Laremore, T.N., Zhang, F., Dordick, J.S., Liu, J. & Linhardt, R.J. Recent progress and applications in glycosaminoglycan and heparin research. Curr. Opin. Chem. Biol. 13, 633–640 (2009).
Lindahl, U. 'Heparin'—from anticoagulant drug into the new biology. Glycoconj. J. 17, 597–605 (2000).
Petitou, M., Casu, B. & Lindahl, U. 1976-1983, a critical period in the history of heparin: the discovery of the antithrombin binding site. Biochimie 85, 83–89 (2003).
Barrowcliffe, T.W. History of heparin. Handb. Exp. Pharmacol. 2012, 3–22 (2012).
United States Pharmacopeia. Official monographs: Heparin Sodium (US 14). (1950)
Blossom, D.B. et al. Outbreak of adverse reactions associated with contaminated heparin. N. Engl. J. Med. 359, 2674–2684 (2008).
Kishimoto, T.K. et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N. Engl. J. Med. 358, 2457–2467 (2008).
McMahon, A.W. et al. Description of hypersensitivity adverse events following administration of heparin that was potentially contaminated with oversulfated chondroitin sulfate in early 2008. Pharmacoepidemiol. Drug Saf. 19, 921–933 (2010).
Guerrini, M. et al. Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat. Biotechnol. 26, 669–675 (2008).
Liu, H., Zhang, Z. & Linhardt, R.J. Lessons learned from the contamination of heparin. Nat. Prod. Rep. 26, 313–321 (2009).
United States Pharmacopeia. Official monographs: Heparin Sodium (US 32–NF27) (2011).
United States Pharmacopeia Official monographs: Heparin Sodium (US 34–NF29) (2009).
FDA Guidance for Industry. Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for Quality. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291390.pdf (June 2013).
Mulloy, B. Structure and physicochemical characterisation of heparin. Handb. Exp. Pharmacol. 2012, 77–98 (2012).
Turnbull, J.E., Hopwood, J.J. & Gallagher, J.T. A strategy for rapid sequencing of heparan sulfate and heparin saccharides. Proc. Natl. Acad. Sci. USA 96, 2698–2703 (1999).
Liu, J. & Linhardt, R.J. Chemoenzymatic synthesis of heparan sulfate and heparin. Nat. Prod. Rep. 31, 1676–1685 (2014).
Ogren, S. & Lindahl, U. Cleavage of macromolecular heparin by an enzyme from mouse mastocytoma. J. Biol. Chem. 250, 2690–2697 (1975).
Raman, K., Mencio, C., Desai, U.R. & Kuberan, B. Sulfation patterns determine cellular internalization of heparin-like polysaccharides. Mol. Pharm. 10, 1442–1449 (2013).
Keire, D.A. et al. Characterization of currently marketed heparin products: key tests for quality assurance. Anal. Bioanal. Chem. 399, 581–591 (2011).
Viskov, C. & Mourier, P. Process for oxidizing unfractionated heparins and detecting or absence of glycoserine in heparin and heparin products. US patent 0,215,519 (2005).
Mourier, P.A.J., Guichard, O.Y., Herman, F. & Viskov, C. Heparin sodium compliance to USP monograph: structural elucidation of an atypical 2.18 ppm NMR signal. J. Pharm. Biomed. Anal. 67-68, 169–174 (2012).
Lee, S.E. et al. NMR of heparin API: investigation of unidentified signals in the USP-specified range of 2.12-3.00 ppm. Anal. Bioanal. Chem. 399, 651–662 (2011).
Guerrini, M. et al. Effects on molecular conformation and anticoagulant activities of 1,6-anhydrosugars at the reducing terminal of antithrombin-binding octasaccharides isolated from low-molecular-weight heparin enoxaparin. J. Med. Chem. 53, 8030–8040 (2010).
Mazák, K., Beecher, C.N., Kraszni, M. & Larive, C.K. The interaction of enoxaparin and fondaparinux with calcium. Carbohydr. Res. 384, 13–19 (2014).
Ye, H. et al. Characterization of currently marketed heparin products: key tests for LMWH quality assurance. J. Pharm. Biomed. Anal. 85, 99–107 (2013).
Zhang, Z. et al. Analysis of pharmaceutical heparins and potential contaminants using (1)H-NMR and PAGE. J. Pharm. Sci. 98, 4017–4026 (2009).
United States Pharmacopeia. Official monographs: Heparin Sodium (US 37–NF32) (Accessed January 8, 2014).
