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Reply to Oversulfated chondroitin sulfate is not the sole contaminant in heparin

Nature Biotechnology volume 28, pages 207–211 (2010)Cite this article

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Marco Guerrini, Zachary Shriver, Annamaria Naggi, Benito Casu, Robert J Linhardt, Giangiacomo Torri & Ram Sasisekharan reply:

Our paper in Nature Biotechnology reported the structural identification of a major contaminant in suspect heparin lots1. Notably, the structural assignment of oversulfated chondroitin sulfate (OSCS) was made by four independent laboratories (and has since been confirmed by others2,3). In their conclusion and in agreement with our original findings, Pan et al. conclude that OSCS is an important contaminant in heparin. The identification of OSCS as a major contaminant within heparin has had a number of ramifications, including providing an underlying logic for the original screening methods developed by the FDA and since implemented into pharmacopeias. Widespread adoption of such methods as screening tools has helped secure the heparin supply and, most importantly, decreased to baseline adverse reactions associated with administration of heparin.

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Figure 1: Comparison of the proton NMR spectra of synthesized OSCS at pH 7 and pH 5.
Figure 2: NMR spectra of sulfated chondroitins.
Figure 3: Two-dimensional HSQC analysis of a 10% wt/wt mixture of sulfated chondroitin (ds = 3.1) in heparin compared to a reference standard of sulfated chondroitin.
Figure 4: Two-dimensional HSQC analysis of oversulfated heparin waste compared to authentic heparin.

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Acknowledgements

The authors thank G. Cassinelli, M. Nasr and L. Buhse for discussions and the US National Institutes of Health for grant HL101721 to R.S. and R.J.L. to support this work.

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  1. The Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA

    Jing Pan, Yi Qian, Xiaodong Zhou, Andrew Pazandak, Sarah B Frazier, Peter Weiser, Hong Lu & Lijuan Zhang

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Correspondence to Lijuan Zhang.

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Competing interests

R.S. is a director of Momenta Pharmaceuticals, Z.S. reports receiving consulting fees from Momenta Pharmaceuticals and R.J.L. is a paid consultant for Baxter Pharmaceuticals.

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Pan, J., Qian, Y., Zhou, X. et al. Reply to Oversulfated chondroitin sulfate is not the sole contaminant in heparin. Nat Biotechnol 28, 207–211 (2010). https://doi.org/10.1038/nbt0310-207

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