Validation and application of a simple reverse phase HPLC method for in vitro dissolution studies of memantine hydrochloride tablet

Abstract

A simple, accurate and cost-effective ultraviolet-high performance liquid chromatography (UV-HPLC) assay method was developed and validated for the determination of derivatized memantine, a representative oral noncompetitive N-methyl-d-aspartate receptor antagonist to treat Alzheimer’s disease, in dissolution medium. Optimized derivatization process of memantine was performed with 9-fluorenylmethyl-chloroformate (FMOC), and injected with the UV-HPLC system for quantitation. Derivatized memantine were separated on a reverse phase C18 column (Shiseido, 250 × 4.6 mm, 5 μm) with a mixture of 50 mM phosphate buffer (pH 4, adjusted with orthophosphoric acid) and Acetonitrile (20:80, v/v), at a flow rate of 2.0 mL/min. UV detection was monitored at 265 nm. The detector response was specific and linear over the concentration range of 1.0–20.0 μg/mL. Validation parameters of derivatized memantine with the sensitivity, selectivity, linearity, accuracy, precision and stability in dissolution medium (pH 1.2) were acceptable based on International Conference on Harmonization Q2 (R1). The assay method validated in this work was successfully applied for a dissolution study of a commercial tablet containing memantine hydrochloride (i.e., Ebixa®, 10 mg). Thus, the developed method would be appropriate for routine in vitro dissolution studies of memantine hydrochloride tablet.