A generic approach for simultaneous measurements of total antibody and cleavable antibody-conjugated drug by LC/MS/MS.

Anal Biochem

Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA 02139, USA. Electronic address:

Published: November 2017

The current industry practice for antibody-drug conjugate (ADC) bioanalysis includes quantification of total antibody and antibody-conjugated drug. Here, we report a novel 2-in-1 approach for measuring total antibody and protease-cleavable conjugated drug Monomethyl Auristatin E (MMAE) concurrently. This allows for the determination of the DAR (Drug Antibody Ratio) for in vivo samples, with a 3-orders linear range based on total antibody concentration from 0.1 to 100 μg/mL. Our generic, concurrent method has been cross-validated with the previously established methods in an animal study. This novel approach is applicable to all human IgG1 ADCs with papain cleavable conjugated drug in preclinical studies.

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http://dx.doi.org/10.1016/j.ab.2017.08.024DOI Listing

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