2024 - Hybrid LC-MS/MS Technology Becoming the New Norm in the Bioanalysis of Antibody-Drug Conjugates – Examples and Case Studies

Recently, the role of hybrid liquid chromatography-mass spectrometry (LC-MS/MS) in the analysis of antibody-drug conjugates has increased due to the complexity and number of bioanalytical assays needed to support this modality in the drug development process. Antibody-drug conjugates tend to consist of a toxic small molecule payload attached via a linker to an antibody. The application of these drugs had mainly been in oncology where their mode of action is for the antibody to attach at the desired target site with subsequent release of the small molecule to combat tumor cells.
Recently, a much wider application or use of “ADCs” to other modalities such as antibody-peptide conjugates, antibody-RNA conjugates (ARCs) or even other more complicated multi-functional entities has been reported. Traditionally, LC-MS/MS has mainly been applied to the quantitation of the small molecule payload or the linker moiety. Ligand-binding assays are highly successful for the quantitation of the total antibody and sometimes may be suitable for the quantification of intact antibody-drug conjugates.
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In many preclinical cases, “generic” methods that make the method development and analysis much quicker and more cost-effective are used. At the very least, the availability of hybrid LC-MS/MS as an alternative technology greatly increases the chances of success in the bioanalysis of antibody-drug conjugates.
Hybrid LC-MS/MS is proving to be an increasingly valuable tool for delivering answers about complex analytes such as antibody-drug conjugates to enhance the drug development process. Register for this webinar today to get an overview of the bioanalysis of antibody-drug conjugates.
Keywords: Drug Development, Biologics, Biotech, CRO, Biosimilars, Bioanalytical, Mass Spectrometry, Laboratory Technology, Liquid Chromatography, Antibody-Drug Conjugate, Bioanalytical Testing, CDMO/CMO, Basic Research