Analysis of heparin oligosaccharides by capillary electrophoresis-negative-ion electrospray ionization mass spectrometry

摘要

Most hyphenated analytical approaches that rely on liquid chromatography-MS require relatively long separation times, produce incomplete resolution of oligosaccharide mixtures, use eluents that are incompatible with electrospray ionization, or require oligosaccharide derivatization. Here we demonstrate the analysis of heparin oligosaccharides, including disaccharides, ultra low molecular weight heparin, and a low molecular weight heparin, using a novel electrokinetic pump-based CE-MS coupling eletrospray ion source. Reverse polarity CE separation and negative mode electrospray ionization were optimized using a volatile methanolic ammonium acetate electrolyte and sheath fluid. The on-line CE hyphenated negative-ion electrospray ionization MS on an LTQ Orbitrap mass spectrometer was useful in disaccharide compositional analysis, bottom-up and top-down analysis of low molecular weight heparin. The application of this CE-MS method to ultra low molecular heparin suggest that a charge state distribution and the low level of sulfate group loss that is achieved make this method useful on-line tandem MS analysis of heparins.