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Molecules 2017, 22(7), 1146;

Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin

Institute for Chemical and Biochemical Research G. Ronzoni, via G. Colombo 81, 20133 Milan, Italy
Division of Pharmaceutical Analysis, Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 645 S. Newstead Ave., St. Louis, MO 63110, USA
Author to whom correspondence should be addressed.
Received: 6 June 2017 / Revised: 30 June 2017 / Accepted: 5 July 2017 / Published: 8 July 2017
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Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses. Here, to address this issue, NMR spectroscopy and chemometrics were applied to characterize 88 crude heparin samples. The samples were also analyzed by strong anion exchange HPLC (SAX-HPLC) as an orthogonal check of the purity levels of the crudes analyzed by NMR. The HPLC data showed that the chemometric analysis of the NMR data differentiated the samples based on their purity. These orthogonal approaches differentiated samples according their glycosaminoglycan (GAG) composition and their mono and disaccharide composition and structure for each GAG family (e.g., heparin/heparan, dermatan sulfate, and chondroitin sulfate A). Moreover, quantitative HSQC and multivariate analysis (PCA) were used to distinguish between crude heparin of different animal and tissue sources. View Full-Text
Keywords: heparin; crude heparin; NMR; quantitative NMR; PCA; chemometric; HSQC heparin; crude heparin; NMR; quantitative NMR; PCA; chemometric; HSQC

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Mauri, L.; Marinozzi, M.; Mazzini, G.; Kolinski, R.E.; Karfunkle, M.; Keire, D.A.; Guerrini, M. Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin. Molecules 2017, 22, 1146.

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