一种可持续的、质量源于设计（QbD）启发的同步荧光光谱法用于同时分析COVID-19和过敏性鼻炎联合治疗中的西替利嗪和孟鲁司特

文献信息

中文摘要

开发并验证了一种新型直接同步荧光光谱法，用于同时测定盐酸西替利嗪（CTZ）和孟鲁司特钠（MKT），这两种药物常用于COVID-19联合治疗。孟鲁司特采用一阶导数同步荧光法在422 nm处测定，该波长对应西替利嗪的零交叉点。西替利嗪采用新应用的比率导数同步荧光光谱法（1DD-SFS）技术定量，使用孟鲁司特（0.1 μg/mL）作为除数，允许在293 nm处测量西替利嗪。通过使用十六烷基三甲基溴化铵（CTAB）和硫酸进行胶束增溶，西替利嗪和孟鲁司特的天然荧光显著增强。采用两水平因子设计进行方法优化，最佳条件包括0.5% w/v CTAB和0.2 M硫酸。根据ICH指南进行验证，证明了方法的特异性、灵敏度和稳健性。该方法在MKT 0.1-1.0 μg/mL和CTZ 1.0-10.0 μg/mL范围内表现出线性，检测限分别为0.017和0.415 μg/mL。所开发的方法应用于模拟片剂配方的实验室制备混合物中MKT和CTZ的同时测定。使用Eco-Scale、Complex MoGAPI、AGREE和BAGI评估了绿色度和实用性，确定该方法为环保且适用于常规质量控制。

英文摘要

A novel direct spectrofluorimetric method was developed and validated for simultaneous determination of cetirizine hydrochloride (CTZ) and montelukast sodium (MKT), commonly used in COVID-19 combination therapy. Montelukast was determined using first derivative synchronous fluorescence at 422 nm, corresponding to a zero-crossing point for CTZ. Cetirizine was quantified using a newly applied ratio derivative synchronous fluorescence spectroscopy (1DD-SFS) technique, using MKT (0.1 μg/mL) as a divisor, allowing CTZ measurement at 293 nm. Cetirizine and montelukast native fluorescence was significantly enhanced by micellar solubilization using cetyltrimethylammonium bromide (CTAB) and sulfuric acid. A two-level factorial design was employed for method optimization, with optimal conditions incorporating 0.5% w/v CTAB and 0.2-M sulfuric acid. Validation was performed according to ICH guidelines, proving the methods specificity, sensitivity, and robustness. The methods demonstrated linearity in the range of 0.1-1.0 μg/mL for MKT and 1.0-10.0 μg/mL for CTZ, with detection limits of 0.017 and 0.415 μg/mL, respectively. The developed methods were applied for MKT and CTZ concurrent determination in laboratory-prepared mixtures simulating tablet formulations. Greenness and practicality were assessed using Eco-Scale, the Complex MoGAPI, AGREE, and BAGI establishing the method as eco-friendly and suitable for routine quality control.