Determination of zabofloxacin in rat plasma by liquid chromatography with mass spectrometry and its application to pharmacokinetic study

The objective of the present study was to develop a rapid and sensitive method for the determination of zabofloxacin, a novel, broad-spectrum fluoroquinolone antibiotic, in rat plasma. Rat plasma samples were deproteinized with methanol, and then were injected into an LC-MS system for quantification. Zabofloxacin and enrofloxacin, which served as an internal standard, were analyzed by selected ion monitoring (SIM) at m/z transitions of 402 for zabofloxacin and 360 for the internal standard. The lower limit of quantification (LLOQ) was determined to be 10 ng/mL, with acceptable linearity ranging from 10 to 5000 ng/mL (R > 0.999). The validation parameters for zabofloxacin, such as absolute matrix effect (107.7-116.0%), accuracy (92.5-101.1% for intra-day and 90.3-103.8% for inter-day), precision (7.7-10.2% for intra-day and 4.2-8.9% for inter-day), and stability in rat plasma (96.0-101.8%), were found to be acceptable according to the assay validation guidelines of the FDA (2001). Following oral administration of zabofloxacin to rats at a dose of 20 mg/kg, the concentration of zabofloxacin in plasma was quantifiable in plasma samples collected up to 8 h following zabofloxacin administration. The method described in the present study is applicable to routine pharmacokinetic studies in rats.