Analysis of pharmaceutical heparins and potential contaminants using 1H-NMR and PAGE
Authors
Zhang, Zhenqing
Li, Boyangzi
Suwan, Jiraporn
Zhang, Fuming
Wang, Zhenyu
Liu, Haiying
Mulloy, Barbara
Linhardt, Robert J.
ORCID
https://orcid.org/0000-0003-2219-5833
No Thumbnail Available
Other Contributors
Issue Date
2009-01-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
Full Citation
Analysis of pharmaceutical heparins and potential contaminants using 1H-NMR and PAGE, Z. Zhang, B. Li, J. Suwan, F. Zhang, Z. Wang, H. Liu, B. Mulloy, R. J. Linhardt, Journal of Pharmaceutical Science, 98, 4017-4026, 2009.
Abstract
In 2008, heparin (active pharmaceutical ingredient, API) lots were associated with anaphylactoid-type reactions. Oversulfated chondroitin sulfate (OSCS), a semi-synthetic glycosaminoglycan (GAG), was identified as a contaminant and dermatan sulfate (DS) as an impurity. While DS has no known toxicity, OSCS was toxic leading to patient deaths. Heparins, prepared before these adverse reactions, needed to be screened for impurities and contaminants. Heparins were analyzed using high-field (1)H-NMR spectroscopy. Heparinoids were mixed with a pure heparin and analyzed by (1)H-NMR to assess the utility of (1)H-NMR for screening heparin adulterants. Sensitivity of heparinoids to deaminative cleavage, a method widely used to depolymerize heparin, was evaluated with polyacrylamide gel electrophoresis to detect impurities and contaminants, giving limits of detection (LOD) ranging from 0.1% to 5%. Most pharmaceutical heparins prepared between 1941 and 2008 showed no impurities or contaminants. Some contained DS, CS, and sodium acetate impurities. Heparin prepared in 2008 contained OSCS contaminant. Heparin adulterated with heparinoids showed additional peaks in their high-field (1)H-NMR spectra, clearly supporting NMR for monitoring of heparin API with an LOD of 0.5-10%. Most of these heparinoids were stable to nitrous acid treatment suggesting its utility for evaluating impurities and contaminants in heparin API.
Description
Journal of Pharmaceutical Science, 98, 4017-4026
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Journal of Pharmaceutical Sciences
https://harc.rpi.edu/
Rensselaer Polytechnic Institute, Troy, NY
Journal of Pharmaceutical Sciences
https://harc.rpi.edu/
Access
https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1002/jps.21729