title: Identification of a simple and sensitive microplate method for the detection of oversulfated chondroitin sulfate in heparin products.
abstract: Heparin is a commonly implemented anticoagulant used to treat critically ill patients. Recently, a number of commercial lots of heparin products were found to be contaminated with an 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 dose-dependent hypotension in pigs. The no observed effect level (NOEL) for this contaminant appears to be approximately 1mg/kg, corresponding to a contamination level of approximately 3%. We also demonstrated that OSCS can be identified in heparin products using a simple, inexpensive, commercially available heparin enzyme immunoassay (EIA) 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.
authors.affiliation: Technology Resources, Baxter Healthcare, 25212 W. Illinois Rt 120, Round Lake, IL 60073, USA. shawn.bairstow@baxter.com
authors.forename: Shawn
authors.initials: S
authors.lastname: Bairstow
authors.forename: Jeff
authors.initials: J
authors.lastname: McKee
authors.forename: Mark
authors.initials: M
authors.lastname: Nordhaus
authors.forename: Richard
authors.initials: R
authors.lastname: Johnson
mesh_terms: D000818:Animals; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000032:analysis* / Q000633:toxicity; D004340:Drug Contamination; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis*; D007022:Hypotension / Q000139:chemically induced; D007124:Immunoenzyme Techniques; D009682:Magnetic Resonance Spectroscopy; D013552:Swine
chemical_list: D006493:Heparin; D002809:Chondroitin Sulfates