Orthogonal analytical approaches to detect potential contaminants in heparin
Orthogonal analytical approaches to detect potential contaminants in heparin
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DOI：
10.1073/pnas.0906861106
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发表时间：
2009-10-06
影响因子：
11.1
通讯作者：
Sasisekharan, Ram
中科院分区：
文献类型：
--
作者：
Guerrini, Marco;Zhang, Zhenqing;Sasisekharan, Ram
肝素是一种广泛使用的抗凝剂和抗血栓剂。最近，在肝素制剂中发现了一种污染物，过硫酸化硫酸软骨素（OSCS）。肝素中OSCS的存在可能导致临床表现，最常见的是低血压和腹痛，导致数十例患者死亡。考虑到OSCS的生物学效应，一个持续关注的问题是现有方法鉴定其他也具有抗凝活性并可能引起接触系统类似激活的全磺化多糖化合物的能力。为了完成对NMR和毛细管电泳（CE）捕获肝素内更广泛的潜在污染物的能力的更广泛的分析，我们完成了对NMR（单维和二维）和CE的系统研究，以检测侧流肝素及其过磺化衍生物的各种组分。我们表明，考虑到肝素样品的复杂性，以及确保其纯度和安全性的要求，使用正交分析技术可有效检测可能存在的一系列潜在污染物。
Heparin is a widely used anticoagulant and antithrombotic agent. Recently, a contaminant, oversulfated chondroitin sulfate (OSCS), was discovered within heparin preparations. The presence of OSCS within heparin likely led to clinical manifestations, most prevalently, hypotension and abdominal pain leading to the deaths of several dozens of patients. Given the biological effects of OSCS, one continuing item of concern is the ability for existing methods to identify other persulfonated polysaccharide compounds that would also have anticoagulant activity and would likely elicit a similar activation of the contact system. To complete a more extensive analysis of the ability for NMR and capillary electrophoresis (CE) to capture a broader array of potential contaminants within heparin, we completed a systematic study of NMR, both mono-and bidimensional, and CE to detect both various components of sidestream heparin and their persulfonated derivatives. We show that given the complexity of heparin samples, and the requirement to ensure their purity and safety, use of orthogonal analytical techniques is effective at detecting an array of potential contaminants that could be present.