Abstract

            Memantine belongs to a novel class of Alzheimer's disease drugs acting by blocking N-methyl-D-aspartate (NMDA) type glutamate receptors recommended for treatment of moderate to severe Alzheimer’s disease.  Currently, there are no official analytical methods available in the pharmacopoeias[1,2].  The analysis of memantine is problematic because of its lack of chromophore or fluorophore.  Several methods for analysis of the drug were reported in the literatures, including liquid chromatography-mass spectrometry (LC-MS)[3], spectrofluorimetry[4], and gas chromatography-mass spectrometry (GC-MS)[5].  Electromigration methods such as capillary electrophoresis (CE) offer benefits in terms of short analysis time, low sample and chemical consumption but they have been investigated only to a limited extent.  The overall aim of this project is to assess and develop new analytical methods for Alzheimer's disease drugs utilising electromigration methods focusing on miniaturised and microfluidic chip-based methods.  In this work, we investigated the available detection options for CE methods.  CE-MS methods involved typically 100 mmol/L ammonium acetate background electrolyte (pH 10) and ESI (5 kV, 10 µL/min) with an ion  trap, yielding limit of detection (LOD) values of 0.04 µg/mL, which corresponds at given sampling volume to 40 ng.  Microchip CE is a miniaturized system equipped with laser induced fluorescence (LIF) detection enabling the high detection sensitivity.  Derivatization of memantine with fluorescent probes is necessary. However, the bulky structure of the drug seems to hinder rapid derivatization processes.  Presently, effects of various derivatizing agents on the reactivity and potential of CE method for memantine analysis is discussed.