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Stability of colistin and colistin methanesulfonate in aqueous media and plasma as determined by high-performance liquid chromatography

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ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 47, 期 4, 页码 1364-1370

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AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.47.4.1364-1370.2003

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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 37degreesC 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 37degreesC. 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 37degreesC, but appeared to remain intact for up to 2 days at 4degreesC. Over the same period, there was no formation of colistin at 4degreesC. In water, phosphate buffer, and plasma, there was rapid formation of colistin within 24 to 48 h at 37degreesC 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 37degreesC 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.

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