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Antimicrobial Agents and Chemotherapy, April 2003, p. 1364-1370, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1364-1370.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Stability of Colistin and Colistin Methanesulfonate in Aqueous Media and Plasma as Determined by High-Performance Liquid Chromatography

Jian Li,1,{dagger} Robert W. Milne,1* Roger L. Nation,1,{dagger} John D. Turnidge,2 and Kingsley Coulthard3

Centre for Pharmaceutical Research, University of South Australia, Adelaide, South Australia 5000,1 Department of Microbiology and Infectious Diseases,2 Department of Pharmacy, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia3

Received 3 December 2001/ Returned for modification 28 April 2002/ Accepted 21 January 2003

The stabilities of colistin and colistin methanesulfonate (CMS) in different aqueous media were studied by specific high-performance liquid chromatography (HPLC) methods. Colistin was stable in water at 4 and 37°C for up to 60 days and 120 h, respectively. However, degradation was observed when colistin was stored in isotonic phosphate buffer (0.067 M, pH 7.4) and human plasma at 37°C. The stability of CMS from three different sources in water was explored by strong-anion-exchange (SAX) HPLC for CMS and by measuring the concentrations of colistin formed from the hydrolysis of CMS. The peaks of CMS in SAX HPLC disappeared almost completely after 12 h at 37°C, but appeared to remain intact for up to 2 days at 4°C. Over the same period, there was no formation of colistin at 4°C. In water, phosphate buffer, and plasma, there was rapid formation of colistin within 24 to 48 h at 37°C from the three sources of CMS. The hydrolysis products were assumed to be a complex mixture of many different sulfomethyl derivatives, including colistin. The stability of a fourth source of CMS in Mueller-Hinton broth examined during 30 min at 37°C revealed no formation of colistin. Along with previous microbiological studies, this suggested that different sulfomethyl CMSs possess intrinsic antibacterial activity. These results will be helpful for understanding the pharmacokinetics and pharmacodynamics of colistin and CMS in humans and animals.

* Corresponding author. Mailing address: Centre for Pharmaceutical Research, University of South Australia, Adelaide, South Australia 5000, Australia. Phone: 61 8 8302 2335. Fax: 61 8 8302 2389. E-mail: Robert.Milne{at}unisa.edu.au.

{dagger} Present address: Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia.

Antimicrobial Agents and Chemotherapy, April 2003, p. 1364-1370, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1364-1370.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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