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. 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.