1D and 2D-HSQC NMR: Two Methods to Distinguish and Characterize Heparin From Different Animal and Tissue Sources

Frontiers in Medicine

article

Lucio Mauri¹  Maria Marinozzi¹  Nisarga Phatak²  Michael Karfunkle²  Kalib St. Ange³  Marco Guerrini¹  David A. Keire²  Robert J. Linhardt³ 

[1] NMR Center, Istituto di Ricerche Chimiche e Biochimiche “G. Ronzoni;Division of Pharmaceutical Analysis, Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, United States;Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, United States

关键词: heparin;    NMR;    HSQC;    pharmacopeia;    animal origin;   

DOI  :  10.3389/fmed.2019.00142

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

The US Food and Drug Administration has encouraged the reintroduction of bovine heparin drug product to the US market to mitigate the risks of heparin shortages and potential adulteration or contamination of the primary source which is porcine heparin. Here, a 1D-NMR method was applied to compare heparin sodium of bovine intestinal origin with that of bovine lung, porcine, or ovine intestinal origin. The results showed that a simple 1D test using NMR signal intensity ratios among diagnostic signals of the proton spectra uniquely identified the origin of heparin and concomitantly could be used to assure the correct sample labeling. However, a limitation of the use of only mono-dimensional spectra is that these spectra may not provide sufficiently detailed information on the composition of heparin batches to adequately determine the quality of this complex product. As an alternative, a higher resolution quantitative 2D-HSQC method was used to calculate the percentage of mono- and disaccharides, distinguish the origin of heparin and, simultaneously, assess the heparin composition. The 2D-HSQC method is proposed to provide sufficient information to evaluate the quality of industrial production process used to make the drug substance. Together, the 1D and 2D data produced by these measurements can be used to assure the identity and purity of this widely used drug.

【 授权许可】

CC BY