title: Mapping of low molecular weight heparins using reversed phase ion pair liquid chromatography-mass spectrometry.
abstract: Low molecular weight heparins (LMWHs) are structurally complex, highly sulfated and negatively charged, linear carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. They are widely used as anticoagulant drugs possessing better bioavailability, longer half-life, and lower side effects than heparin. Comprehensive structure characterization of LMWHs is important for drug quality assurance, generic drug application, and new drug research and development. However, fully characterization of all oligosaccharide chains in LMWHs is not feasible for current available analytical technologies due to their structure complexity and heterogeneity. Fingerprinting profiling is an efficient way for LMWHs' characterization and comparison. In this work, we present a simple, sensitive, and powerful analytical approach for structural characterization of LMWHs. Two different LMWHs, enoxaparin and nadroparin, were analyzed using reversed phase ion pair electrospray ionization mass spectrometry (RPIP-ESI-MS). More than 200 components were identified, including major structures, minor structures, and process related impurities. This approach is robust for high resolution and complementary fingerprinting analysis of LMWHs.
authors.affiliation: National Glycoengineering Research Center, Shandong University, Jinan 250100, China; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
authors.forename: Daoyuan
authors.initials: D
authors.lastname: Li
authors.forename: Lequan
authors.initials: L
authors.lastname: Chi
authors.forename: Lan
authors.initials: L
authors.lastname: Jin
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Xuzhao
authors.initials: X
authors.lastname: Du
authors.forename: Shengli
authors.initials: S
authors.lastname: Ji
authors.forename: Lianli
authors.initials: L
authors.lastname: Chi
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000302:isolation & purification; D002240:Carbohydrate Sequence; D056148:Chromatography, Reverse-Phase; D017984:Enoxaparin / Q000737:chemistry* / Q000302:isolation & purification; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D017762:Nadroparin / Q000737:chemistry* / Q000302:isolation & purification; D013552:Swine
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D017762:Nadroparin
keywords: Chain mapping; Low molecular weight heparin; Mass spectrometry; Reversed phase ion pair