A Sustainable, Quality-by-Design (QbD) Inspired Spectrofluorimetric Method for the Concurrent Analysis of Cetirizine and Montelukast in COVID-19 and Allergic Rhinitis Combination Therapy.

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.