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Antimicrobial Agents and Chemotherapy, October 2009, p. 4247-4251, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00485-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Liang Jin, Jian Li, Roger L. Nation, and Joseph A. Nicolazzo*

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia

Received 13 April 2009/ Returned for modification 8 July 2009/ Accepted 31 July 2009

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.

* Corresponding author. Mailing address: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia. Phone: 61 3 9903 9605. Fax: 61 3 9903 9583. E-mail: joseph.nicolazzo{at}pharm.monash.edu.au

{triangledown} Published ahead of print on 10 August 2009.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4247-4251, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00485-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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