A new approach for heparin standardization: combination of scanning UV spectroscopy, nuclear magnetic resonance and principal component analysis

• Published in: PloS one Vol. 6; no. 1; p. e15970
• Main Authors: Lima, Marcelo A, Rudd, Timothy R, de Farias, Eduardo H C, Ebner, Lyvia F, Gesteira, Tarsis F, de Souza, Lauro M, Mendes, Aline, Córdula, Carolina R, Martins, João R M, Hoppensteadt, Debra, Fareed, Jawed, Sassaki, Guilherme L, Yates, Edwin A, Tersariol, Ivarne L S, Nader, Helena B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.01.2011; Public Library of Science (PLoS)
• Subjects: Alcohol; Analytical methods; Anticoagulants; Aromatic compounds; Biology; Chemistry; Codium isthmocladum; Computer Science; Contamination; Diagnostic imaging; Drug Contamination; Drug-Related Side Effects and Adverse Reactions; Glycosaminoglycans; Heparin; Heparin - standards; Impurities; Instrumentation; Laboratory equipment; Magnetic resonance; Magnetic resonance spectroscopy; Magnetic Resonance Spectroscopy - methods; Mathematics; Medicine; Methods; NMR; NMR spectroscopy; Nuclear engineering; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Nuclear safety; Pharmaceuticals; Poisoning; Polysaccharides; Principal Component Analysis; Principal components analysis; Reference Standards; Saccharides; Scanning; Spectrophotometry, Ultraviolet - methods; Spectroscopy; Spectrum analysis; Standardization; Brazil; Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0015970

The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA), was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities.