a Department of Biochemistry and Molecular Biology , University of Nebraska Medical Center , Omaha , Nebraska , USA.
b Eppley Institute for Research in Cancer and Allied Diseases and Buffett Cancer Center , University of Nebraska Medical Center , Omaha , Nebraska , USA.
Expert Rev Proteomics. 2018 Jun;15(6):503-513. doi: 10.1080/14789450.2018.1480110. Epub 2018 May 31.
Structural characterization of low molecular weight heparin (LMWH) is critical to meet biosimilarity standards. In this context, the review focuses on structural analysis of labile sulfates attached to the side-groups of LMWH using mass spectrometry. A comprehensive review of this topic will help readers to identify key strategies for tackling the problem related to sulfate loss. At the same time, various mass spectrometry techniques are presented to facilitate compositional analysis of LMWH, mainly enoxaparin. Areas covered: This review summarizes findings on mass spectrometry application for LMWH, including modulation of sulfates, using enzymology and sample preparation approaches. Furthermore, popular open-source software packages for automated spectral data interpretation are also discussed. Successful use of LC/MS can decipher structural composition for LMWH and help evaluate their sameness or biosimilarity with the innovator molecule. Overall, the literature has been searched using PubMed by typing various search queries such as 'enoxaparin', 'mass spectrometry', 'low molecular weight heparin', 'structural characterization', etc. Expert commentary: This section highlights clinically relevant areas that need improvement to achieve satisfactory commercialization of LMWHs. It also primarily emphasizes the advancements in instrumentation related to mass spectrometry, and discusses building automated software for data interpretation and analysis.
结构表征对满足低分子肝素(LMWH)的生物相似性标准至关重要。在这方面,本综述重点关注使用质谱法对 LMWH 侧链上不稳定硫酸酯进行的结构分析。对这一主题的全面回顾将帮助读者确定解决与硫酸酯丢失相关问题的关键策略。同时,还介绍了各种质谱技术,以促进 LMWH(主要是依诺肝素)的组成分析。
本综述总结了用于 LMWH 的质谱应用的发现,包括使用酶学和样品制备方法对硫酸酯进行调制。此外,还讨论了用于自动光谱数据分析的流行开源软件包。成功使用 LC/MS 可以解析 LMWH 的结构组成,并有助于评估其与创新分子的相同性或生物相似性。总体而言,使用 PubMed 搜索文献,输入各种搜索查询,如“依诺肝素”、“质谱”、“低分子肝素”、“结构表征”等。
本节重点介绍了需要改进的临床相关领域,以实现 LMWH 的满意商业化。它还主要强调了与质谱相关的仪器设备的进步,并讨论了用于数据解释和分析的自动化软件的构建。