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. 2013 May;68(5):1104-10.
doi: 10.1093/jac/dks536. Epub 2013 Jan 22.

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

Jie He  1 , Song Gao, Ming Hu, Diana S-L Chow, Vincent H Tam
Affiliations

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

Jie He et al. J Antimicrob Chemother. 2013 May.

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.

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Figures

Figure 1.
Figure 1.
Chemical structures of PB1, PB2, PB3 and Ile-PB1.
Figure 2.
Figure 2.
MS2 full scans for PB1 (a), PB2 (b), PB3 (c) and Ile-PB1 (d).
Figure 3.
Figure 3.
Chromatograms of PB1, PB2, PB3, Ile-PB1 and carbutamide [internal standard (IS)] in a mouse serum sample.
Figure 4.
Figure 4.
Serum and ELF concentrations of PB1, PB2, PB3 and Ile-PB1 after an intravenous administration of 3 mg/kg polymyxin B (USP) (n = 4). Drug concentrations in ELF could only be detected for up to 4 h post-dose.
See this image and copyright information in PMC

References

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