Ligand-Binding Assay Development: What Do You Want to Measure Versus What You Are Measuring?

AAPS Journal

Volumn 18, Issue 2, 2016, Pages 287-289

  Mayer, Andrew P ^a,b   Hottenstein, Charles S ^a,b  

^a GLAXOSMITHKLINE   (United States)

^b DMPK   (United States)

Author keywords

characterize; free total; immunoassay; ligand binding assays

Indexed keywords

ANTIGEN; BINDING PROTEIN; MONOCLONAL ANTIBODY; DRUG; LIGAND; PROTEIN BINDING;

ANALYTIC METHOD; ARTICLE; DEAMINATION; GLYCATION; IMMUNOASSAY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLISM; OXIDATION; PROTEIN BINDING; RECEPTOR BINDING ASSAY; COMPARATIVE STUDY; HUMAN; MEDICINAL CHEMISTRY; PHYSIOLOGY; PROCEDURES;

CHEMISTRY, PHARMACEUTICAL; HUMANS; LIGANDS; PHARMACEUTICAL PREPARATIONS; PROTEIN BINDING;

EID: 84959535502     PISSN: None     EISSN: 15507416     Source Type: Journal    
DOI: 10.1208/s12248-015-9855-0     Document Type: Article

References (14)

1. Findlay JWA. Specificity and accuracy data for ligand-binding assays for macromolecules should be interpreted with caution. AAPS J. 2008;3:433–4.
2. Findlay JWA. Specificity of bioanalytical methods for pharmacokinetics support of biological macromolecular therapeutics is important. Bioanalysis. 2011;3(6):567–9.
3. Zheng J, Mehl J, Zhu Y, Xin B, Olah T. Application and challenges in using LC-MS assays for absolute quantitative analysis of therapeutic proteins in drug discovery. Bioanalysis. 2014;6(6):859–79.
4. Palandra J, Finelli A, Zhu M, Masferrer J, Neubert H. High specific and sensitive measurement of human and monkey interleukin 21 using sequential protein and tryptic peptide immunoaffinity LC-MS/MS. Anal Chem. 2013;85(11):5522–9.
5. Lee JW, Kelley M, King LE, Yang J, Salimi-Moosavi H, Tang M, et al. Bioanalytical approaches to quantify “Total” and “Free” therapeutic antibodies and their targets: technical challenges and PK/PD applications over the course of drug development. Bioanalysis. 2011;13(1):99–110.
6. Kuang B, King L, Wang HF. Therapeutic monoclonal concentration monitoring: free or total? Bioanalysis. 2010;2(6):1125–40.
7. Kelley M, Ahene AB, Gorovits B, Kamerud J, King L, McIntosh T, et al. Theoretical considerations and practical approaches to address the effect of anti-drug antibody (ADA) on quantification of biotherapeutics in circulation. AAPS J. 2013;15(3):646–58.
8. Yang J, Quarmby V. Free versus total ligand-binding assays: points to consider in biotherapeutic drug development. Bioanalysis. 2011;3(11):1163–5.
9. Heinig K, Wirz T, Schick E, Guenzi A. Bioanalysis of therapeutic peptides: differentiating between total and anti-drug antibody bound using liquid chromatography-tandem mass spectrometry quantitation. J Chromatogr A. 2013;1316:69–77.
10. Verch T, Chilewski S, Bouaraphan S, Yarovoi H, Yin KC, Chen D, et al. Pharmacokinetic immunoassay methods in the presence of soluble target. J Immunol Methods. 2010;361:75–81.
11. Williams L, Sank M, Chimalakonda A, Ni Y, Saewert M, DeSilva B, et al. Development and characterization of a free therapeutic ligand binding assay with assistance from kinetics modeling. J Immunol Methods. 2015;419:18–24.
12. Hall MP. Biotransformation and in vivo stability of protein biotherapeutics: impact on candidate selection and pharmacokinetic profiling. Drug Metab Dispos. 2014;42:1873–80.
13. Lee JW. Orthogonal tools to help determine the required selectivity of ligand-binding assays in drug development. Bioanalysis. 2014;6(8):1037–40.
14. Stevenson L, Amaravadi L, Myler H, Salazar-Fontana L, Gorovits B, Kirshner S, et al. White paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 3 – LBA and immunogenicity). Bioanalysis. 2014;6(24):3355–68.