The past few years have witnessed enormous progresses in the development of antibody-drug conjugates(ADCs).Consequently,comprehensive analysis of ADCs in biological systems is critical in supporting discovery,developm...The past few years have witnessed enormous progresses in the development of antibody-drug conjugates(ADCs).Consequently,comprehensive analysis of ADCs in biological systems is critical in supporting discovery,development and evaluation of these agents.Liquid chromatography-mass spectrometry(LC-MS)has eme rged as a promising and versatile tool for ADC analysis across a wide range of scenarios,owing to its multiplexing ability,rapid method development,as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high,molecular resolution.However,despite this tremendous potential,challenges persist due to the high complexity in both the ADC molecules and the related biological systems.This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.展开更多
文摘The past few years have witnessed enormous progresses in the development of antibody-drug conjugates(ADCs).Consequently,comprehensive analysis of ADCs in biological systems is critical in supporting discovery,development and evaluation of these agents.Liquid chromatography-mass spectrometry(LC-MS)has eme rged as a promising and versatile tool for ADC analysis across a wide range of scenarios,owing to its multiplexing ability,rapid method development,as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high,molecular resolution.However,despite this tremendous potential,challenges persist due to the high complexity in both the ADC molecules and the related biological systems.This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.
文摘目的:建立了利用反相色谱(RP-HPLC)串联质谱对一种基于半胱氨酸偶联的抗体偶联药物(ADC)的药物抗体偶联比(DAR)进行测定的方法。方法:采用RP-HPLC方法,色谱柱为Varian公司的PLRP-S(50 mm×2.1 mm,5μm,1 000);流动相A为50 mmol·L-1磷酸钠-1.5 mol·L-1硫酸铵(p H 7.0);流动相B为75%50 mmol·L-1硫酸钠(p H 7.0)-25%异丙醇;梯度洗脱;柱温25℃;流速为0.8 m L·min-1;检测波长为280 nm。串联质谱对液相分离各组分进行定性分析。结果:所建立的RP-HPLC串联质谱分析方法可对各个峰组分进行定性定量,所测得的DAR为(4.0±0.1),标准差为2.5%。结论:基于PLRP-S色谱柱的RP-HPLC,无高浓度盐,不会对常规液相色谱系统造成污染,使用的是质谱兼容的流动相,能够兼顾质谱定性与液相定量,可用于基于半胱氨酸偶联的ADC的DAR测定。
