AUTOMATED ANALYTICAL SYSTEMS FOR DRUG DEVELOPMENT STUDIES .4. A MICRODIALYSIS SYSTEM TO STUDY THE PARTITIONING OF LOMEFLOXACIN ACROSS AN ERYTHROCYTE-MEMBRANE IN-VITRO

An automated system utilizing microdialysis sampling, intermittent dos ing, and liquid chromatographic analysis was assembled in order to stu dy the partitioning of lomefloxacin, a fluoroquinolone antimicrobial, into human erythrocytes in vitro. The apparent erythrocyte:buffer part ition coefficient was found to be approximately 2.0 with this system a nd by a manual method. The value was concentration-dependent; lower pa rtition coefficients were observed at lomefloxacin concentrations less than 1 mu g ml(-1). At all concentrations, values obtained by microdi alysis were statistically indistinguishable from those obtained by a c onventional manual method. The results indicate that erythrocyte parti tion coefficients can be measured successfully with the microdialysis system. Furthermore, microdialysis sampling eliminates the tedious met hodology associated with traditional erythrocyte partitioning studies, including sample clean-up. Due to automated intermittent dosing and o n-line LC analysis, the system operates unattended.