Pharmacokinetic profile of cefbuperazone in healthy Chinese volunteers after single and multiple drip intravenous infusion by HPLC-MS/MS

A selective and reproducible HPLC-MS/MS method was developed and fully validated for the determination of cefbuperazone in human plasma and urine. Samples were prepared using protein precipitation and separated on a Zorbax Eclipse Plus C18 column (2.1×50mm, 3.5μm). The API-4000 mass spectrometer was operated under multiple reaction monitoring mode (MRM) using the electrospray ionization technique. Linearity was achieved from 0.250 to 250μg/mL in plasma and 20.0-5000μg/mL in urine. The method was successfully applied to a pharmacokinetic study of cefbuperazone in healthy Chinese volunteers after drip intravenous infusion of 0.5, 1.0, 2.0g cefbuperazone sodium injection. Cefbuperazone reached a maximum concentration (Cmax) of 44.7±8.1μg/mL, 86.7±12.7μg/mL and 168±14μg/mL in 0.5, 1.0 and 2.0g dose groups respectively, at 60min after the start of infusion. The half-life (t1/2) was between 1.8-1.9h, and the elimination constant (kel) was between 0.36-0.39h(-1). The results proved that cefbuperazone showed linear pharmacokinetic profile in the dose range of 0.5-2.0g without gender difference. Drug accumulation was not observed. Cefbuperazone reached the maximum excretion rate in urine 2h after the start of infusion. About 60.0% of the administered drug was excreted via urine as unchanged form within 12h. The cumulative excretion of cefbuperazone after single drip intravenous infusion was proportional to the administered dose within the range from 0.5g to 2.0g.

Cefbuperazone; Excretion; HPLC–MS/MS; Pharmacokinetic.