U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Division of Pharmaceutical Analysis, 645 S. Newstead Ave., St. Louis, MO, 63110, USA.
Pfizer Inc., Chesterfield, MO, USA.
J Am Soc Mass Spectrom. 2016 May;27(5):822-33. doi: 10.1007/s13361-016-1369-1. Epub 2016 Mar 17.
Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics. Graphical Abstract ᅟ.
分析技术能够检测结构变化，对于监测单克隆抗体药物产品的质量是必要的。离子淌度质谱提供了一种先进的蛋白质高级结构特征分析模式。在这项工作中，我们评估了离子淌度质谱测量和淌度图谱的重现性，以及该方法区分和/或表征不同单克隆抗体药物产品的适用性。在分析的多天窗口内，确定了四个可重现的淌度图谱衍生指标。这些指标进一步应用于不同 IgG 亚类、制造商和批次的单克隆抗体药物产品的比较研究。基于离子淌度质谱淌度图谱衍生的四个指标，这些比较产生了一些差异。使用碰撞诱导解折叠导致了更多的观察到的差异。使用总和电荷状态数据集和漂移时间以外的指标分析，允许在不同的单克隆抗体药物产品之间进行更全面的比较研究。离子淌度质谱能够检测具有相同靶蛋白但不同生产技术的单克隆抗体之间的差异，以及具有不同靶标的产品之间的差异。这些差异并不总是通过传统的碰撞截面研究来检测到。离子淌度质谱，以及碰撞诱导解折叠的附加分离能力，具有高度重现性，仍然是蛋白质治疗剂高级分析特征的有前途的技术。
