School of Pharmacy, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
Int J Pharm. 2011 Sep 30;417(1-2):70-82. doi: 10.1016/j.ijpharm.2010.12.010. Epub 2010 Dec 13.
The development and quality assessment of modern biopharmaceuticals, particularly protein and peptide drugs, requires an array of analytical techniques to assess the integrity of the bioactive molecule during formulation and administration. Mass spectrometry is one of these methods and is particularly suitable for determining chemical modifications of protein and peptide drugs. The emphasis of this review is the identification of covalent interactions between protein and peptide bioactives with polymeric pharmaceutical formulations using mass spectrometry with the main focus on matrix-assisted laser desorption/ionization (MALDI) coupled tandem time-of-flight (TOF/TOF) mass spectrometry (MS). The basics of MALDI TOF MS and collision-induced dissociation (CID)-based ion fragmentation will be explained and applications for qualitative characterization of protein and peptide drugs and their interactions with pharmaceutical polymers will be discussed using three case studies.
现代生物制药（尤其是蛋白质和肽类药物）的开发和质量评估需要一系列分析技术，以在制剂和给药过程中评估生物活性分子的完整性。质谱法就是其中一种方法，特别适合于确定蛋白质和肽类药物的化学修饰。本综述的重点是使用质谱法（主要是基质辅助激光解吸/电离（MALDI）串联飞行时间（TOF/TOF）质谱法（MS））鉴定蛋白质和肽类生物活性物质与聚合物药物制剂之间的共价相互作用。本文将解释 MALDI-TOF-MS 的基础知识和基于碰撞诱导解离（CID）的离子碎片化，并使用三个案例研究讨论其在蛋白质和肽类药物的定性特征及其与药物聚合物相互作用方面的应用。
