title: PK assays for antibody-drug conjugates: case study with ado-trastuzumab emtansine.
abstract: BACKGROUND
  Antibody-drug conjugates (ADCs) combine the characteristics of large-molecule biologics and small-molecule drugs and are heterogeneous mixtures that can biotransform in vivo, resulting in additional complexity. ADC bioanalytical strategies require novel analytical methods, as well as existing large- and small-molecule methods. Because ADCs in late-stage clinical development are relatively new, regulatory guidelines and standard industry best practices for developing strategies for bioanalytical PK assays are still being established.
  
  
  RESULTS
  A PK assay strategy was developed that included comprehensive novel reagent and assay characterization approaches for the ADC ado-trastuzumab emtansine (T-DM1).
  
  
  CONCLUSIONS
  The bioanalytical strategy was successfully applied to the drug development of T-DM1 and ensured that key analytes were accurately measured in support of nonclinical and clinical development.
authors: Department of Bioanalytical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080-4990, USA. dere.randall@gene.com
authors: Randall
authors: R
authors: Dere
authors: Joo-Hee
authors: JH
authors: Yi
authors: Corinna
authors: C
authors: Lei
authors: Ola M
authors: OM
authors: Saad
authors: Catherine
authors: C
authors: Huang
authors: Yanhong
authors: Y
authors: Li
authors: Jakub
authors: J
authors: Baudys
authors: Surinder
authors: S
authors: Kaur
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D018796:Immunoconjugates / Q000032:analysis* / Q000493:pharmacokinetics; D013058:Mass Spectrometry; D008453:Maytansine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018796:Immunoconjugates; D008453:Maytansine; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine