Brain penetration of colistin in mice assessed by a novel high-performance liquid chromatographic technique

Antimicrob Agents Chemother. 2009 Oct;53(10):4247-51. doi: 10.1128/AAC.00485-09. Epub 2009 Aug 10.

Abstract

A sensitive and reliable liquid chromatographic method was developed and validated for the determination of colistin concentrations in mouse brain homogenate. With a mobile phase consisting of acetonitrile-tetrahydrofuran-water (50:25:25 [vol/vol]) at a flow rate of 1 ml/min, a linear correlation between peak area and colistin concentration was observed over the concentration range of 93.8 to 3,000 ng/g in brain tissue (R2 > 0.994). Intra- and interday coefficients of variation were 5.1 to 8.3% and 5.8 to 8.5%, respectively, and the recovery ranged from 85% to 94%. This assay was then utilized to determine the amount of colistin that permeated the blood-brain barrier over a 2-h period following bolus intravenous administration of colistin sulfate to mice. After a single dose of 5 mg/kg of body weight to mice, brain homogenate concentrations of colistin were very low, relative to plasma colistin concentrations, suggesting that colistin permeability across the healthy blood-brain barrier is negligible during this experimental period.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacokinetics*
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid / methods*
  • Colistin / pharmacokinetics*
  • Male
  • Mice

Substances

  • Anti-Bacterial Agents
  • Colistin