Development Of Azithromycin-molecularly Imprinted Electrochemical/Electrochemiluinescent Sensor And Its Application

Azithromycin（AZM）is representative antibiotic in the third generation of macrolide antibiotics,with broad-spectrum antibacterial activity.It is applied to the skin and soft tissue infections caused by sensitive bacteria,respiratory tract infections,non-multi-resistant Neisseria gonorrhoeae and Chlamydia trachomatis of simple genital infection in clinical.However,the use of drugs is a double-edged sword.AZM brings healing,at the same time,when it accumulates over a certain value in the human bodies,it will bring some side effects.Therefore,it is important to realize the rapid,sensitive and accurate determination of AZM content in drugs and biological samples.In this study,a molecularly imprinted polymer with specific recognition ability and high adsorption capacity for AZM was prepared.The electrochemical and electrochemiluminescence sensors were constructed with specific recognition unit,which established a rapid,sensitive and highly selective electrochemical and electrochemiluminescence analysis method of AZM,the study is divided into two parts:PartⅠDevelopment of molecularly imprinted electrochemical sensor for rapid determination of trace azithromycin in pharmaceuticals and biological samplesObjective:A new electrochemical sensor based on molecularly imprinted polymers/acetylene black（MIP/AB）was developed for selective and sensitive determination of azithromycin（AZM）in pharmaceuticals and biological samples.Methods:The MIP was synthesized by precipitation polymerization.We chose MIP and AB as recognition and catalytic element respectively to modify carbon paste electrode.DPV（Differential pulse voltammetry）and CV（Cyclic voltammetry）were used to analyze the electrochemical characteristics of AZM.The parameters（electrode composition,extraction conditions and detection conditions）that affect the sensor response signal was systematically optimized,and evaluated the electrochemical analysis method.Then,the proposed sensor was used to detect AZM in pharmaceuticals and biological samples.Results:The electrochemical response signal of AZM on MIP/ABP（MIP/AB modified carbon paste）was higher than that on NIP/ABP（NIP/AB modified carbon paste）.The proposed sensor produced high capacity of resisting disturbance to macrolides structural analogues and other electrochemically active compounds,which suggested the sensor had superior selectivity for AZM.Under the optimized conditions,the prepared sensor showed a linear ranges of 1.0×10^-7 mol L^-1 to 2.0×10^-5 mol L^-1,with a limit of detection（LOD）of 1.1×10^-8 mol L^-1.The spiked recoveries of AZM in pharmaceuticals,urine and blood samples were found to be from 90.4%to 108.3%,and RSD（Relative standard deviation）changed from 0.12%to 5.1%,which were consistent with the results of HPLC-MS/MS（High-performance liquid chromatography-tandem mass spectrometry）method.Conclusions:The developed MIP/ABP based electrochemical sensor showed high sensitivity and selectivity for determination of AZM,and the results were stable and reliable.Therefore,the sensor was useful for determination of AZM in pharmaceuticals and biological samples.PartⅡDevelopment of molecularly imprinted electrochemiluminescent sensor for rapid and sensitive determination of trace azithromycin in biological samplesObjective:A molecular imprinted electrochemiluminescence sensor was established and used for rapid and sensitive detection of AZM in biological samples.Methods:The sensitive electrochemiluminescenT（ECL）sensor was developed with MIP modified carbon paste electrode,and Ru（bpy）₃²⁺was chosen as luminescence reagent.The parameters（electrode composition,extraction conditions and detection conditions）that affect the sensor response signal was systematically optimized.Then,the proposed ECL sensor was used to detect trace AZM in biological samples.Results:AZM has a significant enhancement for ECL intensity of Ru（bpy）₃²⁺.The proposed ECL sensor had superior selectivity and high sensitivity for AZM.The prepared ECL sensor showed a linear range of 1.0×10^-10 mol L^-1 to 4.0×10^-7 mol L^-1,with a limit of detection（LOD）of 2.3×10^-11 mol L^-1.The spiked recoveries of AZM in urine and blood samples were 92.0%-112.0%,and RSD was 4.9%-8.9%.Conclusions:The developed ECL sensor based on MIP show high selectivity and sensitivity to AZM.So,the proposed sensor has a great application potential in rapid and sensitive detection of trace AZM in complex biological samples.