Electrochemical Sensor Based On Nano-porous Materials For The Detection Of Hepatotoxic Drugs

Object:It is well known that drug-induced hepatotoxicity is one of the most common causes of liver damage,and severe liver damage will endanger human life.Therefore,the accurate analysis and detection of hepatotoxic drugs is of great significance.Because some hepatotoxic drugs can cause severe liver damage to the human body in a short time,and their therapeutic window is quite narrow,it is necessary to have a detection method with fast analysis speed,high sensitivity and wide application range.Electrochemical methods have been widely used in drug detection,clinical chemistry,environmental monitoring and other fields due to their advantages such as high sensitivity,fast response speed,simple operation,and low cost.This study attempts to use nanoporous materials,including nitrogen and sulfur co-doped walnut shell carbon,and NiO@ZnO porous hollow microspheres,as the electrode sensitizers to construct new types of electrochemical sensors for analysis of hepatotoxic drugs.Methods:Cyclic voltammetry（CV）,differential pulse voltammetry（DPV）,electrochemical impedance spectroscopy（EIS）and other commonly used electrochemical methods were used to characterize the electrochemical behavior of two different nanoporous materials modified sensors.Scanning electron microscope（SEM）,transmission electron microscope（TEM）,BET nitrogen adsorption instrument（BET）,fourier transform infrared spectrometer（FTIR）,x-ray energy spectrometer（EDS）,x-ray powder diffraction（XRD）were used to analyze the morphology,pore diameter distribution,functional groups and element composition of the electrode.Finally,two modified electrodes were used to determine the content of three analytes（paracetamol,p-aminophenol,isoniazid）in the actual sample by DPV,and compared with high performance liquid chromatography（HPLC）.Results:In this paper,based on the advantages of nano-porous materials,such as large specific surface area,rich pore size,good conductivity and strong catalytic ability,two novel electrochemical sensors were constructed and applied to the detection of paracetamol,paracetamol and isoniazid in actual samples.The specific work is summarized as follows:（1）Simultaneous determination of paracetamol and p-aminophenol using glassy carbon electrode modified with nitrogen-and sulfur-co-doped carbon dotsWalnut shell was processed for preparing nanoporous carbon,which further underwent element doping in order to boost its performance.A novel electrochemical sensor was then built by using the nitrogen and sulfur co-doped walnut shell carbon（N,S-WSC）.Morphology and microstructure of the materials were characterized by scanning electron microscopy and Brunauer-Emmett-Teller（de）sorption which showed that N,S-WSC has a large specific surface with abundant pores.Electrochemical properties of differently modified sensors were investigated by cyclic voltammetry and electrochemical impedance spectroscopy.They demonstrated enhanced conductivity and enlarged surface after N,S co-doping.The modified electrode exhibits good catalytic ability towards paracetamol（ACOP）and p-aminophenol（PAP）,and baseline separation of their oxidation peaks（peak potential difference is 0.24 V）allows for simultaneous detection of these two compounds.Under the optimal conditions,the calibration plot is linear in the 0.1 to 220μM ACOP concentration range,with a 26 nM detection limit.Response to PAP is linear from 1.0to 300μM,and the detection limit is 38 nM（at S/N=3）.The sensor was successfully applied to quantify ACOP and PAP in tablets,and the accuracy of results is validated by HPLC.（2）A novel electrochemical sensor based on MOF-derived NiO@ZnO hollow microspheres for isoniazid detectionAn electrochemical sensor based on metal-organic framework（MOF）-derived NiO@ZnO hollow microspheres was constructed through the coordination reaction of terephthalic acid with Zn²⁺and Ni²⁺.And its sensing performance was investigated by using isoniazid as the model analyte.Morphology characterization showed that the MOF microsphere owns circular core-shell structure with pores on its surface.Further electrochemical characterization of the prepared sensor by cyclic voltammetry（CV）and differential pulse voltammetry（DPV）proved that the material has good electrical conductivity and strong catalytic ability.Distinct oxidation peaks can be observed for INZ at potentials of 0.22 V（vs.SCE）.Under the optimal experimental conditions,the linear range of the sensor for detecting isoniazid via DPV was 0.8⁸00μM and the detection limit was 0.25μM（S/N=3）.In addition,the sensor displayed good stability,repeatability and reproducibility.The established method was successfully applied for analysis of isoniazid in tablets and mouse serum with admirable accuracy and reliability.Conclusion:In this paper,two highly sensitive electrochemical sensors for the detection of hepatotoxic drugs were successfully constructed by using nano-porous materials as electrode sensitizing materials.Modification of N,S-WSC and NiO@ZnO hollow microspheres on the surface of the bare electrode can significantly reduce the detection limit of the sensor,increase the sensitivity of the sensor,and enhance the analytical performance of the electrochemical sensor,thereby meeting the actual detection needs of hepatotoxic drugs.In addition,the two nano-porous materials have the advantages of simple preparation,low cost and abundant sources,which provide potential possibilities for the commercialization and marketization of the sensor.At the same time,the sensor analysis method is expected to play a broad role in biomedical science,energy storage and conversion,environmental protection,food safety control and other fields.