抗体偶联药物分析方法的概述及进展

单克隆抗体药物的靶点选择性非常高，但其药理活性普遍比较低。近年来抗体偶联药物（antibodydrugconjugate，ADC）的出现，正好弥补了单克隆抗体药物的缺点。ADC 是一类通过化学偶联子将单克隆抗体和不同数目的小分子细胞毒素（效应分子）偶联起来的药物。这种新型的药物结合了单克隆抗体的高特异性和小分子毒素的高活性。ADC 药物的分析工作非常困难和费时，主要归因于分析物的多样性及分析方法的复杂性。本文将对目前在ADC 药物研究的不同方面如理化性质表征、药代动力学和药效学研究、以及免疫原性评价等所用的分析方法做出归纳和阐述，并讨论这些方法所面临的困难和挑战。

Monoclonal antibodies (mAb)usually possess high target selectivity but low potency,as compared to small cytotoxic molecules. Recently,a novel type of therapeutics has emerged,named antibody-drug conjugates (ADC),which may overcome the drawback of mAb therapeutics. An ADC molecule is composed of an mAb molecule and a varying number of small-molecule cytotoxin moieties conjugated through chemical linkers, combining high target specificity of the mAb and highly potent cell killing activity of the toxin. Due to the multiplexity of analytes and complexity of analytical methods,analytical work for ADC is very challenging and time-consuming. This review summarized the analytical strategies and methods used in physicochemical property characterizations,pharmacokinetic studies and immunogenicity assessments of ADCs,and discussed the potential challenges associated with these approaches.