Heparin sodium compliance to USP monograph: structural elucidation of an atypical 2.18 ppm NMR signal

Journal of Pharmaceutical and Biomedical Analysis
Pierre A J MourierChristian Viskov

Abstract

The ¹H nuclear magnetic resonance (NMR) acceptance criteria in the new heparin US Pharmacopeia (USP) monograph do not take into account potential structural modifications responsible for any extra signals observed in ¹H NMR spectra, some purified heparins may be non-compliant under the proposed new USP guidelines and incorrectly classified as unsuitable for pharmaceutical use. Heparins from the "ES" source, containing an extra signal at 2.18 ppm, were depolymerized under controlled conditions using heparinases I, II, and III. The oligosaccharides responsible for the 2.18 ppm signal were enriched using orthogonal chromatographic techniques. After multiple purification steps, we obtained an oligosaccharide mixture containing a highly enriched octasaccharide bearing the structural modification responsible for the extra signal. Following heparinase I depolymerization, a pure tetrasaccharide containing the fingerprint structural modification was isolated for full structural determination. Using 1D and 2D ¹H NMR spectroscopy, the structural moiety responsible for the extra signal at 2.18 ppm was identified as an acetyl group on the heparin backbone, most likely resulting from a very minor manufacturing process side reaction that este...Continue Reading

References

Mar 1, 1994·Journal of Biomolecular NMR·J SchleucherC Griesinger
Nov 12, 2003·The Journal of Biological Chemistry·Charuwan ThanawiroonRobert J Linhardt
Aug 6, 2008·Journal of Pharmaceutical and Biomedical Analysis·T BeyerU Holzgrabe
Oct 15, 2010·Carbohydrate Polymers·Daniela BeccatiGanesh Venkataraman

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Citations

May 24, 2014·Journal of Pharmaceutical and Biomedical Analysis·Rubén M MaggioTeodoro S Kaufman
Jun 22, 2017·Nanomedicine·Carlos Raúl Aláez-VersónXavier Fernàndez-Busquets
Jun 22, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jan-Ytzen van der MeerLeendert J van den Bos
Dec 17, 2015·Pharmacological Reviews·Barbara MulloyClive P Page
Jun 10, 2016·Nature Biotechnology·Anita Y SzajekAli Al-Hakim
Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pierre A J Mourier

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