Drug-to-Antibody Ratio of ADC in Biological Samples by LC-MS

The drug-to-antibody ratio of antibody-drug conjugates is determined in biological samples using microflow-liquid chromatography/HRMS.

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For pharmacokinetic studies, it is necessary to quantify both the antibody and the drug on the ADC circulating in the body, because the drug bound to the antibody plays an important role in the pharmacological activity of the ADC.

ADCs in biological samples are quantified with whole antibodies using ligand binding assays such as ELISA.

However, the humanized antibodies used to bind the payload in ADCs are often derived from the human IgG subfamily, making it difficult to isolate the target ADC in biological samples such as plasma or serum.

Here, we examined species-specific differences in DAR retention when commercially available Vorsetuzumab Mc-VC-PAB-MMAE ADC (Vorsetuzumab MMAE ADC) was incubated in plasma (Human, Cynomolgus monkey , and mouse)

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