title: Liquid chromatography-diode array detection-mass spectrometry for compositional analysis of low molecular weight heparins.
abstract: Low molecular weight heparins (LMWHs) are important artificial preparations from heparin polysaccharide and are widely used as anticoagulant drugs. To analyze the structure and composition of LMWHs, identification and quantitation of their natural and modified building blocks are indispensable. We have established a novel reversed-phase high-performance liquid chromatography-diode array detection-electrospray ionization-mass spectrometry approach for compositional analysis of LMWHs. After being exhaustively digested and labeled with 2-aminoacridone, the structural motifs constructing LMWHs, including 17 components from dalteparin and 15 components from enoxaparin, were well separated, identified, and quantified. Besides the eight natural heparin disaccharides, many characteristic structures from dalteparin and enoxaparin, such as modified structures from the reducing end and nonreducing end, 3-O-sulfated tetrasaccharides, and trisaccharides, have been unambiguously identified based on their retention time and mass spectra. Compared with the traditional heparin compositional analysis methods, the approach described here is not only robust but also comprehensive because it is capable of identifying and quantifying nearly all components from lyase digests of LMWHs.
authors: National Glycoengineering Research Center, Shandong University, Jinan 250100, China; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
authors: Zhangjie
authors: Z
authors: Wang
authors: National Glycoengineering Research Center, Shandong University, Jinan 250100, China; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
authors: Daoyuan
authors: D
authors: Li
authors: National Glycoengineering Research Center, Shandong University, Jinan 250100, China.
authors: Xiaojun
authors: X
authors: Sun
authors: National Glycoengineering Research Center, Shandong University, Jinan 250100, China.
authors: Xue
authors: X
authors: Bai
authors: National Glycoengineering Research Center, Shandong University, Jinan 250100, China.
authors: Lan
authors: L
authors: Jin
authors: National Glycoengineering Research Center, Shandong University, Jinan 250100, China; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: lianlichi@sdu.edu.cn.
authors: Lianli
authors: L
authors: Chi
mesh_terms: D000609:Aminoacridines / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D019763:Heparin Lyase / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000032:analysis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000609:Aminoacridines; D006495:Heparin, Low-Molecular-Weight; C072515:2-aminoacridone; D019763:Heparin Lyase
keywords: AMAC derivatization; Compositional analysis; DAD; ESI–MS; LMWH