Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin
Name
Guerrini-2009-Orthogonal analytica.pdf
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Author(s)
Sasisekharan, Ram
Guerrini, Marco
Zhang, Zhenqing
Naggi, Annamaria
Masuko, Sayaka
Casu, Casu
Linhardt, Robert J.
Torri, Giangiacomo
Shriver, Zachary H.
Langer, Robert S
Date Issued
September 2009
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Guerrini, Marco et al. “Orthogonal analytical approaches to detect potential contaminants in heparin.” Proceedings of the National Academy of Sciences 106.40 (2009): 16956 -16961.
Version
Final published version
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.
Subjects
Anticoagulant
Capillary electrophoresis
Contamination
NMR
Oversulfated chondroitin
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.0906861106
