Microdialysis sampling has become an important means of continuously m
onitoring reactions in vivo. This sampling technique places a constrai
nt on the analysis method because of the very small sample volume prov
ided. On the other hand, microdialysis provides the advantage of clean
samples that do not require cleanup prior to analysis. An on-line cou
pling of microdialysis sampling to capillary electrophoretic; (CE) ana
lysis is described that uses the advantages of microcolumn separations
to overcome the small volume limitation. An interface was designed wh
ich converts the continuous microdialysis sample stream into discrete
60-nL sample plugs and then injects a portion of this plug into the CE
system. The on-line interface provided precision of 2.6% with minimal
band broadening or peak height loss relative to off-line sampling. Us
ing a high-speed micellar electrokinetic chromatography (MEKC) separat
ion, resolution of the investigational antineoplastic SR 4233 from its
main metabolite SR 4317 was achieved in less than 60 s. This allowed
the on-line system to achieve a 90-s temporal resolution for determini
ng the pharmacokinetics of SR 4233 in vivo.