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

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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-tetra-hydrofuran-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. 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.
Original languageEnglish
Pages (from-to)4247 - 4251
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number10
DOIs
Publication statusPublished - 2009

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