Liu Xinyue, St Ange Kalib, Lin Lei, Zhang Fuming, Chi Lianli, Linhardt Robert J
National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, and State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong 250100, China; Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, and Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States.
Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, and Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States.
J Chromatogr A. 2017 Jan 13;1480:32-40. doi: 10.1016/j.chroma.2016.12.021. Epub 2016 Dec 13.
A strategy for the comprehensive analysis of low molecular weight (LMW) heparins is described that relies on using an integrated top-down and bottom-up approach. Liquid chromatography-mass spectrometry, an essential component of this approach, is rapid, robust, and amenable to automated processing and interpretation. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues comprising a low molecular weight heparin. Using our integrated approach four different low molecular weight heparins prepared from porcine heparin through chemical β-eliminative cleavage were comprehensively analyzed. Lovenox™ and Clexane™, the innovator versions of enoxaparin marketed in the US and Europe, respectively, and two generic enoxaparins, from Sandoz and Teva, were analyzed. The results which were supported by analysis of variation (ANOVA), while showing remarkable similarities between different versions of the product and good lot-to-lot consistency of each product, also detects subtle differences that may result from differences in their manufacturing processes or differences in the source (or parent) porcine heparin from which each product is prepared.
本文描述了一种用于低分子量（LMW）肝素综合分析的策略，该策略依赖于使用自上而下和自下而上相结合的方法。液相色谱-质谱联用技术是该方法的重要组成部分，它快速、可靠，且适用于自动化处理和解读。核磁共振光谱提供了关于构成低分子量肝素的糖醛酸残基手性的补充性自上而下信息。使用我们的综合方法，对通过化学β-消除裂解从猪肝素制备的四种不同低分子量肝素进行了全面分析。分析了分别在美国和欧洲上市的依诺肝素的创新版本Lovenox™和Clexane™，以及来自山德士和梯瓦的两种通用依诺肝素。这些结果得到了方差分析（ANOVA）的支持，虽然显示出不同版本产品之间有显著相似性，且每种产品的批次间一致性良好，但也检测到了可能因其制造工艺差异或制备每种产品所用的来源（或母体）猪肝素差异而导致的细微差别。
