Use of generic LC–MS/MS assays to characterize atypical PK profile of a biotherapeutic monoclonal antibody. (December 2014)

• Record Type: Journal Article
• Authors: Law, Wai Siang; Genin, Jean-Christophe; Miess, Christian; Treton, Gwenola; Warren, Andrew Paul; Lloyd, Peter; Dudal, Sherri; Krantz, Carsten
• Is Part Of: Bioanalysis. Volume 6:Number 23(2014)
• Page Start: 3225
• Page End: 3235
• Publication Date: 2014-12
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.14.167
• Languages: English
• ISSNs: 1757-6180

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.Conclusion: 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.