Traditionally, ligand-binding assays are the golden standard for the quantitative analysis of therapeutic proteins in biological matrices. However, assay development can be rather time-consuming, the dynamic range is limited and selectivity issues are not unusual in ligand-binding assays. Therefore, bioanalytical methods for therapeutic proteins using LC-MS can provide a useful alternative. Potential advantages are the faster method development time, the increased linear dynamic range, higher selectivity and the easy-to-implement multiplex methods.
TNO Triskelion offers several analytical approaches for the qualitative and quantitative LC-MS analysis of therapeutic proteins, such as monoclonal antibodies, bispecific antibodies and antibody-drug conjugates (ADC) in biological matrices. We have successfully applied LC-MS methods for method development of monoclonal and bispecific antibodies and ADCs in biological matrices, followed by validation of the method and analysis of study samples from (pre-)clinical studies, also under GLP.
The experimental set-up for LC-MS methods for therapeutic proteins in biological matrices depends on the type of analyte protein, the research question and the development phase of a therapeutic protein.