On-line coupling of in vivo microdialysis with capillary electrophoresis/electrochemistry Original Research Article

A separation-based biosensor that couples microdialysis directly to capillary electrophoresis with electrochemical detection (CEEC) is described. The system employs a 60 nl injection valve and a gap junction interface. For successful electrochemical detection, it is necessary to apply the separation voltage at the gap interface. This is in contrast to previously reported optically based systems in which it was possible to place the high voltage at the detection end. To protect the experimental animal from the high voltage employed for the separation, a cellulose acetate-based decoupler was placed between the injection valve and the injection interface. The effects of interface gap distance, transfer buffer flow rate and capillary i.d. on separation efficiency and peak height were investigated. In particular, it was found that electrokinetic injection of positively charged analytes into the CE was affected by the magnitude of the second field set up in the transfer capillary. The use of a 25 μm diameter capillary for the transfer line and a 75 μm capillary for the CE separation gave the best detector response and highest separation efficiency. The potential of this system for bioanalytical studies was demonstrated by monitoring transdermal delivery of nicotine following administration of a nicotine patch. Cutaneous concentrations of nicotine were monitored over a 24 h period with a resolution of 10 min.