Study of the stability of polymyxins B(1), E(1) and E(2) in aqueous solution using liquid chromatography and mass spectrometry.
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 degrees C) 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 B(1) 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.
Orwa
J A
JA
Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, Van Evenstraat 4, B-3000 Leuven, Belgium.
Govaerts
C
C
Gevers
K
K
Roets
E
E
Van Schepdael
A
A
Hoogmartens
J
J
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003091:Colistin / Q000737:chemistry*; D004355:Drug Stability; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods*; D011113:Polymyxins / Q000031:analogs & derivatives* / Q000737:chemistry*; D012996:Solutions
D000900:Anti-Bacterial Agents; D011113:Polymyxins; D012996:Solutions; C121746:polymyxin B(1); D003091:Colistin