Affiliation:
1. Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
Abstract
Background: Combination therapies with monoclonal antibodies (mAbs) enhance therapeutic activity and may circumvent drug resistance. However, these studies present bioanalytical challenges for ligand-binding assays (LBAs). Recent MS-based protein quantification offers an alternative for bioanalysis. Results: A hybrid LC–MS/MS assay was developed to simultaneously measure human serum concentrations of two mAbs. Anti-idiotypic reagents that did not work in LBAs were successfully used for mAb affinity capture enrichment. Stable isotope-labeled peptide internal standards were employed. The mAb quantification involved measuring a signature CDR peptide derived from each mAb as a surrogate. Selected clinical samples were successfully analyzed. Conclusion: The multiplexed LC–MS/MS method provided a powerful quantitative tool for clinical PK assessment of co-administered mAbs without the requirement for stringent affinity capture reagents.
Subject
Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry
Cited by
58 articles.
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