An evaluation of HRMS techniques on a Q-orbitrap vs. conventional SRM on a QQQ instrument for bioanalysis of biotherapeutic mAbs using the “universal” framework peptide assay approach for non-clinical species
Newer generation HRMS instruments offer advantages and different approaches for detection and quantification of biotherapeutics over today’s standard SRM approach using conventional triple quadrupole systems.
Biotherapeutics are increasingly prominent in the pharmaceutical industry, with monoclonal antibodies (mAbs) currently the largest approved class. Many new mAbs and multi-domain variants, such as bispecifics and antibody-drug conjugates (ADCs) are in development. While bioanalysis of “biologics” has traditionally used ligand-binding assay (LBA) technology, alternative or complimentary LC–MS-based methods have emerged. A popular example is the “universal” generic assay for mAbs being tested in non-clinical species. This presentation will compare results obtained for a sample set prepared using this approach and analyzed by HRMS on a Thermo Q-Exactiv and SRM on a conventional QQQ instrument and discuss future implications.
What will you learn?
- An understanding of the “universal” IA-LC–MS approach for mAb bioanalysis in non-clinical species and considerations for extending to techniques to human clinical applications
- Comparison of accuracy and precision, sensitivity, signal-to-noise, linearity, and selectivity/specificity for a sample batch analyzed by HRMS vs. low resolution SRM
- Differences and considerations in choosing the type of MS detection for bioanalysis of protein biotherapeutics
Who may this interest?
- CROs, Pharma and Biotech companies interested in utilizing LC–HRMS for quantitative bioanalysis of large molecules
- Mass spectrometrists and bioanalytical scientists
- Academicians and students interested in LC–MS bioanalysis
Diego F. Cortes is an R&D Manager with the chromatographic sciences department of PPD® Laboratories’ bioanalytical lab in Richmond,
Virginia, USA. Dr. Cortes earned a bachelor’s degree in biology from the Universidad del Valle, Cali, Colombia in 1999 and a Ph.D. in genetics, bioinformatics and computational biology from Virginia Polytechnic Institute and State University, Blacksburg, Virginia, in 2008. He has over 12 years of experience of scientific research in biological sciences, expanding from genomics and bioinformatics, to metabolomics, proteomics, and bioanalysis. He currently manages an R&D team in conducting bioanalytical method research and development primarily for biotherapeutics using LC-MS technologies.