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- Title
A validated ultra-performance liquid chromatography–tandem mass spectrometry method for the quantification of polymyxin B in mouse serum and epithelial lining fluid: application to pharmacokinetic studies.
- Authors
He, Jie; Gao, Song; Hu, Ming; Chow, Diana S.-L.; Tam, Vincent H.
- Abstract
Objectives A rapid, sensitive and robust ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantification of four major polymyxin B components (polymyxin B1, polymyxin B2, polymyxin B3 and isoleucine-polymyxin B1) in serum and epithelial lining fluid (ELF) samples. Methods A Waters Acquity UPLC HSS C18 column was used with 0.1% formic acid in water/acetonitrile as mobile phases. Analysis was performed in a positive ionization mode with multiple-reactions monitoring scan type. Five percent trichloroacetic acid was used to precipitate proteins in biological samples and to increase the sensitivity of detection. Results Our results showed a linear concentration range of 0.0065–3.2 mg/L for all the major polymyxin B components in both serum and ELF, respectively; the interday variation was <10% and the accuracy was 88%–115%. The validated method was used to characterize the pharmacokinetics (serum and ELF) of polymyxin B in mice. Conclusions This is the first report, to date, examining the individual pharmacokinetics of various polymyxin B components in mice. Our results revealed no considerable differences in clearances among the components. The limited exposure of polymyxin B in ELF observed was consistent with the less favourable efficacy of polymyxin B reported for the treatment of pulmonary infections. This method can be used to further examine the pharmacokinetics of polymyxin B in a variety of clinical and experimental settings.
- Subjects
LIQUID chromatography; CHROMATOGRAPHIC analysis; TANDEM mass spectrometry; MASS spectrometry; POLYMYXIN B
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2013, Vol 68, Issue 5, p1104
- ISSN
0305-7453
- Publication type
Article