Spectral Service AG, Emil-Hoffmann-Straße 33, 50996, Cologne, Germany; Institute of Chemistry, Saratov State University, Astrakhanskaya Street 83, 410012, Saratov, Russia; Institute of Chemistry, Saint Petersburg State University, 13B Universitetskaya Emb., St Petersburg, 199034, Russia.
Hemostasis and Thrombosis, Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
J Pharm Biomed Anal. 2019 Sep 10;174:639-643. doi: 10.1016/j.jpba.2019.06.036. Epub 2019 Jun 27.
Heparin is a carbohydrate polymer, which is clinically used as an anticoagulant for the treatment of thrombotic disorders. The anticoagulant process is mainly mediated by the interaction of heparin with antithrombin followed by inhibition of clotting factors IIa (FIIa) and Xa (FXa). The influence of polymer disaccharide structure, average molecular weight and impurity profiling (e.g., chloride and water content) was investigated by NMR spectrometry and principal component analysis (PCA) for a representative dataset of porcine heparin samples (n = 509). A significant linear dependence was found between anticoagulant activity and scores on the third principal component (PC3) based on the non-targeted analysis of H NMR fingerprints. The correlation between average molecular values and anticoagulant activity for the 24 porcine heparin samples from two manufacturers was linear (R = 0.85) over typical values for porcine heparin preparations. Chloride and water contents were identified as negatively influencing factors for the actual activity values as their presence decrease the "pharmaceutically active" organic part of heparin preparations. Some suggestions regarding manufacturing process are made according to the results.
肝素是一种碳水化合物聚合物，临床上用作治疗血栓性疾病的抗凝剂。抗凝过程主要通过肝素与抗凝血酶的相互作用来介导，随后抑制凝血因子 IIa（FIIa）和 Xa（FXa）。通过 NMR 光谱和主成分分析（PCA）研究了多糖二糖结构、平均分子量和杂质特征（例如氯和水分含量）对代表性猪源肝素样品数据集（n=509）的影响。基于 H NMR 指纹图谱的非靶向分析，发现抗凝活性与基于第三主成分（PC3）的得分之间存在显著的线性关系。来自两个制造商的 24 个猪源肝素样品的平均分子量值与抗凝活性之间的相关性呈线性（R=0.85），超过了猪源肝素制剂的典型值。氯和水分含量被确定为实际活性值的负影响因素，因为它们的存在会降低肝素制剂中“药用活性”的有机部分。根据结果提出了一些关于制造过程的建议。
