A Stability-Indicating HPLC Method for the Determination of Memantine Hydrochloride in Dosage Forms through Derivatization with 1-Fluoro-2,4-dinitrobenzene.

Hassan Jalalizadeh

doi:10.3797/scipharm.1310-09

Abstract

Memantine is chemically a tricyclic amine and is used for Parkinson’s disease and movement disorders. Although several HPLC methods with different derivatization reagents have been developed for the determination of memantine in biological fluids, there are some complications which limit the use of these methods in routine analysis of memantine in in vitro tests. We established a simple, sensitive, precise, and accurate HPLC method for the quantification of memantine in dosage forms. Pre-column derivatization of memantine was performed with 1-fluoro-2,4-dinitrobenzene and the reaction product was separated on a Nova-Pak C18 column. A mixture of acetonitrile and sodium dihydrogenphosphate (pH 2.5; 0.05 M) (70: 30, v/v) was used as the mobile phase. UV detection was performed at 360 nm. Forced degradation studies were performed on a powdered tablet sample of memantine hydro-chloride using acidic (0.1 M hydrochloric acid), basic (0.1 M sodium hydroxide), oxidative (10% hydrogen peroxide), thermal (105°C), photolytic, and humidity conditions. Good linearity (r2=0.999) was obtained over the range of 1–12 μg mL−1 of memantine hydrochloride with acceptable within-day and between-day precision values in the range of 0.05–0.95%. The proposed method was used for the assay determination and dissolution rate study of memantine dosage forms with excellent specificity.

Highlights

Memantine hydrochloride, 1-amino-3,5-dimethyladamantane hydrochloride (Figure 1), is chemically a tricyclic amine and is pharmacologically related to the antiviral prototype amantadine and its α-methyl derivative, rimantadine
Several HPLC methods with different derivatization reagents have been developed for the determination of memantine in biological fluids, there are some complications which limit the use of these methods in routine analysis of memantine in in vitro tests
Studies requiring the quantitation of memantine in plasma, cerebrospinal fluid, urine, and other tissues have used gas chromatographic-mass spectrometric (GC-MS) [4], liquid chromatography-tandem mass spectrometry [5-9], and HPLC methods in combination with ultraviolet detection or fluorescence detection using different derivatizing reagents [10–17]

Summary

Introduction

1-amino-3,5-dimethyladamantane hydrochloride (Figure 1), is chemically a tricyclic amine and is pharmacologically related to the antiviral prototype amantadine and its α-methyl derivative, rimantadine. Memantine and rimantadine have been approved in the U.S for the prophylaxis and treatment of influenza. Amantadine and memantine are used for the treatment of Parkinson's disease and movement disorders [1]. Memantine is approved for the treatment of moderate-to-severe Alzheimer's disease [2], and has received a limited recommendation by the UK's National Institute for Clinical Excellence for patients who fail with other medicinal therapeutic options [3]. Memantine has no significant ultraviolet, visible, or fluorescence absorption. Studies requiring the quantitation of memantine in plasma, cerebrospinal fluid, urine, and other tissues have used gas chromatographic-mass spectrometric (GC-MS) [4], liquid chromatography-tandem mass spectrometry [5-9], and HPLC methods in combination with ultraviolet detection or fluorescence detection using different derivatizing reagents [10–17]. The reaction time for the derivatization of memantine and 4-fluoro-7-nitro-2,1,3-benzoxadiazole is not too long (about 5 min), but the total run time of the HPLC method is about 40 min [12]

Objectives

Results

Conclusion