A novel, simple and sensitive electrochemical method for the determination of ledipasvir (LED), the newly FDA approved Hepatitis C antiviral drug was developed and validated using ε-MnO2-modified graphite electrode. Two different MnO2 polymorphs (γ- and ε-MnO2 nanoparticles) were synthesized and characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FTIR), energy dispersive X-ray (EDX) and thermogravimetric analysis (TGA). Surface area measurements show that ε-MnO2 NPs have large surface area of 345 m2/g, which is extremely high if compared to that of γ-MnO2 NPs (38 m2/g). In addition, a comprehensive study of the difference in the electrochemical behavior of LED while using pencil graphite electrode (PGE) modified with either γ- or ε-MnO2 NPs is carried out. It was found that surface area and percentage of surface hydroxyls of MnO2 NPs are the key factors governing the sensitivity of the fabricated electrode toward the oxidation of the positively charged LED. Scanning electron microscopy (SEM) was employed to investigate the morphological shape of MnO2 NPs and the surface of the bare and modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used for the surface analysis of the modified electrodes. Based on the obtained results, ε-MnO2/PGE was applied as a selective and sensitive electrode for determination of LED. Under the optimized experimental conditions, ε-MnO2/PGE provides a linear response over the concentration range of 0.025-3.60 μmol L-1 LED with a low limit of detection, which was found to be 5.10 nmol L-1 (4.50 ng mL-1) for the 1st peak and 9.20 nmol L-1 (8.10 ng mL-1) for the 2nd one. In addition, the oxidation behavior of LED is discussed with a full investigation of the oxidized product using FT-IR and LC/MS. The fabricated sensor exhibits a good precision, selectivity and stability and was applied successfully for the determination of LED in its tablets and real rat plasma samples with a good recovery using a simple extraction technique.

中文翻译：

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ε-MnO 2 改性石墨电极作为一种新型电化学传感器，用于超灵敏检测 FDA 新批准的丙型肝炎抗病毒药物 ledipasvir

使用 ε-MnO2 修饰的石墨电极开发并验证了一种新颖、简单且灵敏的电化学方法，用于测定新 FDA 批准的丙型肝炎抗病毒药物 ledipasvir (LED)。合成了两种不同的 MnO2 多晶型物（γ-和 ε-MnO2 纳米颗粒），并使用 X 射线粉末衍射 (XRD)、傅里叶变换红外 (FTIR)、能量色散 X 射线 (EDX) 和热重分析 (TGA) 进行表征。表面积测量表明，ε-MnO2 NPs 具有 345 m2/g 的大表面积，与 γ-MnO2 NPs (38 m2/g) 相比，这是非常高的。此外，还全面研究了使用 γ- 或 ε-MnO2 NPs 改性的铅笔石墨电极 (PGE) 时 LED 电化学行为的差异。结果表明，MnO2 NPs 的表面积和表面羟基百分比是控制所制造电极对带正电 LED 氧化敏感性的关键因素。使用扫描电子显微镜 (SEM) 来研究 MnO2 NPs 的形态以及裸电极和修饰电极的表面。此外，循环伏安法和电化学阻抗谱（EIS）被用于修饰电极的表面分析。基于获得的结果，ε-MnO2/PGE 被用作测定 LED 的选择性和灵敏电极。在优化的实验条件下，ε-MnO2/PGE 在 0.025-3.60 μmol L-1 LED 的浓度范围内提供线性响应，检测下限为 5.10 nmol L-1 (4. 第一个峰为 50 ng mL-1)，第二个峰为 9.20 nmol L-1 (8.10 ng mL-1)。此外，还讨论了 LED 的氧化行为，并使用 FT-IR 和 LC/MS 对氧化产物进行了全面研究。制造的传感器具有良好的精度、选择性和稳定性，并成功应用于测定其片剂和真实大鼠血浆样品中的 LED，使用简单的提取技术具有良好的回收率。