Abstract

Objective: Three simple, sensitive, accurate, and precise spectrophotometric methods have been developed and validated for the determination of Alzheimer’s disease drug memantine HCl (MEM) in pure form and pharmaceutical formulations. Methods: The method was based on the formation of charge transfer complex between MEM as n-electron donor and various π-acceptors quinalizarin (Quinz) in methanol, p-chloranilic acid (p-CA) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) in acetonitrile as chromogenic reagents which showed an absorption maximum at 558, 532 and 840 nm using Quinz, p-CA and TCNQ, respectively. The optimization of the reaction conditions such as the type of solvent, reagent concentration and reaction time were investigated. Results: Under the optimum conditions, beer’s law is obeyed in the concentration ranges 4.0–24, 10–160 and 5.0–50 μg/mlusing Quinz, p-CA and TCNQ, respectively with good correlation coefficient (r2 ≥ 0.9995) and with a relative standard deviation (RSD% ≤ 1.11). For more accurate analysis, Ringbom optimum concentration ranges were found to be between 8.0–20, 15–140 and 10–45 μg/ml using Quinz, p-CA and TCNQ, respectively. The limits of detection were found to be 1.2, 2.70 and 1.45 µg/ml and the limits of quantification were found to be 4.0, 9.0 and 4.83 µg/ml for Quinz, p-CA and TCNQ, respectively. A Job's plot of the absorbance versus the molar ratio of MEM to each of the acceptors under consideration indicated (1:1) ratio. Conclusion: The methods were successfully applied to the determination of MEM in its pharmaceutical formulations and the validity assessed by applying the standard addition technique. Results obtained by the proposed methods for the pure MEM and commercial tablets agreed well with those obtained by the reported method.

Highlights

  • Memantine hydrochloride (MEM), chemically known as 1-amino3,5-dimethyladamantane hydrochloride, is an adamantane derivative with a unique non-planar tricyclic saturated ring structure

  • Several methods for analysing memantine HCl (MEM) in pure drugs, pharmaceutical dosage forms, and biological samples have been described in the literature, including high performance liquid chromatography [3-5], liquid chromatography coupled with fluorescence detection [5-9] and mass spectrometry [10-13], gas chromatography with mass spectrometry (GC-MS) [14], potentiometry [15, 16], and spectrofluorimetric [17, 18]

  • The dissociation of the (D–A) complex was promoted by the high ionizing power of the polar solvent and the resulting peaks in the absorption spectra of MEM-acceptor reaction mixtures were similar to the maxima of the radical anions of the acceptors (Quinz., p-chloranilic acid (p-CA).and TCNQ.-) obtained by the iodide reduction method [39]

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Summary

Introduction

Memantine hydrochloride (MEM), chemically known as 1-amino3,5-dimethyladamantane hydrochloride, is an adamantane derivative with a unique non-planar tricyclic saturated ring structure (fig. 1). Memantine is an amantadine derivative and antagonist of N-methyl-D-aspartate (NMDA) receptors. Several methods for analysing MEM in pure drugs, pharmaceutical dosage forms, and biological samples have been described in the literature, including high performance liquid chromatography [3-5], liquid chromatography coupled with fluorescence detection [5-9] and mass spectrometry [10-13], gas chromatography with mass spectrometry (GC-MS) [14], potentiometry [15, 16], and spectrofluorimetric [17, 18]. These procedures, on the other hand, are costly, difficult to use for routine analysis, time consuming, and not available in most laboratories

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