CAPILLARY-ELECTROPHORESIS WITH LASER-INDUCED FLUORESCENCE - A ROUTINEMETHOD TO DETERMINE MOXIFLOXACIN IN HUMAN-BODY FLUIDS IN VERY SMALL SAMPLE VOLUMES

The feasibility of capillary electrophoresis with HeCd laser-induced f luorescence detection as a validated routine method for bioanalytical analysis is reported. Method evaluation, validation and results of the determination of moxifloxacin (BAY 12-8039), a new antimicrobially ac tive g-methoxy-quinolone, in plasma and microdialysate are described. After a one step sample preparation the samples can be injected direct ly into the capillary. The volume of microdialysate and plasma, respec tively, needed for more than 50 injections is only 10 mu l and 20 mu l . Total run time is less than 7 min using a 27 cm capillary on commerc ial instrumentation. An analysis time of less than 1 min was shown to be possible, however it could not be used routinely since appropriate instrumentation was not available. Evaluation is based on the relative corrected peak area (analyte/I.S.). The method's dynamic range compri ses three orders of magnitude (plasma: 2.5-5000 mu g/l; microdialysate : 5-5000 mu g/l). Validation according to international guidelines yie lded data on accuracy and precision of the method throughout the entir e working range of;inter-day precision: plasma <6%, microdialysate <5% and inter-day accuracy: plasma <2%, microdialysate <4%. The crossvali dation with an existing HPLC method utilizing clinical study samples s hows Linear correlation. In view of its adequate sensitivity and high selectivity capillary electrophoresis with laser-induced fluorescence is a very versatile tool in pharmacokinetic studies of quinolones, esp ecially in situations with limited sample volumes: e. g. pediatrics, p atients at risk, animal-, microdialysis- and tissue-kinetic studies. V alidation parameters and other features, like high sample throughput a nd robustness, are comparable to or even better than HPLC. Further nec essary improvements of the capillary electrophoresis with laser-induce d fluorescence instrumentation (autosampler, vials, parallel capillari es) and its use in bioanalytical routine analysis are discussed. (C) 1 998 Elsevier Science B.V. All rights reserved.