Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin
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; ... Show more Show less
MetadataShow full item record
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.
DepartmentHarvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Koch Institute for Integrative Cancer Research at MIT
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences (U.S.)
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.
Final published version
Anticoagulant, Capillary electrophoresis, Contamination, NMR, Oversulfated chondroitin