Highly sensitive quantification of vancomycin in plasma samples using liquid chromatography-tandem mass spectrometry and oral bioavailability in rats.
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 micro l of plasma with 300 micro l of 10% trifluoroacetic acid-methanol (2:1, v/v), the supernatant was diluted with 300 micro l 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 micro l. The calibration curve had a linear range from 0.01 to 20 micro g/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.
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Nakauchi-cho 5, Misasagi, Yamashina-ku, 607-8414, Kyoto, Japan. shibata@mb.kyoto-phu.ac.jp
Nobuhito
N
Shibata
Makoto
M
Ishida
Yarasani Venkata Rama
YV
Prasad
Weihua
W
Gao
Yukako
Y
Yoshikawa
Kanji
K
Takada
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001682:Biological Availability; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D014640:Vancomycin