Contents lists available at ScienceDirect Microchemical Journal journal homepage: www.elsevier.com/locate/microc Hetero nanostructured iron oxide and bentonite clay composite assembly for the determination of an antiviral drug acyclovir Nagaraj P. Shetti a,d, , Shweta J. Malode a , Deepti S. Nayak a , Revati R. Naik b , Girish T. Kuchinad b , Kakarla R. Reddy c , Shyam S. Shukla d , Tejraj M. Aminabhavi d a Center of Electrochemical Science and Materials, Department of Chemistry, K.L.E. Institute of Technology, Affiliated to Visvesvaraya Technological University, Gokul, Hubballi 580030, Karnataka, India b Department of Chemistry, Dr. A.V. Baliga College of Arts and Science, Kumta, North Canara 581343, Karnataka, India c School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, NSW 2006, Australia d Department of Chemistry and Biochemistry, Lamar University, Beaumont, TX 77710, United States of America ARTICLE INFO Keywords: Composite sensor Antiviral drug Difusion-controlled Electrochemical process Clinical analysis ABSTRACT Fabrication of chemically modifed electrodes for a variety of applications has gained much interest in sensor applications. In search of new materials, carbon paste electrodes (CPEs) loaded with one or more nanoparticles have shown good results for the trace detection of molecules. In this research, a blend of bentonite clay particles and γ-Fe 2 O 3 nanoparticles were employed as a modifer in CPE for the quantifcation of acyclovir (ACV), an antiviral agent. The sensor demonstrated a quantitative assessment of acyclovir with the limit of detection (LOD) value of 1.5 nM. The sensor had good reproducibility, the stability of signal response, and high selectivity for the electrochemical analysis of ACV in pharmaceutical formulations and spiked human urine samples. The results also revealed a sensitive performance of the sensor in pharmacokinetic studies, quality control, and clinical research. 1. Introduction Over the past decades, several infectious diseases have threatened the human and animal life as these diseases have been the leading cause of death among other diseases [1]. Among the many organic molecules, purines and their derivatives are known to exhibit antiviral activities. Acyclovir (ACV) (Fig. S1) belongs to the synthetically prepared purine- based nucleoside analogue, which acts as a pivotal agent widely used in antiviral therapy [2]. ACV has been widely used in the clinical treat- ment of hepatitis B virus (HBV), epstein-barr virus, herpes simplex virus (HSV), and varicella zoster virus (VZV), since it ofers astonishing therapeutic proft in treating the viral diseases that are similar to ker- atitis, encephalitis, cold sores, central nervous system infections, and corneal blindness [3]. In the treatment of chickenpox and shingles, intravenous or oral administration of ACV is preferred [4]. In im- munologically compromised patients, the prophylaxis of cytomegalo- virus infections can be achieved by the potential efect of ACV [5]. However, higher consumption of ACV is known to induce adverse ef- fects such as nephrotoxicity, neurotoxicity, phlebophlogosis, cepha- lalgia, urticaria, emesis and diarrhea [6–9]. Further, ACV is a widely preferred drug due to its low cytotoxicity and high selectivity to infected cells region. Therefore, ACV determination in pharmaceuticals and biological fuids is important in clinical studies. In the literature, various analytical methods including fow injec- tion-chemiluminiscence [10], high-performance capillary electrophor- esis (HPCE) [11], radioimmunoassay (RIA) [12,13] high performance liquid chromatography (HPLC) [14–17], electrochemiluminescence method [18], thin layer chromatography (TLC) [19–21], micellar electro-kinetic chromatography [22], and analytical techniques [23–34] have been accounted for the analysis of ACV and its associated analogues. The reported conventional methods such as automated high per- formance liquid chromatography (HPLC), fuorescence and spectro- fuorimetry showed the limit of detection (LOD) values as 5300 nM, 130 nM, and 44.0 nM [14–16]. Even though the above methods have been widely accepted, but they are occasionally agonized from the elaborated sample preparation, costly equipments, long analysis time, and specialized expertise. On the other hand, electrochemical methods can overcome some of the problems faced by the conventional methods in the quantifcation of molecules due to ease of sample preparation, moderate equipment facility, quick response time, and accuracy. In this pursuit, few electrochemical methods have been explicated the https://doi.org/10.1016/j.microc.2020.104727 Received 24 October 2019; Received in revised form 6 February 2020; Accepted 9 February 2020 Corresponding author. E-mail address: npshetti@kleit.ac.in (N.P. Shetti). Microchemical Journal 155 (2020) 104727 Available online 14 February 2020 0026-265X/ © 2020 Elsevier B.V. All rights reserved. T