Structural Characterization of the Low-Molecular-Weight Heparin Dalteparin by Combining Different Analytical Strategies

Molecules

Pauline de Wit¹  Annamaria Naggi¹  Elena Urso¹  Giangiacomo Torri¹  Antonella Bisio¹  Marco Guerrini¹ 

[1] Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, 20133 Milan, Italy;

关键词: low-molecular-weight heparin;    dalteparin;    NMR;    LC-MS;    affinity chromatography;   

DOI  :  10.3390/molecules22071051

来源: DOAJ

【 摘 要 】

A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin® by LC-MS and NMR applied both to the whole drug and to its enzymatic products. For a more in-depth approach, size homogeneous octasaccharide and decasaccharide components together with their fractions endowed with high or no affinity toward antithrombin were also isolated and their structural profiles characterized. The combination of different analytical strategies here described represents a useful tool for the assessment of batch-to-batch structural variability and for comparative evaluation of structural features of biosimilar products.

【 授权许可】

Unknown