Liquid chromatographic/electrospray ionization mass spectrometric identification of the oxidation end-products of metformin in aqueous solutions

✍ Scribed by F. Collin; H. Khoury; D. Bonnefont-Rousselot; P. Thérond; A. Legrand; D. Jore; M. Gardès-Albert

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 405 KB
• Volume: 39
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.656

✦ Synopsis

Abstract

Metformin is an antihyperglycemic drug that exhibits some antioxidant properties. HO^•^‐induced oxidation of metformin was studied in aqueous solution, in both aerated and deaerated conditions. Gamma radiolysis of water was used to generate HO^•^ free radicals, capable of initiating one‐electron oxidation of metformin. Oxidation end‐products were identified by direct infusion mass spectrometry (MS) and high‐performance liquid chromatography/mass spectrometry (HPLC/MS^n^): for every product, structure elucidation was based on its mass (simple mass spectra confirmed by HPLC/MS). In addition, fragmentation spectra (MS^2^, MS^3^ and MS^4^) and the determination of deuterium–hydrogen exchange sites provided valuable information allowing the complete identification of some of the end‐products. At low radiation dose, four products were identified as primary ones, since they result from the direct attack of HO^•^ radicals on metformin. These primary oxidation end‐products were identified respectively as hydroperoxide of metformin, covalent dimer of metformin, methylbiguanide and 2‐amino‐4‐imino‐5‐methyl‐1,3,5‐triazine. At high radiation dose, seven other products were identified as secondary ones, resulting from the HO^•^‐induced oxidation of the primary end‐products. A reaction scheme was postulated for the interpretation of the results. Copyright © 2004 John Wiley & Sons, Ltd.