High-performance liquid chromatographic methods for the determination of cefpimizole in plasma and urine.

Quantitative analytical methods have been defined for the determination of cefpimizole, a new broad-spectrum cephalosporin antibiotic, in plasma and urine specimens. The methods employ ion-pair reversed-phase high-performance liquid chromatography with both ethylene-diaminetetraacetic acid (EDTA) and tetrabutylammonium hydroxide as pairing agents for separation and ultraviolet detection at 254 nm. Sample preparation for plasma aliquots consisted of acetonitrile protein precipitation followed by phase separation; the aqueous phase was filtered and assayed. For urine, sample preparation consisted of diluting an aliquot with chromatographic eluent, filtering, and assaying. The methods had a linear range of 17-0.3 micrograms/ml for plasma and 800-15 micrograms/ml for urine and had sufficient precision and accuracy to provide quantitative data. Stability studies in plasma and urine indicated that cefpimizole degraded rapidly at room temperature. Addition of EDTA to the physiological fluid substantially increased the stability at room temperature, and little or no degradation was observed in plasma or urine stored at -30 degrees C for over 100 days. Utility of the methods was demonstrated by assaying plasma and urine specimens obtained from a human volunteer receiving three dose levels. Estimates of various pharmacokinetic parameters are presented.