The first spectrofluorimetric-based approach for studying stability-indicating assay and quantifying midodrine in its bulk powder, prescribed matrices; application to content homogeneity testing and sustainability evaluation

Abstract

A novel application of a spectrofluorimetric method has been developed and validated for the stability analysis and quantification of midodrine hydrochloride in tablets and crude form. This study describes a technique based on the selective derivatization of midodrine’s (MDN) primary amine group with NBD-Cl reagent under a borate buffer system (pH 8.5), yielding a highly fluorescent benzofurazan derivative. The product was measured at λ_ex = 462 nm and λ_em = 537 nm, demonstrating a linear range of 30–600 ng/mL (r = 0.9998). The method’s detection (8.9 ng/mL) and quantitation (26.98 ng/mL) limits were determined. Validation followed ICH guidelines, confirming precision, accuracy (recovery: 98.9–100.7 %), and absence of excipient interference in commercial formulations (tablets and oral drops). The method was applied to assess stress-induced degradation (acid, alkali, oxidation, aqueous, and photolytic conditions) and determine degradation kinetics under each condition. Additionally, content uniformity analysis of tablets was performed per USP guidelines, demonstrating robustness for quality control applications.