High-pressure liquid chromatographic analysis of BMY-28142 in plasma and urine

Abstract

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.

Pharmacokinetics-Pharmacodynamics of Cefepime and Piperacillin- Tazobactam against Escherichia coli and Klebsiella pneumoniae Strains Producing Extended-Spectrum β-Lactamases: Report from the ARREST Program

“…The fraction of unbound drug for piperacillin-tazobactam and cefepime assumed in these analyses was 70 and 84%, respectively (2,20).…”

Effects of age and gender on pharmacokinetics of cefepime

“…Plasma and urine samples were analyzed for cefepime by a validated highpressure liquid chromatographic assay with UV detection (4). Quality control samples of plasma and urine, containing known concentrations of cefepime, were prepared before initiation of drug administration and were stored together with the study samples.…”

Bioequivalence study of cefepime intramuscular injection

“…Cefadroxil (10 μg/mL) was used as the internal standard and the samples were extracted by the method of Barbhaiya [4]. A portion of the extracted sample (75 μL) was injected using an automated injection system (Waters 717 plus Autosampler, Waters Associates, Milford, MA, USA), onto a Nova-Pak C18 column (Waters Associates).…”

“…All subjects had good tolerance and no serious adverse events were observed. Conclusion: Cefamax 1 g intramuscular formulation is bioequivalent to Maxipime 1 g intramuscular formulation based on 90% CIs for C max, AUC [0][1][2][3][4][5][6][7][8][9][10][11][12] , and AUC 0-∞ within 80%-125%. …”