至 110.3%。杂质的线性回归曲线相关系数>0.999，表明所有峰响应均与浓度呈线性关系。在室温条件下，样品和标准溶液在 24 小时内稳定。
结论
所有关键峰均与强制降解研究的稀释剂、安慰剂和产生的降解峰很好地分离。方法验证数据和基于 QbD 的稳健性研究结果表明，所开发的杂质方法符合常规质量控制实验室的使用要求。国家环境指数（NMEI）、绿色分析程序指数（GAPI）、分析生态规模和分析绿色度（AGREE）工具表示该方法具有绿色性。
重点
该方法是基于质量源于设计（QbD）的，并评估了用于 OPT 鼻喷雾剂制剂中杂质的绿色化学测定方法。
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