Intact Protein Mass Spectrometry for Therapeutic Protein Quantitation, Pharmacokinetics, and Biotransformation in Preclinical and Clinical Studies: An Industry Perspective

Recent advancements in immunocapture methods and mass spectrometer technology have enabled intact protein mass spectrometry to be applied for the characterization of antibodies and other large biotherapeutics from in-life studies. Protein molecules have not been traditionally studied by intact mass or screened for catabolites in the same manner as small molecules, but the landscape has changed. Researchers have presented methods that can be applied to the drug discovery and development stages, and others are exploring the possibilities of the new approaches. However, a wide variety of options for assay development exists without clear recommendation on best practice, and data processing workflows may have limitations depending on the vendor. In this perspective, we share experiences and recommendations for current and future application of mass spectrometry for biotherapeutic molecule monitoring from preclinical and clinical studies.

Automated summary

Recent advancements in immunocapture methods and mass spectrometer technology have allowed intact protein mass spectrometry to be utilized for studying antibodies and other large biotherapeutics. While researchers have introduced methods for drug discovery and development stages, there is currently a lack of clear recommendations on best practices and limitations in data processing workflows depending on the vendor. This perspective shares experiences and recommendations for the current and future application of mass spectrometry in monitoring biotherapeutic molecules in preclinical and clinical studies.