Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin
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 l...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2010
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| Online Access: | http://hdl.handle.net/1721.1/58300 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0003-4255-0492 |
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| author | Sasisekharan, Ram Guerrini, Marco Zhang, Zhenqing Naggi, Annamaria Masuko, Sayaka Casu, Casu Linhardt, Robert J. Torri, Giangiacomo Shriver, Zachary H. Langer, Robert S |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Sasisekharan, Ram Guerrini, Marco Zhang, Zhenqing Naggi, Annamaria Masuko, Sayaka Casu, Casu Linhardt, Robert J. Torri, Giangiacomo Shriver, Zachary H. Langer, Robert S |
| author_sort | Sasisekharan, Ram |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:36:52Z |
| format | Article |
| id | mit-1721.1/58300 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:36:52Z |
| publishDate | 2010 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/583002022-09-27T20:43:17Z Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin Sasisekharan, Ram Guerrini, Marco Zhang, Zhenqing Naggi, Annamaria Masuko, Sayaka Casu, Casu Linhardt, Robert J. Torri, Giangiacomo Shriver, Zachary H. Langer, Robert S 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 Sasisekharan, Ram Shriver, Zachary Langer, Robert Sasisekharan, Ram Anticoagulant Capillary electrophoresis Contamination NMR Oversulfated chondroitin 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. National Institutes of Health (U.S.) (Grants GM 57073 and HL59966 ) 2010-09-03T14:27:42Z 2010-09-03T14:27:42Z 2009-09 2009-06 Article http://purl.org/eprint/type/JournalArticle 0027-8424 http://hdl.handle.net/1721.1/58300 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. 19805108 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.0906861106 Proceedings of the National Academy of Sciences of the United States of America 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. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Anticoagulant Capillary electrophoresis Contamination NMR Oversulfated chondroitin Sasisekharan, Ram Guerrini, Marco Zhang, Zhenqing Naggi, Annamaria Masuko, Sayaka Casu, Casu Linhardt, Robert J. Torri, Giangiacomo Shriver, Zachary H. Langer, Robert S Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin |
| title | Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin |
| title_full | Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin |
| title_fullStr | Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin |
| title_full_unstemmed | Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin |
| title_short | Orthogonal Analytical Approaches to Detect Potential Contaminants in Heparin |
| title_sort | orthogonal analytical approaches to detect potential contaminants in heparin |
| topic | Anticoagulant Capillary electrophoresis Contamination NMR Oversulfated chondroitin |
| url | http://hdl.handle.net/1721.1/58300 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0003-4255-0492 |
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