| This dissertation describes the development of methods for the analysis of drugs in body fluids using microdialysis sampling and capillary electrophoresis.;A micellar capillary electrophoresis (MCCE) separation of caffeine, theobromine, paraxanthine, 1,3,7-trimethyluric acid and theophylline was developed using sodium dodecyl sulphate (SDS) as a micellar phase. The effects of pH, micelle concentration, buffer concentration, ionic strength, buffer type, applied voltage and injection time were studied. The optimum conditions for the determination of caffeine and its four analogues in pharmaceutical tablets, beverages and physiological fluids were indicated. Caffeine and its four analogues could be well separated within 100 seconds with detection limits of less than 1;A unique pH-mediated on-column sample concentration method was developed. This method utilized an electrokinetic injection process to introduce negatively charged analytes into a running buffer, and then a local pH titration of the buffer to obtain a low conductivity zone and a high degree of electrofocusing of charged analytes. With the use of this pH-mediated method and a CE-UV system, great sensitivity enhancement for physiological samples was achieved without loss in resolution. Compared to a normal CE-UV method, the sensitivity was increased by more than 66-fold. A detection limit of 0.3;A high efficiency LC-CE on-line sample concentration method with sample matrix switching and stacking procedures was developed. Compared to a normal CE-UV method with a hydrodynamic injection, the sensitivity was increased by more than 500-fold without loss in resolution. A limit of detection of less than 10nM for primaquine, bupivcaine and doxepin in a microdialysis sample was achieved. This method can be used for anionic or cationic analytes. This method is also a good two-dimensional analytical technique for analytes which can not be resolved by a liquid chromatography or CE alone. Compared to other analytical method for biological samples, this method coupled with microdialysis sampling is fast, easy and simple to use without requiring any sample pretreatment procedure for a physiological sample.;One approach to calibrating a microdialysis probe in vivo is to determine the amount of a test compound that diffuses out of the membrane relative to the amount in the perfusate (extraction efficiency by delivery,... |
