CRO Perspectives on the Use of HRMS in Regulated Bioanalysis

Triple quadrupole mass spectrometers have been the mainstay in regulated bioanalysis for the quantitation of therapeutic drugs due to their selectivity, sensitivity, and robustness. The MS/MS experiment, whereby parent m/z (Q1) and fragment m/z (Q3) of a molecule, offers valuable selectivity complementary to the LC separation. Recently, high resolution mass spectrometry (HRMS) instruments have added further refinement of mass resolution and accurate mass to the LC-MS and LC-MS/MS arsenal of the modern bioanalyst. HRMS is widely utilized in discovery settings for metabolite identification and elucidation of post-translational modifications (PTMs). However, its use in regulated bioanalysis is still evolving. With this session we want to promote discussions on the application of HRMS in comparison to, and as a complement to, QqQ instruments for regulated bioanalysis.
The first two speakers will be providing CRO perspectives on the use of HRMS in regulated bioanalysis. Steve Lowes, from Q2 Solutions, will speak on why and how to convert LC-QqQ and LBA bioanalytical methods to LC-HRMS as well as the pros and cons of using HRMS in regulated bioanalysis. The second speaker, Eric Thomas from LabCorp, will be discussing the role(s) of HRMS in the modern bioanalytical toolbox. The third speaker, John Kadavil from Food and Drug Administration (FDA), will elaborate on the current regulatory guidelines for using HRMS in bioanalytical studies, including best practices for assay development and method validation. This speaker will also delve into the challenges encountered when using HRMS in regulated bioanalysis, along with insights into emerging trends and future directions. The fourth speaker, Keyang Xu from Genentech, will provide the views from a pharmaceutical company’s perspective and will speak on the role of HRMS in ADC drug development for stability and biotransformation studies. A panel discussion of the opportunities and challenges of using HRMS instruments for regulated bioanalysis will conclude the session.

The use of triple quadrupole (QqQ) mass spectrometers has dominated the field of chromatographic regulated bioanalysis for over three decades. Through multiple case studies and practical requirements, HRMS is increasingly demonstrating utility in terms of selectivity and versatility that can supersede QqQ instruments.

This session is being proposed by the bioanalytical chromatographic focus group as there has been interest shown around the use of HRMS in regulated bioanalysis. We will promote this session in the AAPS bioanalytical community page prior to the conference to engage the audience and collect topics that might be of interest for discussion. During this session, the invited speakers will share their experiences, knowledge, and perspectives in the use of HRMS in regulated bioanalysis, a field that should resonate with the attendees. At the end of the presentations, the attendees will have the opportunity to interact with the presenters with questions/discussion. This session is targeted to bioanalytical scientists in CROs, pharmaceutical industry, and regulatory agencies in either regulated or non-regulated environments that are interested in learning more about the use of HRMS in bioanalysis as well as its applications in a regulated laboratory.