Microdialysis sampling of the isothiazolone, PD-161374, and its thiol and disulfide metabolites

A method based on microdialysis sampling combined with high-performance liq uid chromatography (HPLC) has been developed for monitoring the anti-HIV ag ent PD-161374 (isothiazolone) and its thiol and disulfide metabolites in bl ood. It was demonstrated that unlike blood withdraw and extraction, microdi alysis sampling can preserve the distribution among the isothiazolone and i ts metabolites in blood. The use of a narrow-bore HPLC system, combined wit h the relatively high probe extraction efficiency (similar to 50%) from the flexible probe design in this work, allows the direct and quantitative det ermination of the drug and its major metabolites at submicromolar level. (C ) 2000 Published by Elsevier Science B.V.