title: A multiplexed hybrid LC-MS/MS pharmacokinetic assay to measure two co-administered monoclonal antibodies in a clinical study.
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.
  
  
  CONCLUSIONS
  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.affiliation: Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Keyang
authors.initials: K
authors.lastname: Xu
authors.forename: Luna
authors.initials: L
authors.lastname: Liu
authors.forename: Mauricio
authors.initials: M
authors.lastname: Maia
authors.forename: Jenny
authors.initials: J
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Lowe
authors.forename: An
authors.initials: A
authors.lastname: Song
authors.forename: Surinder
authors.initials: S
authors.lastname: Kaur
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000378:metabolism; D007553:Isotope Labeling; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000737:chemistry / Q000592:standards; D011786:Quality Control; D011994:Recombinant Proteins / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000911:Antibodies, Monoclonal; D007147:Immunoglobulin Light Chains; D010455:Peptides; D011994:Recombinant Proteins