Fabrication of a Sensitive and Straightforward Electrochemical Sensor Utilizing Molecularly Imprinted Polymers for the Targeted Detection of the Antiretroviral Drug Ritonavir

This study developed a new sensor technology utilizing molecularly imprinted polymers (MIPs) for the electrochemical detection of ritonavir (RTV), a protease inhibitor for HIV treatment. Since RTV is also a major inhibitor of the P450 3A4 isoenzyme, it is often given with other medications. Hence, assessing the therapeutic effectiveness of RTV requires precise measurement of RTV in complicated biological matrices and complex mixtures. On the surface of the glassy carbon electrode (GCE), a polymeric layer was created utilizing RTV as the template molecule, methacrylic acid (MAA) as the functional monomer, and aniline in phosphate buffer (pH 7). The morphological and electrochemical properties of the RTV/ANI-co-MAA@MIP-GCE sensor were evaluated through scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The sensor demonstrated a linear detection range for RTV using a redox probe (5.0 mM [Fe(CN) ₆ ^]−3/−4 ) between 1.0 × 10 ^− 12 M and 1.5 × 10 ^− 11 M, with a limit of detection (LOD) and limit of quantification (LOQ) for standard solutions determined to be 2.75 × 10 ^− 13 M and 9.18 × 10 ^− 13 M, respectively. The sensor was then successfully used to identify RTV in commercial serum samples and tablets, producing acceptable recovery results. Consequently, the RTV/ANI-co-MAA@MIP-GCE exhibited high specificity, accuracy, and sensitivity for detecting RTV. Density functional theory (DFT) calculations were performed to complement the experimental findings to explore the interactions between the template and monomer, revealing binding energies for RTV–MAA complexes at various template: monomer ratios and elucidating potential intermolecular interactions.