抗体偶联药物（ADC）结构复杂，且结构与作用机制相关，体内作用过程中存在多种机制相关的形式，并且可能发生时间/过程依赖性变化，因此药动学研究难度大。此外，小分子载荷的毒性较大，应特别关注脱靶、非预期释放或者代谢导致的风险或影响。采用恰当、准确可靠的分析方法表征ADC及各组成部分的药动学行为对ADC药物研究至关重要。结合ADC药物的偶联结构特点，介绍ADC药物中ADC、抗体或抗体片段、连接子和载荷等各种成分生物分析的策略及技术要点，旨在为ADC药物以及其他偶联药物的研究和研发提供一定参考。

Antibody drug conjugate (ADC) has a complex structure, which is closely related to the mechanism of action. There may be various forms of existence during the action process of ADC, and the forms of existence may be time/process dependent, bringing difficulties for pharmacokinetic research. One form of the existence is the small molecule payloads, which have obvious toxicity, and should be paid attention to the risk of off-target, unexpected release or metabolism. It is crucial to build appropriate, accurate, and reliable analysis methods to fully characterize the pharmacokinetic behavior of ADC and its corresponding components. This article introduces the strategies and key points of bioanalysis for ADC, antibody or fragment, payloads, at the early drug discovery phase, preclinical studies, and clinical trials periods during ADC drug development. This paper is hope to provide certain references for the development of ADC and other conjugate drugs.

R979.1

药品监管科学全国重点实验室课题《先进治疗药品体内过程评价方法》（2024SKLDRS0231）