Zheng Joanna, Mehl John, Zhu Yongxin, Xin Baomin, Olah Timothy
Bioanalytical Research, Bristol-Myers Squibb, 311 Pennington Rocky Hill Rd, Pennington, NJ 08534, USA.
Bioanalysis. 2014 Mar;6(6):859-79. doi: 10.4155/bio.14.36.
As more protein therapeutics enter the drug-discovery pipeline, the traditional ligand-binding assay (LBA) faces additional challenges to meet the rapid and diverse bioanalytical needs in the early drug-discovery stage. The high specificity and sensitivity afforded by LC-MS, along with its rapid method development, is proving invaluable for the analysis of protein therapeutics in support of drug discovery. LC-MS not only serves as a quantitative tool to complement LBA in drug discovery, it also provides structural details at a molecular level, which are used to address issues that cannot be resolved using LBA alone. This review will describe the key benefits and applications, as well as the techniques and challenges for applying LC-MS to support protein quantification in drug discovery.
随着越来越多的蛋白质治疗药物进入药物研发流程，传统的配体结合分析（LBA）在满足药物发现早期快速且多样的生物分析需求方面面临更多挑战。液相色谱-质谱联用（LC-MS）所具备的高特异性和高灵敏度，以及其快速的方法开发能力，对于支持药物发现的蛋白质治疗药物分析而言，正证明具有极高的价值。LC-MS不仅作为一种定量工具在药物发现中补充LBA，还能在分子水平提供结构细节，用于解决仅使用LBA无法解决的问题。本综述将描述应用LC-MS支持药物发现中蛋白质定量的关键优势与应用，以及相关技术和挑战。
