Identification of a simple and sensitive microplate method for the detection of oversulfated chondroitin sulfate in heparin products

Heparin is a commonly implemented anticoagulant used to treat critically in patients. Recently, a number of commercial lots of heparin products were found to be contaminated with air oversulfated chondroitin sulfate (OSCS) derivative that could elicit a hypotensive response in pigs following a single high-dose infusion. Using both contaminated heparin products and the synthetically produced derivative. we showed that the OSCS produces close-dependent hypotension in pigs. The no observed effect level (NOEL) for this contaminant appears to be approximately 1 mg/kg, corresponding to a contamination level of approximately 3%. We also demonstrated that OSCS can be identified in heparin products rising a simple, inexpensive, commercially available heparin enzyme immunoassay (ELA) kit that has a limit of detection of approximately 0.1%, well below the NOEL. This kit may provide a useful method to test heparin products for contamination with oversulfated GAG derivatives. (c) 2009 Elsevier Inc, All rights reserved.