A high-pressure liquid chromatographic assay was developed for the quantitative analysis of a new cephalosporin, BMY-28142, in plasma and urine. The plasma method involved protein precipitation with acetonitrile and trichloroacetic acid followed by extraction of the acetonitrile into dichloromethane. After centrifugation, the organic phase was discarded, the aqueous solution was injected into a reverse-phase column, and peaks were detected at 280 nm. The urine method involved dilution of a urine sample with sodium acetate buffer (pH 4.25) and direct injection into the high-pressure liquid chromatography system. The assay validation data indicate that the assays for BMY-28142 in plasma and urine were specific, accurate, and reproducible. The analytical methods were applied to the determination of protein binding in human serum and to a pharmacokinetic study in rats. The results of the protein-binding study indicated that BMY-28142 was 16.3% bound to human serum proteins. In the pharmacokinetic study in rats, the maximum level in plasma of 38.7 ,ug/ml was achieved at 2.33 h after administration of a subcutaneous dose of 100 mg/kg. The levels in the plasma then declined with an elimination half-life of about 0.56 h. The mean values for the steady-state volume of distribution and total body clearance were 0.46 liters/kg and 11.9 ml/min per kg, respectively. The 0-to 24-h excretion of intact BMY-28142 in urine accounted for 88.6% of the dose.

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Cefprozil, a new oral cephalosporin, consists of a 90:10 cis:trans isomer mixture. Sensitive, specific and reproducible high performance liquid chromatographic methods have been developed for the simultaneous quantification of the two stereoisomers of cefprozil in plasma and urine samples from human and rats. Cephalexin acted as the internal standard. Plasma protein was precipitated with acetonitrile and trichloracetic acid with subsequent extraction of acetonitrile. After vortexing and centrifuging, the aqueous phase was injected onto a reverse phase C8 column. Urine samples were acidified with sodium acetate buffer (pH 3.8) and then directly injected onto a reverse phase C18 column. The detector was set at 280 nm. These methods were applied to determine protein binding of both isomers in human and rat sera, and to perform a pharmacokinetic study in human. Results showed that both isomers bound moderately to serum proteins with no interference by the other isomer. The pharmacokinetic study in human indicated that cefprozil was well absorbed and the cis and trans isomers have similar pharmacokinetics.