Fabrication of water compatible and biodegradable super-paramagnetic molecularly imprinted nanoparticles for selective separation of memantine from human serum prior to its quantification: An efficient and green pathway Fardous A. Mohamed a , Pakinaz Y. Khashaba a,b , Mohamed M. El-Wekil a , Reem Y. Shahin c, ⁎ a Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Assiut University, Egypt b Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Deraya University, El-Minya, Egypt c Drug Research Center, Assiut University, Egypt abstract article info Article history: Received 9 May 2019 Received in revised form 4 August 2019 Accepted 11 August 2019 Available online 12 August 2019 A novel green magnetic molecularly imprinted solid phase extraction (MMI-SPE) for separation of memantine (MEM) from complicated matrices was proposed. The nanomaterial was synthesized via crosslinking of chitosan (CHIT) with [3-(2, 3-epoxypropoxy)-propyl] trimethoxysilane (EPPTMS) in presence of MEM as a template. The nanocomposites, in all steps, were characterized by SEM, FTIR and PXRD techniques. The adsorbed drug was re- moved from magnetic molecular imprinted polymer (MMIP) cavity by ethanol: acetic acid (8:2, v/v) and then, coupled with sodium 1, 2-naphthoquinone-4-sulphonate (NQS) in iodine/alkaline medium to yield highly fluo- rescent product, after reduction with potassium borohydride (KBH 4 ). Variables affecting extraction of MEM from imprinted sites and its fluorometric analysis were studied. The linearity was achieved over concentration range of 1.84–95.0 ng mL -1 with LOD of 0.6 ng mL -1 . The method was successfully applied for determination of MEM in its pharmaceutical tablets and human serum with recoveries of 100.8 ± 3.0, 97.6 ± 2.9, respectively. © 2019 Published by Elsevier B.V. Keywords: Memantine Magnetic molecular imprinted polymer Sodium 1, 2-naphthoquinone 4-sulphonate Fluorimetry Human serum 1. Introduction Major depressive disorder (MDD) is a disabling and chronic disorder with prevalence of 15–20% worldwide. It is one of the main reasons of morbidity and associated with functional and cognitive impairments [1,2]. The first line for treatment of MDD is antidepressant drugs that act through improvement of monoamine at synapses but they have sev- eral limitations such as delay onset of therapeutic action, low rates of re- mission and serious adverse effects [3,4]. Several clinical studies have proved that neurotransmission of glutamate via N-methyl-D-aspartate (NMDA) receptors plays a vital role in depression treatment [5]. In path- ological conditions, excessive activation of NMDA receptors predomi- nant that increases influx of Ca 2+ , leading to neurotoxicity [6,7]. So that the introduction of NMDA receptor antagonists such as MEM alone or in combination with traditional antidepressants, plays a good medication for treatment of MDD and mild to severe Alzheimer's dis- ease [8]. The main problem in analysis of MEM is the absence of chromophore and/or fluorophore that limits its detection. In addition, few methods were developed to analyze MEM including spectrophotometry [9–11], spectrofluorometry [11] and chromatographic methods [12–16]. Spec- troscopic methods deficit selectivity, sensitivity and have not been ap- plied in biological fluids. On the other hand, chromatographic methods, although may have sufficient sensitivity and selectivity, but need exhaustive preparation steps, large solvent consumption and ex- pensive instrumentation. The aim of this work is to: (i) separate MEM from complicated matrices via magnetic molecular imprinted solid phase extraction (MMI-SPE) and, (ii) develop a sensitive fluorometric method for detection of MEM in human serum prior to MMI-SPE. The MMI-SPE involved polymerization of chitosan (CHIT) on magnetic nanoparticles with [3-(2, 3-epoxypropoxy)-propyl] trimethoxysilane (EPPTMS) in presence of MEM as a template and, subsequent removal of MEM from molecular imprinted polymer (MIP), leaving behind imprinted cavities which are complementary in size, shape and func- tionality to MEM. The fluorometric analysis was carried out using deriv- atization with sodium 1, 2-naphthoquinone-4-sulphonate and the removed MEM. Then, the product was reduced with potassium borohy- dride (KBH 4 ) to yield highly fluorescent product measured at λ em. = 450 nm after λ exc. = 345 nm. MMI-SPE increases the selectivity and de- rivatization of the removed MEM improves the sensitivity of the fluo- rometric detection of MEM. Molecular imprinted polymers (MIPs) are promising selective sor- bent toward analyte extraction prior to its determination. Moreover, International Journal of Biological Macromolecules 140 (2019) 140–148 ⁎ Corresponding author. E-mail address: reemshain19@yahoo.com (R.Y. Shahin). https://doi.org/10.1016/j.ijbiomac.2019.08.099 0141-8130/© 2019 Published by Elsevier B.V. Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: http://www.elsevier.com/locate/ijbiomac