The development of some electrochemical detection systems using microelectrodes and their application to biomedical analysis

The main objectives of this doctoral thesis were to develop sensitive and versatile electrochemical detection systems, taking advantage of the unique analytical characteristics of microelectrodes, and apply them to selected biomedical analyses. In order to broaden the applicability of electrochemical detection following capillary electrophoresis (CE), a system was developed which enabled reductive electrochemical detection to be earned out following capillary electrophoresis. This greatly broadens the number of compounds that can be detected electrochemically following separation by CE The analytical potential of the system was demonstrated for both mtroaromatic compounds and quinones It was shown to possess major advantages over reductive LCEC, including very short deoxygenation times and low limits of detection. The system was also applied to the analysis of an antitumour compound, mitomycin C, in human serum without the need for prior extraction procedures.\ud \ud In another project, continuous in vivo microdialysis sampling was used in conjunction with capillary electrophoresis and electrochemical detection, to monitor the levels of tryptophan and its metabolites in the extracellular fluid of rat brain. The relative changes in the concentration of these metabolites in the extracellular fluid were monitored following mtrapentoneal administration of tryptophan and kynuremne, respectively. The advantages of capillary electrophoresis for sample volume limited analyses were demonstrated, and the high sensitivity of electrochemical detection was shown to be very desirable in this field of research.\ud \ud In the area of biomedical analysis one of the major objectives is to develop very sensitive techniques for the determination of therapeutic compounds in biological fluids. The advantages of microelectrodes and adsorptive stripping voltammetry were combined by developing a mercury thin film ultramicroelectrode using a carbon fibre substrate. Using phase-selective AC stripping voltammetry, a very sensitive technique was developed for the analysis of methotrexate, aminoptenn, and edatrexate, members of the very important ptendine class of chemotherapeutic drugs. These compounds were analysed in human unne and serum, both with and without the employment of prior extraction procedures.\ud \ud Carbon fibre electrodes were also modified with the polymer\ud [Os(bipy)2(PVP)2()Cl]Cl for the flow amperometnc determination of nitrite. This redox polymer greatly enhances the kinetics of nitrite reduction compared with the reaction at bare carbon electrodes Due to the electrocatalytic effect, a less extreme working potential could be employed which minimised the responses from the commonly present interferents present in real samples. The electrode was applied to the flow amperometnc determination of nitnte in processed meat samples. The electrode exhibited excellent selectivity and long term stability