title: Quantification of human mAbs in mouse tissues using generic affinity enrichment procedures and LC-MS detection.
abstract: BACKGROUND
  The disease state can modulate the penetration of large antibody-sized therapeutic molecules into affected tissues. Suitable bioanalytical methods are required for the quantitative analysis of drug tissue levels to enable a better understanding of the parameters influencing drug penetration and target engagement.
  
  
  RESULTS
  Described is a sensitive and selective LC-MS/MS assay for the quantification of human mAb molecules in mouse tissues. By homogenizing tissues directly into serum, a common serum calibration curve can be used for multiple tissues. A generic procedure was used for affinity enrichment. An analytical range of 20 - 20,000 ng/ml was achieved in serum.
  
  
  CONCLUSIONS
  The method described here can be applied for the quantitative analysis of mAb and Fc-fusion therapeutic molecules in a variety of animal tissue matrices.
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Bogdan G
authors.initials: BG
authors.lastname: Sleczka
authors.forename: John T
authors.initials: JT
authors.lastname: Mehl
authors.forename: David J
authors.initials: DJ
authors.lastname: Shuster
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Lewis
authors.forename: Robin
authors.initials: R
authors.lastname: Moore
authors.forename: Ragini
authors.initials: R
authors.lastname: Vuppugalla
authors.forename: Surendran
authors.initials: S
authors.lastname: Rajendran
authors.forename: Celia J
authors.initials: CJ
authors.lastname: D'Arienzo
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Olah
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized / Q000032:analysis / Q000097:blood / Q000378:metabolism; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis; D012044:Regression Analysis; D012867:Skin / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014357:Trypsin / Q000378:metabolism; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010455:Peptides; D014357:Trypsin; D000069549:Ustekinumab