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All-electrochemical nanocomposite two-electrode setup for quantification of drugs and study their electrocatalytical conversion by cytochromes P450
Electrochimica Acta ( IF 5.5 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.electacta.2019.135579
Victoria V. Shumyantseva , Tatiana V. Bulko , Alexey V. Kuzikov , Rami A. Masamrekh , Apollinariya Yu Konyakhina , Iuliia Romanenko , Johannes B. Max , Moritz Köhler , Andrei A. Gilep , Sergey A. Usanov , Dmitry V. Pergushov , Felix H. Schacher , Larisa V. Sigolaeva

This paper describes electrochemical behavior and an electrooxidative method for the determination of diclofenac, DF, (2-[(2,6-dichlorophenyl)amino]benzene-acetic acid) and acetaminophen, AC, (N-acetyl-p-aminophenol). Drugs electrochemical oxidation was realized on the surface of graphite-based screen printed electrodes (SPE) modified with a stable dispersion of multiwalled carbon nanotubes (MWCNTs) in aqueous solutions of an amphiphilic poly(1,2-butadiene)-block-poly(2-(N,N-dimethylamino)ethyl methacrylate) diblock copolymer (PB-b-PDMAEMA). The oxidation peak potentials of DF and AC were detected at + 0.53 ± 0.02 V and 0.35 ± 0.02 V (vs. Ag/AgCl), respectively. The analytical characteristics of electro-oxidation of the drugs on the SPE/(PB290-b-PDMAEMA240/MWCNT) constructs were estimated with a detection limit of 35 nM and 40 nM, and a sensitivity of 4.90 mA/mol and 2.3 mA/mol for DF and AC, respectively. Electro-oxidation of DF and AC was applied as analytical technique for the detection of theses pharmaceuticals in their mixtures and in human serum. Further, we demonstrate an approach for the estimation of the enzymatic activity of cytochrome P450 3A4 (CYP3A4) based on the electrochemical oxidation of residual DF used as a model drug. Two separate electrochemical cell were used each was supplied by specified electrode. The first one was CYP-sensitive electrode, which contains CYP3A4 immobilized on didodecyldimethylammonium bromide (DDAB) as a CYP3A4 fixing matrix, while another one was newly developed drug-sensitive electrode. Therefore, drug conversion, which takes place in the first electrochemical cell supplied by CYP-sensitive electrode, can be quantitatively monitored by drug-sensitive electrode by taking aliquots at specified time periods and assaying a residual drug concentration in the second electrochemical cell. Thus, the estimation of kinetic parameters for CYP3A4 catalysis can be carried out.



中文翻译:

全电化学纳米复合两电极设置,用于定量药物并研究其通过细胞色素P450的电催化转化

本文介绍了测定双氯芬酸DF(2-[((2,6-二氯苯基)氨基]苯乙酸)和对乙酰氨基酚AC(N-乙酰基-氨基苯酚)的电化学行为和电氧化方法。药物电化学氧化用多壁碳纳米管(MWCNT)中的两亲性的聚(1,2-丁二烯)的水溶液的稳定分散体改性石墨系丝网印刷电极(SPE)的表面上实现-嵌段-聚(2- -(N,N-甲基丙烯酸N,N-二甲氨基)乙酯)二嵌段共聚物(PB- b-PDMAEMA)。DF和AC的氧化峰电位分别在+ 0.53±0.02 V和0.35±0.02 V(vs。Ag / AgCl)下检测。药物在SPE /(PB 290 - b -PDMAEMA 240上的电氧化分析特性(MWCNT)构建物的检出限估计为35 nM和40 nM,对DF和AC的灵敏度分别为4.90 mA / mol和2.3 mA / mol。DF和AC的电氧化被用作分析技术,以检测这些药物在混合物中和在人血清中的含量。此外,我们展示了一种基于作为模型药物的残留DF的电化学氧化来估算细胞色素P450 3A4(CYP3A4)酶活性的方法。使用两个分开的电化学电池,每个由指定电极供电。第一个是CYP敏感电极,其中包含固定在十二烷基二甲基溴化铵(DDAB)上的CYP3A4作为CYP3A4固定基质,而另一个是新开发的药物敏感电极。因此,药物转换 CYP敏感电极提供的第一个电化学电池中发生的“ H2O3”可以通过在指定时间段取等分试样并测定第二个电化学电池中的药物残留浓度来通过药物敏感电极进行定量监测。因此,可以进行CYP3A4催化动力学参数的估计。

更新日期:2020-01-14
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