Bottom-up sample preparation for the LC–MS/MS quantification of anti-cancer monoclonal antibodies in bio matrices

Therapeutic monoclonal antibodies (mAbs) are rapidly taking over the treatment of many malignancies, and an astonishing number of mAbs is in development. This causes a high demand for quantification of mAbs in biomatrices both for measuring therapeutic mAb concentrations and to support pharmacokinet...

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Veröffentlicht in:Bioanalysis 2020-10, Vol.12 (19), p.1405-1425
Hauptverfasser: de Jong, Karen Am, van Breugel, Suse J, Hillebrand, Michel Jx, Rosing, Hilde, Huitema, Alwin Dr, Beijnen, Jos H
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Sprache:eng
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Zusammenfassung:Therapeutic monoclonal antibodies (mAbs) are rapidly taking over the treatment of many malignancies, and an astonishing number of mAbs is in development. This causes a high demand for quantification of mAbs in biomatrices both for measuring therapeutic mAb concentrations and to support pharmacokinetics and pharmacodynamics studies. Conventionally, ligand-binding assays are used for these purposes, but LC–MS is gaining popularity. Although intact (top-down) and subunit (middle-down) mAb quantification is reported, signature peptide (bottom-up) quantification is currently most advantageous. This review provides an overview of the reported bottom-up mAb quantification methods in biomatrices as well as general recommendations regarding signature peptide and internal standard selection, reagent use and optimization of digestion in bottom-up quantification methods.
ISSN:1757-6180
1757-6199
DOI:10.4155/bio-2020-0204