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.
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.
Authors: Rand Jenkins; Jeffrey X Duggan; Anne-Françoise Aubry; Jianing Zeng; Jean W Lee; Laura Cojocaru; Dawn Dufield; Fabio Garofolo; Surinder Kaur; Gary A Schultz; Keyang Xu; Ziping Yang; John Yu; Yan J Zhang; Faye Vazvaei Journal: AAPS J Date: 2014-11-13 Impact factor: 4.009
Authors: Donglu Zhang; Shang-Fan Yu; Yong Ma; Keyang Xu; Peter S Dragovich; Thomas H Pillow; Luna Liu; Geoffrey Del Rosario; Jintang He; Zhonghua Pei; Jack D Sadowsky; Hans K Erickson; Cornelis E C A Hop; S Cyrus Khojasteh Journal: Drug Metab Dispos Date: 2016-07-14 Impact factor: 3.922
Authors: Mohsin El Amrani; Rick Admiraal; Lobke Willaert; Lysette J C Ebskamp-van Raaij; Amelia M Lacna; C Erik Hack; Alwin D R Huitema; Stefan Nierkens; Erik M van Maarseveen Journal: AAPS J Date: 2020-02-06 Impact factor: 4.009
Authors: Sandor Schokker; Fabrizia Fusetti; Francesco Bonardi; Remco J Molenaar; Ron A A Mathôt; Hanneke W M van Laarhoven Journal: MAbs Date: 2020 Jan-Dec Impact factor: 5.857