A hybrid LBA/LC-MS assay: realize the best of both worlds
Traditionally, the pharmacokinetic profile of biotherapeutics such as insulin glargine, adalimumab, trastuzumab and others, used gold standard LBAs to assess dose response during drug discovery and development; however, LBAs require a specific antibody reagent to be developed for each mAb variant, a process that is often not compatible with the compressed timeframes encountered during the initial stages of drug development. More recently, LC-MS/MS-based methods have come to the forefront as a feasible approach for the quantification of biotherapeutics in biological matrices, with many of these methods relying on proteolytic digestion of the target mAb and quantification of multiple unique signature peptides, which are equivalent to levels of the whole protein. But, in order to drive the real biological need, we have to quantify the pharmacologically active or free form of the drug to assess safety, efficacy and proper dosing regimen. Here we present a solution to get the best of both technologies: an LBA strategy to capture the active form of the drug; and an LC-MS assay to selectively quantify the free and circulating drug.
What will you learn?
- Immunocapture sample extraction strategies
- How to improve selectivity and specificity of biotherapeutics quantitation
- Hybrid LBA/LC-MS/MS assay step-by-step method development process
- Comprehensive workflow development for insulin glargine quantitation in human plasma
Who may this interest?
- Small molecule (LC-MS) bioanalytical scientists with an interest in large molecule quantitation
- Bioanalytical scientists with a background in LBAs and an interest in mass spectrometry
Speakers
Suma Ramagiri, PhD
Global Application Manager (Pharma/BioPharma/CRO Business Unit)
SCIEX
Suma Ramagiri received a BSc in Biochemistry and an MSc in Organic Chemistry in India. She did her PhD in Analytical Chemistry and post-doctoral research at the University of Tennessee Health Sciences, Memphis (TN, USA). Suma obtained Business Management from Ryerson University (Toronto, Canada). Suma brings more than 12 years of experience in the analytical instrumentation field through working at Dr Reddy’s Laboratories (Hyderabad, India) and GTx, Inc. and ED Labs in Memphis (TN, USA). She has worked in many drug discovery and development projects for antibacterial, anti-inflammatory and anticancer drugs, DMPK studies and GLP bioanalysis. In her current role as a Global Application Manager, Pharmaceutical & CRO business at SCIEX, Suma leads innovative analytical and bioanalytical workflows in both traditional small molecule and also various biologic compound classes such as peptides, proteins, oligonucleotides, monoclonal antibodies and antibody–drug conjugates, a growing segment within pharmaceuticals and biopharmaceuticals. She drives worldwide efforts in application development and analytical product development to enhance bioanalytical quantitation, drug metabolism, biomarker quantitation, metabolomics and impurity analysis. Suma has over 15 publications in scientific journals and has presented at conferences and tradeshows worldwide.
Lei Xiong, PhD
Application Scientist, Advance Workflow and Method Factory
SCIEX
Lei Xiong received her BSc in Chemistry from the University of Science and Technology of China (Anhui, China). In January 2011, she received her PhD in Analytical Chemistry from Yingsheng Wang’s group at the University of California Riverside (CA, USA), where she focused on mass spectrometric application of quantitative proteomics of biomarker discovery for anticancer drug treatment and characterization of protein post-translational modification. After graduation, she joined Shimadzu as an LC-MS Demonstration Scientist. In December 2011, she joined SCIEX as an Application Scientist to support method development, instrument demonstration, customer training and field application support. Her current role as the Technical Leader of Advance Workflow and Method Development, specifically focuses on biopharmaceutical, peptide quantitation and proteomics application areas. Lei has published over 15 papers in global leading scientific journals and has presented in conferences and events worldwide.
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