DETERMINATION OF A CEPHALOSPORIN ANTIBIOTIC, CEFTIBUTEN, IN HUMAN PLASMA WITH COLUMN-SWITCHING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ULTRAVIOLET DETECTION

A column-switching high-performance liquid chromatographic assay combined with a heart-cutting technique and UV detection (LC/LC/UV) was developed to determine ceftibuten, a new oral cephalosporin, in human plasma. Plasma samples were directly injected into the first chromatographic column for samples cleanup and extraction. Thereafter, a switching valve, located at the junction of the first cleanup column and the second analytical column, opened during a 4-6-min interval after injection to transfer the segment containing ceftibuten into the analytical column for quantitation. The method was used routinely in pharmacokinetic studies and has the advantages of simplicity, improved sensitivity, and selectivity. Concentrations of ceftibuten in plasma over a range of 0.1-20-mu-g/mL can be determined with high precision and reproducibility. A single, oral, 200-mg dose of ceftibuten in humans resulted in a maximum concentration of 9.79-mu-g/mL, an area under the plot of concentration of drug in plasma versus time (0-12 h) of 47.77-mu-g.h/mL, and a half-life of 3.2 h. These results document the utility of the LC/LC/UV method in clinical pharmacokinetic studies.