Sommers, C.D. et al. Characterization of currently marketed heparin products: analysis of molecular weight and heparinase-I digest patterns. Anal. Bioanal. Chem. 401, 2445–2454 (2011).
Neville, G.A., Mori, F., Holme, K.R. & Perlin, A.S. Monitoring the purity of pharmaceutical heparin preparations by high-field 1H-nuclear magnetic resonance spectroscopy. J. Pharm. Sci. 78, 101–104 (1989).
Mulloy, B. et al. USP compendial methods for analysis of heparin: chromatographic determination of molecular weight distributions for heparin sodium. Anal. Bioanal. Chem. 406, 4815–4823 (2014).
Guerrini, M. et al. Antithrombin-binding octasaccharides and role of extensions of the active pentasaccharide sequence in the specificity and strength of interaction. Evidence for very high affinity induced by an unusual glucuronic acid residue. J. Biol. Chem. 283, 26662–26675 (2008).
Honchel, R. et al. A dose-response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change. Regul. Toxicol. Pharmacol. 60, 318–322 (2011).
Tami, C. et al. Inhibition of Taq polymerase as a method for screening heparin for oversulfated contaminants. Biomaterials 29, 4808–4814 (2008).
Spencer, J.A. et al. Screening of heparin API by near infrared reflectance and Raman spectroscopy. J. Pharm. Sci. 98, 3540–3547 (2009).
Trehy, M.L., Reepmeyer, J.C., Kolinski, R.E., Westenberger, B.J. & Buhse, L.F. Analysis of heparin sodium by SAX/HPLC for contaminants and impurities. J. Pharm. Biomed. Anal. 49, 670–673 (2009).
Keire, D.A. et al. Analysis of crude heparin by 1H-NMR, capillary electrophoresis, and strong-anion-exchange-HPLC for contamination by over sulfated chondroitin sulfate. J. Pharm. Biomed. Anal. 52, 921–926 (2010).
Keire, D.A., Mans, D.J., Ye, H., Kolinski, R.E. & Buhse, L.F. Assay of possible economically motivated additives or native impurities levels in heparin by 1H NMR, SAX-HPLC, and anticoagulation time approaches. J. Pharm. Biomed. Anal. 52, 656–664 (2010).
Brustkern, A.M., Buhse, L.F., Nasr, M., Al-Hakim, A. & Keire, D.A. Characterization of currently marketed heparin products: reversed-phase ion-pairing liquid chromatography mass spectrometry of heparin digests. Anal. Chem. 82, 9865–9870 (2010).
Zang, Q. et al. Combining (1)H NMR spectroscopy and chemometrics to identify heparin samples that may possess dermatan sulfate (DS) impurities or oversulfated chondroitin sulfate (OSCS) contaminants. J. Pharm. Biomed. Anal. 54, 1020–1029 (2011).
Zang, Q. et al. Class modeling analysis of heparin 1H NMR spectral data using the soft independent modeling of class analogy and unequal class modeling techniques Anal. Chem. 83, 1030–1039 (2011).
Sommers, C.D., Mans, D.J., Mecker, L.C. & Keire, D.A. Sensitive detection of oversulfated chondroitin sulfate in heparin sodium or crude heparin with a colorimetric microplate based assay. Anal. Chem. 83, 3422–3430 (2011).
Zang, Q. et al. Identification of heparin samples that contain impurities or contaminants by chemometric pattern recognition analysis of proton NMR spectral data. Anal. Bioanal. Chem. 401, 939–955 (2011).
Sommers, C.D. & Keire, D.A. Detection of possible economically motivated adulterants in heparin sodium and low molecular weight heparins with a colorimetric microplate based assay. Anal. Chem. 83, 7102–7108 (2011).
Toby, T.K., Sommers, C.D. & Keire, D.A. Detection of native chondroitin sulfate impurities in heparin sodium with a colorimetric micro-plate based assay. Anal. Methods 4, 1488–1491 (2012).
Sommers, C.D., Montpas, N., Adam, A. & Keire, D.A. Characterization of currently marketed heparin products: adverse event relevant bioassays. J. Pharm. Biomed. Anal. 67-68, 28–35 (2012).
Keire, D.A., Buhse, L.F. & al-Hakim, A. Characterization of currently marketed heparin products: composition analysis by 2D-NMR. Anal. Methods 5, 2984–2994 (2013).
Nemes, P., Hoover, W.J. & Keire, D.A. High-throughput differentiation of heparin from other glycosaminoglycans by pyrolysis mass spectrometry. Anal. Chem. 85, 7405–7412 (2013).