A biomimetic potentiometric sensor based on molecularly imprinted polymer for the determination of memantine in tablets Majid Arvand* and Hedyeh Asadi Samie Memantine hydrochloride is one of the first novel class medications for treatment of Alzheimer’s disease. In this work, a biomi- metic potentiometric sensor, based on a non-covalent imprinted polymer, was fabricated for the recognition and determination of memantine in pure drug and tablet pharmaceutical form. The molecularly imprinted polymer was synthesized by precipitation polymerization, using memantine hydrochloride as a template molecule, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linking agent. The sensor was developed by dispersing the memantine imprinted polymer particles in dibutyl sebacate plasticizer and embedding in poly(vinyl chloride) matrix. The wide linear range (10 5 10 1 M), with a near Nernstian response of 57.4 mV/decade, a limit of detection 6.0  10 6 M, fast response time (~15 s) and a satisfactory long- term stability (4 months) are characterizations of the proposed sensor. The sensor showed a high selectivity and a sensitive re- sponse to the template in aqueous system. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode. It was used as indicator electrode in potentiometric determination of memantine in pharmaceutical formulations. Copyright © 2012 John Wiley & Sons, Ltd. Keywords: molecularly imprinted polymer; potentiometric sensor; PVC membrane; memantine hydrochloride; tablets Introduction Molecularly imprinted polymers (MIPs) exhibiting high selectivity and affinity to the predetermined molecule (template) are now see- ing a fast-growing research. [1,2] MIPs are cross-linked polymers with specific binding for a particular analyte. [3,4] These binding sites are tailor made in situ by the copolymerization of functional and cross-linking monomers in the presence of a print molecule called the ‘template’. After polymerization, the removal of template leaves recognition sites that are complementary to the print molecule in terms of size, shape, and functionality. In addition, MIPs unlike bio- logical counterparts are highly stable against mechanical stress, elevated temperatures and high pressures, resistant to harsh envir- onments such as acids, bases and organic solvents. [5] One of many attraction features of the molecular imprinting technique is its appli- cation to a wide range of target molecules such as drugs, herbicides, carbohydrates, amino acids, and other biologically and environmen- tally important molecules. [6] The different strategies of molecular im- printing include (1) ‘covalent’ or ‘pre-organized’, (2) ‘non-covalent’ or ‘self-assembly’, (3) ‘semi-covalent’ or ‘sacrificial spacer’, (4) ‘metal ion’, and (5) ‘metal-chelate’ and have been used in various fields, includ- ing sensors. [5] Among these different methods, the non-covalent ap- proach introduced by Mosbach et al. in 1981 uses only non-covalent interactions between the template and the functional monomers; it is probably the most flexible regarding the selection of the func- tional monomers and the possible template molecules. For these reasons, the non-covalent approach has been the most widely adopted. The possibility of using tailor-made, highly selective, and low-cost arti ficial receptors, with good mechanical, thermal, and chemical properties has paved the way for the development of a new generation of chemical sensors, using imprinted polymers as recognition elements. [7–11] Detection applications are employing transduction mechanisms including conductometry, [12] amperome- try, [13,14] voltammetry, [15,16] quartz microbalance, [17] surface plasmon resonance, [18] and field effect devices. [19] Potentiometric technique is also well-known versatile, simple, rapid, and inexpensive method for determination of target ion (molecule). Potentiometric technique is another approach to elec- trochemical transduction of ion selective sensors based on MIP. The first ion selective electrode based on a templated polymer us- ing a potentiometry method has been reported by Murray et al. [20] showing selectivity to lead ions. For the development of MIP sensors, it is important that the creation of membrane potential between sample and inner filling solutions do not require the template to be extracted from the membrane. [21] Another unique feature of potentiometry is that the species do not have to diffuse through the membrane, so that there is no size restriction on the template compound. Despite all these advantages, only a very few MIP-based sensors have been reported using potentiometric transducer. [16,22–24] Memantine (1-amino-3,5-dimethyladamantane) (Mem) (scheme 1) is a tricyclic amine structurally and pharmacologically related to the antiviral amantadine. The drug is used to treat Parkinson’s disease, movement disorders, and dementia syndrome. Memantine is in a class of medications called N-methyl-D-aspartate (NMDA) receptor antagonists. It works by decreasing abnormal activity in the brain. Memantine can help people with Alzheimer’s disease to think more * Correspondence to: Majid Arvand, Department of Chemistry, Faculty of Science, University of Guilan, PO Box 1914, Rasht, Iran. E-mail: arvand@guilan.ac.ir Department of Chemistry, Faculty of Science, University of Guilan, PO Box 1914, Rasht, Iran Drug Test. Analysis (2012) Copyright © 2012 John Wiley & Sons, Ltd. Research article Drug Testing and Analysis Received: 22 April 2011 Revised: 10 September 2011 Accepted: 11 September 2011 Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/dta.371