Arnold Katelyn M, Capuzzi Stephen J, Xu Yongmei, Muratov Eugene N, Carrick Kevin, Szajek Anita Y, Tropsha Alexander, Liu Jian
Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
U.S. Pharmacopeia, Rockville, MD 20852, USA.
Pharmaceuticals (Basel). 2017 Jul 22;10(3):66. doi: 10.3390/ph10030066.
Enoxaparin is a low-molecular weight heparin used to treat thrombotic disorders. Following the fatal contamination of the heparin supply chain in 2007-2008, the U.S. Pharmacopeia (USP) and U.S. Food and Drug Administration (FDA) have worked extensively to modernize the unfractionated heparin and enoxaparin monographs. As a result, the determination of molecular weight (MW) has been added to the monograph as a measure to strengthen the quality testing and to increase the protection of the global supply of this life-saving drug. The current USP calibrant materials used for enoxaparin MW determination are composed of a mixture of oligosaccharides; however, they are difficult to reproduce as the calibrants have ill-defined structures due to the heterogeneity of the heparin parent material. To address this issue, we describe a promising approach consisting of a predictive computational model built from a library of chemoenzymatically synthesized heparin oligosaccharides for enoxaparin MW determination. Here, we demonstrate that this test can be performed with greater efficiency by coupling synthetic oligosaccharides with the power of computational modeling. Our approach is expected to improve the MW measurement for enoxaparin.
依诺肝素是一种用于治疗血栓性疾病的低分子量肝素。在2007 - 2008年肝素供应链发生致命污染之后，美国药典（USP）和美国食品药品监督管理局（FDA）进行了广泛努力，以使未分级肝素和依诺肝素的专论现代化。因此，分子量（MW）的测定已被添加到专论中，作为加强质量检测和增加对这种救命药物全球供应保护的一项措施。目前用于依诺肝素MW测定的USP校准材料由寡糖混合物组成；然而，由于肝素母体材料的异质性，校准物结构不明确，难以重现。为解决这一问题，我们描述了一种有前景的方法，该方法由一个基于化学酶法合成的肝素寡糖库构建的预测计算模型组成，用于依诺肝素MW的测定。在此，我们证明通过将合成寡糖与计算建模的能力相结合，可以更高效地进行该测试。我们的方法有望改进依诺肝素的MW测量。
