Use of directly coupled ion-exchange liquid chromatography-mass spectrometry and liquid chromatography-nuclear magnetic resonance spectroscopy as a strategy for polar metabolite identification

Ion-exchange LC-MS and LC-NMR have been successfully used to identify a nov el N-acetyl metabolite of a highly polar drug candidate [2-(ethanimidoylami no)ethyl]sulfonyl alanine (GW273629) under development as a therapeutic age nt. This has been achieved using a simple HPLC method without the need for complicated and time consuming pre- or post-column derivatisation, Ion-exch ange chromatography using simple ionic strength buffer and organic solvent mobile phases, as applied here, should be suitable for the analysis of othe r charged polar species. Optimisation of the system described could result in the development of a rational generic HPLC approach specifically designe d for the characterisation of polar drug molecules and their metabolites. ( C) 2000 Elsevier Science B.V. All rights reserved.