AI Article Synopsis
- The study emphasizes the necessity of using various bioanalytical methods to thoroughly evaluate the pharmacokinetics (PK) of complex bioconjugates, particularly antibody-drug conjugates (ADCs).
- A method combining immunocapture extraction and LC-MS analysis was employed to analyze the drug antibody ratio (DAR) of the ADC Tras-mcVC-PF06380101 in rats, which provided detailed profiles after different doses.
- Results showed a strong correlation between PK profiles obtained from ligand-binding assays and the calculated conjugated payload, highlighting the effectiveness of this new approach for understanding ADC metabolism and sensitivity.
Article Abstract
Aim: Complex nature of bioconjugates require multiple bioanalytical approaches to support PK and absorption, distribution, metabolism and excretion characterization. For antibody-drug conjugate (ADC) bioanalysis both LC-MS and ligand-binding assays (LBAs) are employed.
Results: A method consisting of immunocapture extraction of ADC from biomatrices followed by LC-MS analysis of light and heavy chain is described. Drug antibody ratio (DAR) profiles of ADC Tras-mcVC-PF06380101 dosed at 0.3, 1 and 3 mg/kg in Sprague Dawley rats were obtained. Combined with total antibody (monoclonal antibody) measurement by LBA, conjugated payload concentration was calculated.
Conclusion: PK profiles from LBA, ADC and calculated conjugated payload (DAR × monoclonal antibody) were in good agreement. We present a new tool for PK assessment of ADCs while also exploring ADC metabolism and DAR sensitivity of LBA ADC assay.
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| http://dx.doi.org/10.4155/bio-2016-0160 | DOI Listing |
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