title: Use of generic LC-MS/MS assays to characterize atypical PK profile of a biotherapeutic monoclonal antibody.
abstract: BACKGROUND
  The fully human monoclonal antibody mAb123, which binds to and neutralizes chemokine motif ligand-21 (CCL21) displays a faster clearance in cynomolgus monkey compared with typical IgG kinetics. A direct and an immunoaffinity LC-MS/MS assays were developed to compare with the previously established ligand-binding assays (LBAs).
  
  
  RESULTS
  A strong correlation of LC-MS/MS pharmacokinetic data with LBA data confirmed the rapid drug disposition of mAb123 is an intrinsic property of the molecule, rather than interference of anti-mAb123 antibodies in the LBA.
  
  
  CONCLUSIONS
  The data illustrate that in cases of unexpected results from LBA, application of orthogonal bioanalytical techniques such as LC-MS/MS can help in in interpretation of pharmacokinetic as determined by LBAs.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics Biologics, Novartis Institute for Biomedical Research, Novartis, Basel, Switzerland.
authors.forename: Wai Siang
authors.initials: WS
authors.lastname: Law
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Genin
authors.forename: Christian
authors.initials: C
authors.lastname: Miess
authors.forename: Gwenola
authors.initials: G
authors.lastname: Treton
authors.forename: Andrew Paul
authors.initials: AP
authors.lastname: Warren
authors.forename: Peter
authors.initials: P
authors.lastname: Lloyd
authors.forename: Sherri
authors.initials: S
authors.lastname: Dudal
authors.forename: Carsten
authors.initials: C
authors.lastname: Krantz
mesh_terms: D053000:Analytic Sample Preparation Methods; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008024:Ligands; D016014:Linear Models; D008252:Macaca fascicularis; D059346:Magnets; D008863:Microspheres; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D008024:Ligands