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一种使用分子印迹聚合物的电化学传感器的开发,用于抗逆转录病毒药物利托那韦的特异性测定。

Development of an electrochemical sensor using molecularly imprinted polymers for the specific determination of the antiretroviral drug ritonavir.

作者信息

Faysal Abdullah Al, Cetinkaya Ahmet, Erdoğan Taner, Ozkan Sibel A, Gölcü Ayşegül

机构信息

Department of Chemistry, Faculty of Sciences and Letters, Istanbul Technical University, Maslak, Istanbul, Turkey.

Department of Analytical Chemistry, Gülhane Faculty of Pharmacy, University of Health Sciences, Ankara, Turkey.

出版信息

Mikrochim Acta. 2025 Aug 6;192(9):560. doi: 10.1007/s00604-025-07427-z.

DOI:10.1007/s00604-025-07427-z
PMID:40768086
Abstract

An innovative sensor technology is introduced that employs molecularly imprinted polymers (MIPs) for the electrochemical detection of ritonavir (RTV), a protease inhibitor utilized in HIV therapy. RTV is frequently used in combination with other drugs since it is also a significant inhibitor of the P450 3A4 isoenzyme. Therefore, accurate detection of RTV in complex mixtures and intricate biological matrices is necessary to evaluate the therapeutic efficacy of RTV. A polymeric layer was formed on the surface of the glassy carbon electrode (GCE) using RTV as the template molecule, methacrylic acid (MAA) as the functional monomer, and aniline in a phosphate buffer at pH 7. The morphological and electrochemical characteristics of the RTV/ANI-co-MAA@MIP-GCE sensor were assessed through scanning electron microscopy, Fourier transform infrared spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The sensor exhibited a linear detection range for RTV utilizing a redox probe (5.0 mM [Fe(CN)]) spanning from 1.0 × 10 to 1.5 × 10 M, with the limit of detection and limit of quantification for standard solutions established at 2.75 × 10 M and 9.18 × 10 M, respectively. Subsequently, the sensor was effectively employed to detect RTV in commercial serum samples and tablets, yielding satisfactory recovery results. As a result, the RTV/ANI-co-MAA@MIP-GCE demonstrated high specificity, accuracy, and sensitivity in the detection of RTV. Additionally, density functional theory calculations were conducted to support the experimental results, investigating the interactions between the template and monomer, which revealed binding energies for RTV-MAA complexes at different template: monomer ratios and clarified potential intermolecular interactions.

摘要

介绍了一种创新的传感器技术,该技术采用分子印迹聚合物(MIP)对利托那韦(RTV)进行电化学检测,利托那韦是一种用于HIV治疗的蛋白酶抑制剂。由于RTV也是P450 3A4同工酶的重要抑制剂,因此它经常与其他药物联合使用。因此,准确检测复杂混合物和复杂生物基质中的RTV对于评估RTV的治疗效果至关重要。以RTV为模板分子,甲基丙烯酸(MAA)为功能单体,在pH值为7的磷酸盐缓冲液中加入苯胺,在玻碳电极(GCE)表面形成聚合物层。通过扫描电子显微镜、傅里叶变换红外光谱、循环伏安法和电化学阻抗谱对RTV/ANI-co-MAA@MIP-GCE传感器的形态和电化学特性进行了评估。该传感器利用氧化还原探针(5.0 mM [Fe(CN)])对RTV的线性检测范围为1.0×10至1.5×10 M,标准溶液的检测限和定量限分别为2.75×10 M和9.18×10 M。随后,该传感器有效地用于检测商业血清样品和片剂中的RTV,回收率结果令人满意。结果表明,RTV/ANI-co-MAA@MIP-GCE在检测RTV时具有高特异性、准确性和灵敏度。此外,还进行了密度泛函理论计算以支持实验结果,研究模板与单体之间的相互作用,揭示了不同模板:单体比例下RTV-MAA配合物的结合能,并阐明了潜在的分子间相互作用。

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本文引用的文献

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Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir in Treating HCV Genotypes 1 and 4 in Patients with Advanced Chronic Kidney Disease.奥比他韦/帕立普韦/利托那韦联合达沙布韦治疗晚期慢性肾脏病患者丙型肝炎病毒1型和4型的疗效与安全性
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Oral Nirmatrelvir-Ritonavir as Postexposure Prophylaxis for Covid-19.奈玛特韦/利托那韦口服作为新冠病毒暴露后预防。
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电化学合成 MIP 传感器:在医疗保健诊断中的应用。
Biosensors (Basel). 2024 Jan 30;14(2):71. doi: 10.3390/bios14020071.
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Higher sensitive selective spectrofluorometric determination of ritonavir in the presence of nirmatrelvir: application to new FDA approved co-packaged COVID-19 pharmaceutical dosage and spiked human plasma.在奈玛特韦存在下对利托那韦进行更高灵敏度的选择性荧光光谱测定:应用于美国食品药品监督管理局新批准的新冠病毒联合包装药物剂型及加标人血浆
BMC Chem. 2023 Sep 21;17(1):120. doi: 10.1186/s13065-023-01030-0.
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Electrochemical sensor based on molecularly imprinted copolymer for selective and simultaneous determination of riboflavin, dopamine, and L-tryptophan.基于分子印迹共聚物的电化学传感器用于核黄素、多巴胺和 L-色氨酸的选择性和同时测定。
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Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?帕克洛维德(奈玛特韦/利托那韦):新冠治疗的新方法?
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The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?利托那韦对 CYP3A4 的基于机制的抑制作用:哪种机制?
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A new method for electrochemical determination of Hippuric acid based on molecularly imprinted copolymer.基于分子印迹聚合物的电化学测定马尿酸的新方法。
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