This new symposium series from PBSS will provide important value to life science industry scientists, since much of the R&D work of our industry nowadays is done at the vendors (CROs, CDMOs, tool makers etc). These scientific symposia will present unique technologies and valuable scientific case studies from vendor labs. 

Topics:

  • Recent trends and applications of hybrid LBA/LC-MS/MS technologies for ultra-sensitive quantification
  • Acceptance criteria for regulated bioanalysis of large molecules: navigating evolving standards
  • Bioanalysis of antibody-drug conjugates (ADCs): challenges in measuring both payload and antibody
  • Bioanalytical and ADME challenges in targeted protein degradation (e.g., PROTACs)
  • ADME profiling of emerging modalities including oligonucleotides, peptides, and antibody-drug conjugates
  • Implications of the ICH M12 guidance on drug-drug interactions

Presentation from KCAS Bio

LC-MS/MS Bioanalytical Strategies for Various Therapeutic Drugs and their Conjugates (ADCs, Oligos, siRNA, ASOs and AOCs/ARCs) by QqQ and HRMS.  Strategies and Case Studies by Dawn Dufield, PhD

Bioanalysis for support of next generation Antibody Drug Conjugates (ADCs) and Antibody siRNA Conjugates (ARCs) or Oligonucleotide therapeutics have exploded recently due to the efficacy and safety that these therapies offer for immuno-oncology, rare diseases, genetic disorders, vaccines and potentially many other diseases.

We have seen the role of hybrid LC-MS/MS in the analysis of antibody-drug conjugates (ADC/AOCs) increase 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, we have seen 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.

Lately, we have seen a trend towards all analyses being done by LC-MS/MS. Hybrid LC-MS/MS can easily be used to monitor both the total antibody as well as the ADC conjugate or the siRNA or ASO associated with an AOC.  Depending on the type of conjugation and linker used (site-specific vs Cys or Lys conjugation and cleavable vs non-cleavable,) and what reagents are available, hybrid LC-MS/MS offers several strategies or advantages to monitor the various constituent parts of the conjugate.

Bioanalysis is a continually evolving field. Hybrid LC-MS/MS or LC-MS/MS using QqQ or HRMS is proving to be an increasingly valuable tool for delivering answers about complex analytes such as antibody drug/oligo conjugates or oligos to enhance the drug development process. This presentation will highlight the bioanalytical strategy used in the analysis of various antibody drug conjugates/new modalities (payload, oligo, peptide, radionuclide, etc.) with several case studies.

About the Speaker

Dawn R. Dufield is the Scientific Officer for Mass Spectrometry at KCAS Bio. She has been at KCAS since 2018 and was previously with Pfizer for over 20 years working in the quantitative large and small molecule LC-MS/MS field. She was one of the early pioneers of using immunoaffinity combined with LC-MS/MS to offer additional selectivity which is now commonly referred to as Hybrid LCMS and is a co-author on a white paper on recommendations for validation of LCMS based bioanalytical methods for protein biotherapeutics. She has been working on the Bioanalysis of ADCs for over 15 years and the last several years on Oligos/ARCs. She has numerous publications in her field and is an active member of the WRIB, AAPS and ASMS.

Contact Us to Learn More and Start a Conversation

Are you attending PBSS? Don’t miss the chance to discuss your project’s needs with Dawn Dufield, PhD and Sara Hermann. Contact us to schedule a meeting and explore how our services can support your bioanalytical and drug development objectives.