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.

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.

• Authors: Jie He, Song Gao, Ming Hu, Diana S-L Chow, Vincent H Tam
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 68 Issue 5 Pg. 1104-10 (May 2013) ISSN: 1460-2091 [Electronic] England
• PMID: 23341128 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Validation Study)

Chemical References

• Anti-Bacterial Agents
• Polymyxin B

Topics

• Animals
• Anti-Bacterial Agents (analysis, pharmacokinetics)
• Body Fluids (chemistry)
• Chromatography, Liquid (methods)
• Female
• Mice
• Polymyxin B (analysis, pharmacokinetics)
• Reproducibility of Results
• Tandem Mass Spectrometry (methods)