title: Complete Molecular Weight Profiling of Low-Molecular Weight Heparins Using Size Exclusion Chromatography-Ion Suppressor-High-Resolution Mass Spectrometry.
abstract: Low-molecular weight heparins (LMWH) prepared by partial depolymerization of unfractionated heparin are used globally to treat coagulation disorders on an outpatient basis. Patent protection for several LMWH has expired and abbreviated new drug applications have been approved by the Food and Drug Administration. As a result, reverse engineering of LMWH for biosimilar LMWH has become an active global endeavor. Traditionally, the molecular weight distributions of LMWH preparations have been determined using size exclusion chromatography (SEC) with optical detection. Recent advances in liquid chromatography-mass spectrometry methods have enabled exact mass measurements of heparin saccharides roughly up to degree-of-polymerization 20, leaving the high molecular weight half of the LMWH preparation unassigned. We demonstrate a new LC-MS system capable of determining the exact masses of complete LMWH preparations, up to dp30. This system employed an ion suppressor cell to desalt the chromatographic effluent online prior to the electrospray mass spectrometry source. We expect this new capability will impact the ability to define LMWH mixtures favorably.
authors.affiliation: Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University Medical Campus , 670 Albany Street, Boston, Massachusetts 02118, United States.|Bioinformatics Program, Boston University , Boston, Massachusetts 02115, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zaia
authors.affiliation: Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University Medical Campus , 670 Albany Street, Boston, Massachusetts 02118, United States.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Khatri
authors.affiliation: Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University Medical Campus , 670 Albany Street, Boston, Massachusetts 02118, United States.|Bioinformatics Program, Boston University , Boston, Massachusetts 02115, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Klein
authors.affiliation: Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University Medical Campus , 670 Albany Street, Boston, Massachusetts 02118, United States.
authors.forename: Chun
authors.initials: C
authors.lastname: Shao
authors.affiliation: Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University Medical Campus , 670 Albany Street, Boston, Massachusetts 02118, United States.
authors.forename: Yuewei
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Thermo Fisher Scientific , San Jose, California 95134, United States.
authors.forename: Rosa
authors.initials: R
authors.lastname: Viner
mesh_terms: D064753:Ammonium Hydroxide / Q000737:chemistry; D059451:Biosimilar Pharmaceuticals / Q000032:analysis* / Q000737:chemistry; D002850:Chromatography, Gel / Q000379:methods*; D017985:Dalteparin / Q000032:analysis* / Q000737:chemistry; D017984:Enoxaparin / Q000032:analysis* / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D008970:Molecular Weight
chemical_list: D059451:Biosimilar Pharmaceuticals; D017984:Enoxaparin; D064753:Ammonium Hydroxide; D017985:Dalteparin