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 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.
Bairstow
Shawn
S
Technology Resources, Baxter Healthcare, 25212 W. Illinois Rt 120, Round Lake, IL 60073, USA. shawn.bairstow@baxter.com
McKee
Jeff
J
Nordhaus
Mark
M
Johnson
Richard
R
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
D006493:Heparin; D002809:Chondroitin Sulfates