Inhibition of Taq polymerase as a method for screening heparin for oversulfated contaminants

Pharmacology of Heparin and Related Drugs

“…Methods for quantification and detection of OSCS include a Taq polymerase inhibition assay (Tami et al, 2008), enzyme immunoassay (Bairstow et al, 2009), and potentiometric methods (Wang and Meyerhoff, 2010) that can be developed into sensor technology (Gemene and Meyerhoff, 2010;Kang et al, 2011). Other ingenious methods for detection and quantification of OSCS in heparin include a heparinase inhibition assay (Aich et al, 2011), a convenient disposable strip-type electrochemical polyanion sensor (Kang et al, 2011), pyrolysis MS (Nemes et al, 2013), and spectropolarimetry (Chmielewski et al, 2011;Stanley et al, 2011).…”

Analysis of crude heparin by 1H NMR, capillary electrophoresis, and strong-anion-exchange-HPLC for contamination by over sulfated chondroitin sulfate

“…In response to this contamination, the FDA required nuclear magnetic resonance (NMR) spectroscopy [6] and capillary electrophoresis (CE) analysis [8] for detection of OSCS in API formulations. In addition, new proposed U.S. Pharmacopeia (www.usp.org/hottopics/heparin.html) assays include expansion of the current NMR technique and a new strong-anion-exchangehigh performance liquid chromatography (SAX-HPLC) protocol.…”

Analysis of heparin sodium by SAX/HPLC for contaminants and impurities

“…Samples of heparin were also found to contain the impurity dermatan sulfate likely present as a result of incomplete purification. NMR [8] and capillary electrophoresis [10] methods for analysis of heparin samples were quickly developed to screen heparin lots for OSCS in order to prevent further exposure to patients by contaminated heparin. Descriptions of the NMR and CE procedures are available on the Internet [11,12].…”