title: Orthogonal analytical approaches to detect potential contaminants in heparin.
abstract: Heparin is a widely used anticoagulant and antithrombotic agent. Recently, a contaminant, oversulfated chondroitin sulfate (OSCS), was discovered within heparin preparations. The presence of OSCS within heparin likely led to clinical manifestations, most prevalently, hypotension and abdominal pain leading to the deaths of several dozens of patients. Given the biological effects of OSCS, one continuing item of concern is the ability for existing methods to identify other persulfonated polysaccharide compounds that would also have anticoagulant activity and would likely elicit a similar activation of the contact system. To complete a more extensive analysis of the ability for NMR and capillary electrophoresis (CE) to capture a broader array of potential contaminants within heparin, we completed a systematic study of NMR, both mono- and bidimensional, and CE to detect both various components of sidestream heparin and their persulfonated derivatives. We show that given the complexity of heparin samples, and the requirement to ensure their purity and safety, use of orthogonal analytical techniques is effective at detecting an array of potential contaminants that could be present.
authors.affiliation: Istituto di Richerche Chimiche e Biochimiche G. Ronzoni, via Giuseppe Colombo 81, 20133 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Guerrini
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zachary
authors.initials: Z
authors.lastname: Shriver
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Masuko
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Benito
authors.initials: B
authors.lastname: Casu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
authors.forename: Ram
authors.initials: R
authors.lastname: Sasisekharan
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry; D002417:Cattle; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000302:isolation & purification*; D004340:Drug Contamination / Q000517:prevention & control; D019075:Electrophoresis, Capillary / Q000379:methods*; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D013552:Swine
chemical_list: D000925:Anticoagulants; D006493:Heparin; D002809:Chondroitin Sulfates