Simultaneous determination of novel β-lactamase inhibitor WCK 4234 and Meropenem in dog plasma by LC-MS/MS and its application to preclinical pharmacokinetic study.

Abstract

A precise and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS) bioanalytical method has been developed and validated for the simultaneous quantification of WCK 4234 and meropenem (MEM) in dog plasma. Protein precipitation using acetonitrile was employed as a sample preparation approach. Cefepime was used as an internal standard. The developed method was selective, sensitive (limit of quantification, 0.075 μg/ml for both drugs), accurate (recovery > 90%), precise (CV <10%) and linear (r2 ≥0.99, concentration range 0.075-120 μg/ml for both analytes). The developed method was successfully applied for the determination of both drugs in plasma to assess the pharmacokinetics in beagle dogs. WCK 4234 + MEM in a 1:1 ratio at 15 + 15 and 30 + 30 mg/kg doses were administered by the intravenous route. The mean plasma concentration and area under the concentration-time curve of WCK 4234 ranged from 38.3 to 77.4μg/ml and from 47.8 to 77.1μg h/ml, respectively, and the values for MEM ranged from 52.2 to 115.3μg/ml and 70.5 to 133.6μg h/ml respectively. The elimination half-life of WCK 4234 and MEM was around 0.8h.