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

ABSTRACT

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 ( ¹ DD‐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.