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基于 ZnO 纳米粒子辅助分子印迹聚合物的定制电化学传感器灵敏且选择性测定乌帕替尼。

Sensitive and selective determination of upadacitinib using a custom-designed electrochemical sensor based on ZnO nanoparticle-assisted molecularly imprinted polymer.

机构信息

Department of Analytical Chemistry, Ankara University, Faculty of Pharmacy, Ankara, Türkiye.

Graduate School of Health Sciences, Ankara University, Ankara, Türkiye.

出版信息

Anal Bioanal Chem. 2024 Nov;416(28):6517-6527. doi: 10.1007/s00216-024-05541-0. Epub 2024 Sep 17.

Abstract

Upadacitinib (UPA) is a selective and reversible oral Janus kinase (JAK) 1 inhibitor and is of great importance in treating inflammatory bowel disease (Zheng et al., Int Immunopharmacol 126:111229, 2024; Foy et al., JAAD Case Rep 42:20-22, 2023). Although there are limitations to the effectiveness of UPA, it has received positive responses in clinical trials and is approved for the treatment of atopy dermatitis (AD) (Li et al., Int Immunopharmacol 125:111193, 2023). In this study, a nanoparticle-doped molecularly imprinted polymer (MIP)-based electrochemical sensor was developed for sensitive and selective detection of UPA. The developed sensor was designed as a thin film layer using the photopolymerization method on the surface of the prepared nanoparticle-doped polymerization solution glassy carbon electrode (GCE). Various nanoparticles, such as multi-walled carbon nanotube, titanium dioxide, oxide, and zinc oxide (ZnO) nanoparticles, were the most suitable for UPA. Surface characterization of the developed sensor was done by scanning electron microscopy (SEM), and electrochemical characterization was done by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The quantitative analysis of UPA was performed in 5.0 mM [Fe (CN)] solution using the differential pulse voltammetry (DPV) technique. Under optimum conditions, the calibration range was between 0.1 and 1 pM. The limit of detection (LOD) and limit of quantification (LOQ) were calculated as 0.005 pM and 0.017 pM, respectively. The sensor's accuracy was proven by performing a recovery study in serum. The sensor's selectivity was also evaluated using common interfering substances such as KNO, CaCl, NaSO, uric acid, ascorbic acid, dopamine, and paracetamol. According to the results obtained, the performance of the designed sensor was found to be quite sensitive and selective in determining UPA. The developed UPA-ZnO/3-APBA@MIP-GCE sensor showed high sensitivity and selectivity towards UPA. In addition, the selectivity, the most important feature of the MIP-based sensor, was confirmed by imprinting factor (IF) calculations using tofacitinib (TOF) and ruxolitinib (RUX). The sensor's unique selectivity is demonstrated by its successful performance even in the presence of UPA impurities.

摘要

乌帕替尼(UPA)是一种选择性和可逆的口服 Janus 激酶(JAK)1 抑制剂,在治疗炎症性肠病方面具有重要意义(Zheng 等人,Int Immunopharmacol 126:111229, 2024;Foy 等人,JAAD Case Rep 42:20-22, 2023)。尽管 UPA 的有效性存在一定的局限性,但它在临床试验中得到了积极的反应,并被批准用于治疗特应性皮炎(AD)(Li 等人,Int Immunopharmacol 125:111193, 2023)。在这项研究中,开发了一种基于纳米粒子掺杂分子印迹聚合物(MIP)的电化学传感器,用于灵敏和选择性检测 UPA。所开发的传感器采用光聚合方法设计为薄膜层,在制备的纳米粒子掺杂聚合溶液玻碳电极(GCE)表面上。各种纳米粒子,如多壁碳纳米管、二氧化钛、氧化硅和氧化锌(ZnO)纳米粒子,对 UPA 最适合。通过扫描电子显微镜(SEM)对开发的传感器进行表面特征描述,并通过循环伏安法(CV)和电化学阻抗谱(EIS)进行电化学特征描述。使用差分脉冲伏安法(DPV)技术,在 5.0 mM [Fe(CN)₆]溶液中对 UPA 进行定量分析。在最佳条件下,校准范围在 0.1 和 1 pM 之间。检测限(LOD)和定量限(LOQ)分别计算为 0.005 pM 和 0.017 pM。通过在血清中进行回收研究证明了传感器的准确性。还使用常见的干扰物质,如 KNO、CaCl、NaSO、尿酸、抗坏血酸、多巴胺和对乙酰氨基酚,评估了传感器的选择性。根据获得的结果,发现设计的传感器在确定 UPA 方面表现出相当高的灵敏度和选择性。开发的 UPA-ZnO/3-APBA@MIP-GCE 传感器对 UPA 表现出高灵敏度和选择性。此外,通过使用托法替尼(TOF)和鲁索替尼(RUX)计算印迹因子(IF),确认了基于 MIP 的传感器最重要的特征——选择性。传感器的独特选择性通过其在存在 UPA 杂质的情况下仍能成功表现出来得到证明。

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