title: Top-down and bottom-up analysis of commercial enoxaparins.
abstract: A strategy for the comprehensive analysis of low molecular weight (LMW) heparins is described that relies on using an integrated top-down and bottom-up approach. Liquid chromatography-mass spectrometry, an essential component of this approach, is rapid, robust, and amenable to automated processing and interpretation. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues comprising a low molecular weight heparin. Using our integrated approach four different low molecular weight heparins prepared from porcine heparin through chemical β-eliminative cleavage were comprehensively analyzed. Lovenox™ and Clexane™, the innovator versions of enoxaparin marketed in the US and Europe, respectively, and two generic enoxaparins, from Sandoz and Teva, were analyzed. The results which were supported by analysis of variation (ANOVA), while showing remarkable similarities between different versions of the product and good lot-to-lot consistency of each product, also detects subtle differences that may result from differences in their manufacturing processes or differences in the source (or parent) porcine heparin from which each product is prepared.
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, and State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong 250100, China; Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, and Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States. Electronic address: liux22@rpi.edu.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, and Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States. Electronic address: stangk2@rpi.edu.
authors.forename: Kalib
authors.initials: K
authors.lastname: St Ange
authors.affiliation: Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, and Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States. Electronic address: Linl5@rpi.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, and Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States. Electronic address: zhangf2@rpi.edu.
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, and State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong 250100, China. Electronic address: lianlichi@sdu.edu.cn.
authors.forename: Lianli
authors.initials: L
authors.lastname: Chi
authors.affiliation: Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, and Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States. Electronic address: linhar@rpi.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001331:Automation; D002853:Chromatography, Liquid; D016568:Drugs, Generic / Q000032:analysis / Q000737:chemistry; D017984:Enoxaparin / Q000032:analysis* / Q000737:chemistry*; D006495:Heparin, Low-Molecular-Weight / Q000032:analysis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013552:Swine; D014574:Uronic Acids / Q000032:analysis / Q000737:chemistry
chemical_list: D016568:Drugs, Generic; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D014574:Uronic Acids
keywords: Bottom-up; HILIC-ESI-FTMS; LMW heparin; NMR; Top-down