Study of the stability of polymyxins B1, E1 and E2 in aqueous solution using liquid chromatography and mass spectrometry

被引:59
作者
Orwa, JA [1 ]
Govaerts, C [1 ]
Gevers, K [1 ]
Roets, E [1 ]
Van Schepdael, A [1 ]
Hoogmartens, J [1 ]
机构
[1] Katholieke Univ Leuven, Fac Farmaceut Wetenschappen, Lab Farmaceut Chem & Anal Geneesmiddelen, B-3000 Leuven, Belgium
关键词
polymyxin; stability; liquid chromatography; degradation products; mass spectrometry;
D O I
10.1016/S0731-7085(02)00016-X
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Polymyxins B-1, E-1 (colistin A) and E-2 (colistin B) were subjected to degradation in aqueous solutions of different pH values (1.4, 3.4, 5.4 and 7.4) and at different temperatures (37, 50 and 60 degreesC) in order to investigate the characteristics of decomposition. The progress of decomposition was followed by reversed-phase liquid chromatography on YMC-Pack Pro, C-18 stationary phase. The degradation curves showed (pseudo) first order kinetics. The pH-rate profiles indicate that colistin is more susceptible to degradation in solutions of pH above 5 and is more stable in acidic media. The degradation of polymyxin 13, was most rapid at pH 7.4. Qualitative analysis of the degradation products by LC/MS reveals that racemization is the major mechanism of degradation in both acidic and neutral media. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:203 / 212
页数:10
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