Calculated conjugated payload from immunoassay and LC–MS intact protein analysis measurements of antibody-drug conjugate

Author:

Rago Brian1,Clark Tracey1,King Lindsay1,Zhang Jenny2,Tumey L Nathan3,Li Fengping1,Barletta Frank1,Wei Cong1,Leal Mauricio1,Hansel Steve1,Han Xiaogang14

Affiliation:

1. Pharmacokinetics, Dynamics & Metabolism, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA

2. Clinical Assay Group, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA

3. World Wide Medicinal Chemistry, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA

4. Present affiliation: PKDM Amgen, 360 Binney Street, Cambridge, MA, USA

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.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

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