Fabrication Of Electrochemical And Electrochemiluminescence Sensors Based On Nanomaterials And Their Application In The Analysis Of Nitrogen Containing Drugs

Drug is patron saint of human health and life safety which plays an irreplaceable role in the process of human civilization.The establishment of analytical methods with merits of accurate and rapid is the basics of drug production and use safety and pharmacokinetics research.With their intrinsic advantages of simple apparatus,fast analysing speed and high sensitivity,electrochemical(EC)and electrochemiluminescence(ECL)methods have been widely used in the analysis of active ingredients in pharmaceutical preparations and biological fluids.The presence of lone pair electrons in nitrogen-containing drug molecules usually has certain electrochemical activity,and the electrochemical methods have been widely used in the analysis of such substances.In this dissertation,several nanomaterials such as polymer membranes,carbon nanotubes and graphene were employed to the fabrication of electrochemical and electrochemiluminescent sensors for the voltammetric and ECL analysis of several common nitrogen-containing drugs such as procaterol hydrochloride,dopamine,uric acid,bromhexine hydrochloride,tiopronin,ribavirin and methimazole.There are seven chapters in this disertation and the main contents are listed below:In Chapter 1,the research progress of EC and ECL technology in the field of drug analysis was summarized.The emphasis is on the fabrication and drug analysis application of EC and ECL sensors based on polymer membranes,carbon nanotubes and graphene.Finally,the main contents and significances of this paper were brifely described.In Chapter 2,with the help of cyclic voltammetry technology,glutamic acid monome was successfully electro-deposited onto the surface of carboxyl functionalized multiwalled carbon nanotubes(MWCNTs-COOH)/polyvinyl alcohol(PVA)modified glassy carbon electrode(GCE)to construct a poly(glutamic acid)(p-Glu)/MWCNTs-COOH/PVA composite modified GCE.The as prepared modified electrode exhibited good electrocatalytic property towards the electro-oxidation of procaterol hydrochloride(ProH)by greatly enhancing its oxidation peak current,and based on which a sensitive electrochemical method was established for the determination of ProH.Interference experiment results revealed that the fabricated sensor has strong anti-interference ability to the common coexisting substances in pharmaceutic preparation and body fluids.The method developed in present work can be applied to detect ProH in the commercial pharmaceutical preparations and human urine with satisfied results.In Chapter 3,with ProH as monomer,poly(procaterol hydrochloride)(p-ProH)membrane modified GCE was successfully prepared by simple cyclic voltammogram scanning technology.Based on the detailed study of the electrochemical behavior of p-ProH membrane on the GCE,the possible formation mechanism of p-ProH membrane on the GCE surface was proposed.Based on the catalytic effect of the modified electrode on the electrochemical oxidation of dopamine and uric acid,the simultaneous electrochemical determination of dopamine and uric acid was achieved using square wave voltammetry technology.Finally,the applicability of p-ProH/GCE for sensing dopamine and uric acid in biological samples was validated employing human serum and urine as real samples,recoveries ranging from 87.3 to 113.4%were obtained.In Chapter 4,on the basis of the successful preparation of p-ProH/GCE in the previous chapter,MWCNTs-COOH was further introduced to prepare a p-ProH/MWCNTs-COOH composite modified GCE.Due to the introduction of MWCNTs-COOH,the electrochemical response of bromhexine hydrochloride(BrH)on the composite modified GCE was much greater than that of p-ProH/GCE and MWCNTs-COOH/GCE.Based on this,a highly sensitive voltammetric method for the determination of BrH was established.The as prepared composite film modified electrode showed excellent stability and anti-interference ability in the determination of BrH in pharmaceutical preparations and simulated human serum.In Chapter 5 and 6,the classic reagent of tris(2,2'-bipyridine)ruthenium(II)(Ru(bpy)32+)was used as the ECL luminophor.Based on the ECL enhancing effect of tiopronin,quenching effect of ribavirin to the ECL of Ru(bpy)32+ system,ECL methods for the determination of tiopronin and ribavirin were established.The coreaction of these two substances in Ru(bpy)32+ ECL system were also proposed.In Chapter 7,a new type of an Ag3Cu5 heterometal lic alkynyl cluster([Ag3Cu5(C=CC6H4CH3-4)6(?-dpppy)3](ClO4)2(dpppy = 2,6-bis(diphenylphosphino)-pyridine))was selected as the ECL reagents,to fabricated a solid-stated ECL sensor with the help of grapheme.Based on the quenching effect of the nitrogen-containing heterocyclic drug-methimazole(MMZ)on the ECL of the newly prepared solid-state ECL electrode,a new method for the determination of MMZ was developed.Under the optimal conditions,the quenching value of ECL intensity was linear with the logarithmic value of MMZ concentration in the range of 2.0 x 10-8 to 1.0 × 10-4 M(R= 0.9919).The detection limit(S/N-3)was 5.0 × 10-9 M,and the relative standard deviation of 15 consecutive ECL peak values was 1.8%for 1.0 ×10-6 M methimazole measurements.The method was successfully applied to the determination of methimazole in pharmaceutical samples and satisfactory results were obtained.