title: Profiling analysis of low molecular weight heparins by multiple heart-cutting two dimensional chromatography with quadruple time-of-flight mass spectrometry.
abstract: Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215021, China.
authors.forename: Yilan
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Shanghai Green-Valley Pharmaceutical Co. Ltd. , Shanghai, 201200, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215021, China.
authors.forename: Yinxiu
authors.initials: Y
authors.lastname: Rong
authors.affiliation: Agilent Technology (China) Co. Ltd. , Shanghai, 201008, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Song
authors.affiliation: Shanghai Green-Valley Pharmaceutical Co. Ltd. , Shanghai, 201200, China.
authors.forename: Lv
authors.initials: L
authors.lastname: Shi
authors.affiliation: Agilent Technology (China) Co. Ltd. , Shanghai, 201008, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Agilent Technology (China) Co. Ltd. , Shanghai, 201008, China.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215021, China.
authors.forename: Naiyu
authors.initials: N
authors.lastname: Xu
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute , 110 8th Street, Troy, New York 12180, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215021, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry*; D013058:Mass Spectrometry; D013997:Time Factors
chemical_list: D006495:Heparin, Low-Molecular-Weight