title: An exploratory universal LC-MS/MS assay for bioanalysis of hinge region-stabilized human IgG4 mAbs in clinical studies.
abstract: BACKGROUND
  Due to the increasing number of monoclonal antibody (mAb) drug candidates entering clinical development, bioanalytical laboratories can benefit from generic liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays capable of quantifying a variety of human mAb-based therapeutic drug candidates in plasma/serum samples from clinical studies.
  
  
  RESULTS
  We have developed and evaluated an exploratory LC-MS/MS assay capable of quantifying hinge region-stabilized IgG4 therapeutic mAb drugs and drug candidates in clinical samples. The exploratory assay is based upon a single 'universal IgG4' surrogate peptide.
  
  
  CONCLUSIONS
  The novel exploratory LC-MS/MS assay reported herein, upon further refinement and full validation, is predicted to enable bioanalytical scientists to quantify all hinge region-stabilized human IgG4 therapeutic mAbs in human studies without having to develop a new assay for every new stabilized IgG4 mAb entering clinical development.
authors.affiliation: Bristol-Myers Squibb, R&D, Route 206 & Province Line Road, Princeton, NJ 08543, USA. mfurlong@amicusrx.com.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Furlong
authors.forename: Craig
authors.initials: C
authors.lastname: Titsch
authors.forename: Weifeng
authors.initials: W
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jemal
authors.forename: Jianing
authors.initials: J
authors.lastname: Zeng
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D017434:Protein Structure, Tertiary; D053719:Tandem Mass Spectrometry / Q000592:standards; D014357:Trypsin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D010455:Peptides; D014357:Trypsin