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

A method based on microdialysis sampling combined with high-performance liquid chromatography (HPLC) has been developed for monitoring the anti-HIV agent PD-161374 (isothiazolone) and its thiol and disulfide metabolites in blood. It was demonstrated that unlike blood withdraw and extraction, microdialysis sampling can preserve the distribution among the isothiazolone and its metabolites in blood. The use of a narrow-bore HPLC system, combined with the relatively high probe extraction efficiency (approximately 50%) from the flexible probe design in this work, allows the direct and quantitative determination of the drug and its major metabolites at submicromolar level.