Oversulfated chondroitin sulfate

Guerrini, M., Beccati, D., Shriver, Z., Naggi, A., Viswanathan, K., Bisio, A., Capila, I., Lansing, J. C., Guglieri, S., Fraser, B., Al-Hakim, A., Gunay, N. S., et al. (2008). Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat. Biotechnol. 10,1-7. 

Figure 23-13 Electropherogram of heparin (30 mg/mL) spiked with oversulfated chondroitin sulfate and dermatan sulfate. Tainted heparin had 200 times more oversulfated chondroitin sulfate than shown here. [Courtesy Robert Weinberger, CE Technologies, and Todd Wielgos, Baxter Healthcare T. Wielgos, K. Havel, N. Ivanova, and R. Weinberger, J. Pharma. Biomed. Anal. 2009, 49, 319.]...

Drug contamination Adverse reactions to heparin contaminated with oversulfated chondroitin sulfate have been evaluated in a US case-control study of patients in dialysis facilities who had signs and symptoms of allergic reactions after 1 November 2007 [122 ]. There were 152 adverse reactions associated with heparin in 113 patients from 13 states from 19 November 2007 to 31 January 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions, which occurred in 100% of 21 facilities in which cases were reported versus 4.3% of 23 control facilities. Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate. Adverse reactions to the contaminated heparin were often characterized by hypotension, nausea, and shortness of breath within 30 minutes of administration. Of 130 reactions for which information on the heparin lot was available, 128 occurred in a facility that had contaminated heparin on the premises. Of 54 reactions for which the lot number of the heparin was known, 52 occurred after the administration of contaminated heparin. 

Adam, A., Montpas, N., Keire, D., Desormeaux, A., Brown, N.J., Marceau, F., Westenberger, B. Bradykinin forming capacity of oversulfated chondroitin sulfate contaminated heparin in vitro. Biomateiials 31, 5741-5748 (2010)... 

Ueoka, C. Nadanaka, S. Seno, N. Khoo, K.-H. Sugahara, K. Structural determination of novel tetra-and hexasaccharide sequences isolated from chondroitin sulfate H (oversulfated dermatan sulphate) of hagfish notochord. Glycoconjugate J. 1999, 16, 291 305. 

Figure 1. Chondroitin sulfate and dermatan sulfate are diagrammatically compared with respect to their principal disaccharide compositions. Chondroitin sulfate contains disaccharides which consist of glucuronic acid and iV-acetylgalatactosamine units, which can be variously sulfated or remain unsulfated. Most chondroitin sulfate disaccharides exist in the form of chondroitin 4-sulfate (C-4-S) or chondroitin 6-sulfate C-6-S). Unsulfated chondroitin (C-0-5) occurs as a minor constituent of most chondroitin sulfate chains. The oversulfated disaccharides, chondroitin sulfate D (CS D) and chondroitin sulfate E (CS E), are rare entities for most mammalian chondroitin sulfate chains, but appear more commonly in chondroitin sulfate chains from lower vertebrates or invertebrates. Dermatan sulfate chains are heteropolysaccharides in which the principal disaccharides are chondroitin sulfate B (CS B) units they consist of an iduronic acid and a 4-sulfated Af-acetylgalactosamine. An oversulfated version of this disaccharide (Di-di B) appears as a minor constituent in most dermatan sulfate chains. All dermatan sulfate chains contain chondroitin sulfate domains however, the size and frequency of these domains are highly regulated by cells.

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