Factorial analysis optimization of memantine hydrochloride spectrofluorimetric quantitation via derivatization with o-phthalaldehyde in the absence of thiol

Abstract

Memantine hydrochloride, low-to-moderate affinity noncompetitive N-methyl-D-aspartate receptor antagonist, is used in the treatment of patients with moderate to severe Alzheimer’s disease. Chemically, Memantine is an aliphatic tricyclic primary amine compound which lacks any UV or fluorescence properties. Previous studies have reported the spectrophotometric quantification of memantine after derivatization reactions with different reagents. In this paper, we reported the formation of a fluorescent product by reacting memantine hydrochloride and o-phthalaldehyde in the absence of a thiol. Experimental design methodologies were used in the optimization step. The variables under investigation were: pH; the ratio between memantine hydrochloride: o-phthalaldehyde and heating time. The results of statistical analysis of two sequential full factorial design were used for quantification of memantine hydrochloride at optimized reaction condition. Optimal conditions for derivatization were: aqueous NaOH, pH 12.2, memantine hydrochloride:o-phthalaldehyde ratio of 1:5, and heating at 70^oC for 45 min. A new eco-friendly spectrofluorimetric derivatization procedure has been developed and validated for analysis of memantine hydrochloride. The linear range was 0.25–10 µg/mL with a quantification limit of 1.97 µg/mL, detection limit of 0.65 µg/mLwith maximum fluorescence intensity development at λex 350 nm and λem 427 nm