title: Capillary Electrophoresis-Mass Spectrometry for the Analysis of Heparin Oligosaccharides and Low Molecular Weight Heparin.
abstract: Heparins, highly sulfated, linear polysaccharides also known as glycosaminoglycans, are among the most challenging biopolymers to analyze. Hyphenated techniques in conjunction with mass spectrometry (MS) offer rapid analysis of complex glycosaminoglycan mixtures, providing detailed structural and quantitative data. Previous analytical approaches have often relied on liquid chromatography (LC)-MS, and some have limitations including long separation times, low resolution of oligosaccharide mixtures, incompatibility of eluents, and often require oligosaccharide derivatization. This study examines the analysis of glycosaminoglycan oligosaccharides using a novel electrokinetic pump-based capillary electrophoresis (CE)-MS interface. CE separation and electrospray were optimized using a volatile ammonium bicarbonate electrolyte and a methanol-formic acid sheath fluid. The online analyses of highly sulfated heparin oligosaccharides, ranging from disaccharides to low molecular weight heparins, were performed within a 10 min time frame, offering an opportunity for higher-throughput analysis. Disaccharide compositional analysis as well as top-down analysis of low molecular weight heparin was demonstrated. Using normal polarity CE separation and positive-ion electrospray ionization MS, excellent run-to-run reproducibility (relative standard deviation of 3.6-5.1% for peak area and 0.2-0.4% for peak migration time) and sensitivity (limit of quantification of 2.0-5.9 ng/mL and limit of detection of 0.6-1.8 ng/mL) could be achieved.
authors.affiliation: National Glycoengineering Research Center, Shandong University , Jinan 250100, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Lin
authors.affiliation: National Glycoengineering Research Center, Shandong University , Jinan 250100, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: National Glycoengineering Research Center, Shandong University , Jinan 250100, China.
authors.forename: Lianli
authors.initials: L
authors.lastname: Chi
authors.affiliation: CMP Scientific, Corporation, 760 Parkside Avenue, Brooklyn, New York 11226, United States.|Beijing Proteomics Front Company, Limited, R&D Building, 29 Shengmingyuan Road, Changping District, Beijing 102206, China.
authors.forename: Qiangwei
authors.initials: Q
authors.lastname: Xia
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D019075:Electrophoresis, Capillary; D006493:Heparin / Q000032:analysis* / Q000737:chemistry; D006495:Heparin, Low-Molecular-Weight / Q000032:analysis* / Q000737:chemistry; D013058:Mass Spectrometry; D008970:Molecular Weight; D009844:Oligosaccharides / Q000032:analysis* / Q000737:chemistry
chemical_list: D006495:Heparin, Low-Molecular-Weight; D009844:Oligosaccharides; D006493:Heparin