Highly sensitive quantification of vancomycin in plasma samples using liquid chromatography–tandem mass spectrometry and oral bioavailability in rats

Abstract

We developed a highly sensitive liquid chromatography–tandem mass spectrometry assay (LC–MS–MS) for a glycopeptide antibacterial drug, vancomycin (VCM), in rat plasma. After precipitating 100 μl of plasma with 300 μl of 10% trifluoroacetic acid–methanol (2:1, v/v), the supernatant was diluted with 300 μl of distilled water and was passed through a filter. LC–MS–MS equipped with electrospray ionization in the positive ion mode used a pair of ions at 725/144 m/ z for VCM in the multiple reaction-monitoring mode with a sample injection volume of 20 μl. The calibration curve had a linear range from 0.01 to 20 μg/ml when linear least square regression was applied to the concentration versus peak area plot. The drug in the sample was detected within 5 min. Precision, accuracy and limit of quantitation indicated that this method was suitable for the quantitative determination of VCM in rat plasma. Using this method, we defined for the first time that the oral bioavailability of VCM in rats was 0.069%. This method can be applied to basic pharmacokinetic and pharmaceutical studies in rats.