Bisio Antonella, Urso Elena, Guerrini Marco, de Wit Pauline, Torri Giangiacomo, Naggi Annamaria
Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, 20133 Milan, Italy.
Department of Cell and Applied Biology, Faculty of Science, Radboud University Nijmegen, 6525 HP Nijmegen, The Netherlands.
Molecules. 2017 Jun 24;22(7):1051. doi: 10.3390/molecules22071051.
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.
有多种低分子量肝素（LMWH）产品可供临床使用，尽管它们都具有相似的作用机制，但由于天然肝素的解聚过程不同，导致其药代动力学和药效学存在显著差异，因此被归类为不同的药物。虽然依诺肝素已得到广泛研究，但关于低分子量肝素达肝素的信息却很少。本研究聚焦于通过液相色谱-质谱联用（LC-MS）和核磁共振（NMR）对法安明进行详细的结构表征，该方法同时应用于整个药物及其酶解产物。为了进行更深入的研究，还分离了大小均一的八糖和十糖组分及其对抗凝血酶具有高亲和力或无亲和力的馏分，并对其结构特征进行了表征。这里描述的不同分析策略的组合是评估批次间结构变异性以及对生物类似产品结构特征进行比较评估的有用工具。
