Brain Penetration of Colistin in Mice Assessed by a Novel High-Performance Liquid Chromatographic Technique

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 (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. Colistin (also known as polymyxin E) is a cationic polypep-tide antibiotic and is bactericidal against multidrug-resistant gram-negative pathogens (8). Like other members of the poly-myxin family, colistin consists of two major components (colistins A and B), with colistins A and B differing only in th