Liquid chromatography-mass spectrometry study towards the pH and temperature-induced N-acyl migration in polymyxin B
article
In the course of the synthesis and purification of new polymyxins and analogues, formation of a by-product with identical mass was observed and it was believed that this might be the result of acyl migration from the Nα- to the Nγ-position of residue α,γ-diaminobutyric acid 1 (Dab1) under acidic conditions. Therefore, a LC-MS/MS study was initiated to establish the stability of polymyxin B3 in aqueous solution at room temperature and 60°C, as well as different pH values (i.e. 1.4, 4.4 and 7.4). It was shown that the by-product, which is actually formed in the course of the purification of polymyxin B3 after evaporation in acidic medium, has a retention time similar to Nγ-polymyxin B3. Acyl-migration occurred most rapidly at 60°C and pH 7.4. Furthermore, it was established that migration of the acyl from the Nα- to the Nγ-position of residue Dab1 is reversible and that the equilibrium seems to be in favor of the Nα-acylated compound. © 2004 Elsevier B.V. All rights reserved.
Topics
Acyl migrationpHStability studyTemperatureAcylationEvaporationMass spectrometryOrganic acidspH effectsPurificationSolutionsSynthesis (chemical)Acyl migrationPolymyxinsLiquid chromatographyDiaminobutyric acidPolymyxin BPolymyxin derivativeAcidityAnalytic methodDrug purificationDrug stabilitypH measurementTandem mass spectrometryTemperatureTemperature dependenceAmino acid sequenceAnti-bacterial agentsHydrogen-ion concentrationMass spectrometryPolymyxin BDiaminobutyric acid, 27252-32-0Polymyxin B, 1404-26-8, 1405-20-5Anti-bacterial agents
TNO Identifier
238097
ISSN
00219673
Source
Journal of Chromatography A, 1058(1-2), pp. 183-189.
Pages
183-189
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