Sars-cov-2 (COVİD-19) tedavisinde kullanılan antiviral ilaçların seçici ve duyarlı sensörlerle tayini

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Thesis Type: Doctorate

Institution Of The Thesis: Ankara University, Sağlık Bilimleri Enstitüsü, ANALİTİK KİMYA ANABİLİM DALI, Turkey

Approval Date: 2023

Thesis Language: Turkish

Student: AHMET ÇETİNKAYA

Supervisor: Sibel Ayşıl Özkan

Open Archive Collection: AVESIS Open Access Collection

Abstract:

Within the scope of my doctoral thesis, molecularly imprinted polymer (MIP) based sensors were developed for the selective and sensitive analysis of the antiviral drugs ribavirin (RIB), molnupiravir (MOL), umifenovir (UMI), and camostat mesylate (CAM). Electrochemical and surface characterizations of the developed sensors were evaluated using cyclic voltammetry (DV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and contact angle methods. For the detection of RIB, MIP-based electrochemical sensors were developed for the first time using different functional monomers such as pyrrole-para aminophenyl boronic acid (Py-p-APBA) and uracil methacrylate (UraM) in electropolymerization (EP) and photopolymerization (PP) techniques, respectively. Analytical performances of poly(Py-co-p-APBA)/RIB@MIP/GCE and UraM/RIB@MIP/GCE sensors were evaluated using differential pulse voltammetry (DPV). The developed sensors have excellent selectivity with a high imprintig factor (IF) against RIB. For the electrochemical analysis of MOL, MIP-based sensors were prepared by using pyrrole-3-thionyl boronic acid (Py-3-TBA) and guanine methacrylate (GuaM) as monomers in the EP and PP methods, respectively. The limit of detection (LOD) values of the developed poly(Py-co-3-TBA)]/MOL@MIP/GCE and GuaM/MOL@MIP/GCE sensors were calculated as 6.01x10-13 M and 1.13x10-13 M, respectively. The good recovery values obtained in pharmaceutical forms and commercial serum samples showed that the sensors were successfully applied to these samples. For the selective and sensitive analysis of UMI, a MIP-based electrochemical sensor was prepared using butyl methacrylate (BuMA) as a functional monomer and boron nitride (B3N3) to form a porous structure. The developed sensor has been successfully applied to the analysis of UMI using different electroanalytical methods such as DPV and EIS. LOD values indicating the high sensitivity of the UMI@B3N3/BuMA@MIP/GCE sensor were calculated as 4.82x10-14 M and 2.34x10-14 M for the DPV and EIS methods, respectively. Interference and IF analysis confirmed the high selectivity of the developed sensors. For more sensitive and selective analysis of CAM, both MIP-based sensor and dummy imprinted polymer (DIP)-based sensors were prepared using screen printed gold electrodes (SPAuE). Considering the performances of the developed sensors, very effective results were obtained for the poly(Py-co-p-ABA)@CAM@MIP/SPAuE sensor in terms of both analytical validation parameters and applicability compared to DIP sensors prepared with other active compounds. Consequently, MIP-based sensors developed for the electrochemical analysis of RIB, MOL, UMI, and CAM have proven to be more advantageous and alternative methods compared to existing methods. Keywords: Ribavirin, Molnupiravir, Umifenovir, Camostat mesylate, Electrochemical sensor, Molecularly imprinted polymers