Method to Detect Contaminants in Heparin Using Radical Depolymerization and Liquid Chromatography–Mass Spectrometry

• Published in: Analytical chemistry (Washington) Vol. 86; no. 1; pp. 326 - 330
• Main Authors: Li, Guoyun, Cai, Chao, Li, Lingyun, Fu, Li, Chang, Yuqing, Zhang, Fuming, Toida, Toshihiko, Xue, Changhu, Linhardt, Robert J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.01.2014
• Subjects: adulterated products; adverse effects; Analytical chemistry; Animals; Anticoagulants; Chemical contaminants; chondroitin sulfate; Chondroitin Sulfates - analysis; Chondroitin Sulfates - metabolism; Chromatography; Chromatography, Liquid - methods; Contaminants; death; depolymerization; Drug Contamination; heparan sulfate; heparin; Heparin - analysis; Heparin - metabolism; Heparins; Liquid chromatography; Liquids; Mass spectrometry; Mass Spectrometry - methods; Polymerization; Radicals; Spectrometry; Spectroscopy; Sulfates; Swine
• ISSN: 0003-2700; 1520-6882; 1520-6882
• DOI: 10.1021/ac403625a

Heparin is a critically important anticoagulant drug that was contaminated with a persulfonated polysaccharide in 2008, resulting in a number of severe adverse reactions, some leading to death. Controversy remains as to the precise composition of the 2008 contaminant, and new information suggests that heparin may now be subject to adulteration with a new, difficult to detect, contaminant, N-sulfo oversulfated chondroitin sulfate. This study synthesizes this new potential contaminant and describes the use of radical depolymerization followed by liquid chromatography–mass spectrometry to detect N-sulfo oversulfated chondroitin sulfate and to confirm the structure of the 2008 contaminant as oversulfated chondroitin sulfate and not oversulfated heparan sulfate.