The overall objective of this study is to develop a system that can be used to monitor pharmacokinetic, pharmacological or neurochemical events in near real time. This will be accomplished by coupling microdialysis sampling directly to capillary electrophoresis (CE). The system is much more versatile than conventional biosensors since the sampling and analysis steps can be optimized separately. A system has been developed using CE with LIF detection at 442 nm. In this proposal, an on-line derivatization system will be constructed in order to expand the applicability of the current system for the analysis of primary amines. The development of a shunt probe for portal vein sampling will also be investigated. Lastly, software will be written for near real-time plotting of the data. These three components will form the basis of an instrument which is capable of monitoring and plotting blood levels of a drug in near real time with a temporal resolution of less than one minute. In Phase II, the system will be expanded to include an electrochemical detector. Probes for tissue sampling will also be evaluated. This instrument should find wide applicability in the pharmaceutical and biomedical industries.
The system proposed will find commercial application as a drug development tool in the pharmaceutical industry and also for fundamental biomedical research in universities and government laboratories. BAS currently addresses these markets world-wide, and the new system would be compatible with existing BAS products.
| Freed, A L; Cooper, J D; Davies, M I et al. (2001) Investigation of the metabolism of substance P in rat striatum by microdialysis sampling and capillary electrophoresis with laser-induced fluorescence detection. J Neurosci Methods 109:23-9 |
