An author’s perspective: Rachel Foreman on optimized LC-MS/MS methods for quantifying ADC payloads

Written by Rachel Foreman (AstraZeneca)
An author's perspective Drug development MS (LC–MS/MS, HRMS, IMS)

Author: Rachel Foreman, Senior Scientist, Drug Discovery Bioanalysis Group, AstraZeneca (Cambridge, UK)

Rachel is a Senior Scientist in the Discovery Bioanalysis Group at AstraZeneca, specializing in targeted LC-MS/MS assays for early drug compounds and biomarker measurement. She works in collaboration with numerous teams to support the growing in vitro platform for safety assessments of novel oncology treatments. Before this role, Rachel completed her PhD in Clinical Biochemistry at the University of Cambridge (UK), where she developed bioanalytical methods to identify and quantitate novel peptide biomarkers for metabolism. It was during this research that Rachel learnt the importance of optimizing methods to improve assay detection limits and the potential benefits of using in vitro models for understanding diseases and therapeutic treatment.

  1. Please could you provide a brief summary of your paper

Our paper describes the development of a suitable extraction method for the free drug component of an antibody drug conjugate, in samples from an in vitro 3D bone marrow model. There are specific additives in cell media that are vital for monitoring culture conditions, however these can be detrimental to bioanalytical systems such as liquid chromatography mass spectrometry. We therefore undertook an extensive investigation into three different extraction techniques to determine which was best at removing matrix interferences without affecting the target analyte.

READ THE FULL PAPER HERE

  1. What is most inspiring to you about a career in bioanalysis? What sparked your interest in supporting in vitro sample analysis?

It still amazes me that using bioanalytical techniques like mass spectrometry we can glean so much information from complex biological samples! In my role I support a wide range of projects, from understanding therapeutic pharmacokinetics to identifying novel disease biomarkers. The data we can generate is essential for drug development and understanding biological systems, and the advancement of in vitro models means we can take an even more detailed look at drug interactions at a cellular level.

  1. What are some of the challenges you came across during this study? How do the results of your paper help to overcome challenges in using in vitro models for drug development?

As described in the paper, a number of different methods were investigated, and it took some time to find the optimal conditions for each technique. With all bioanalytical methods there needs to be a balance between removing as much matrix interference as possible while still recovering the target analyte, which can require some trial and error to find the best combination. In addition, specific drug compounds may have different physiochemical properties and therefore interact differently during the extraction process.

But in this instance, by applying ion exchange solid phase extraction, a suitable method was found for removing cell media additives without affecting drug recovery and this assay continues to be applied to other target analytes with great success. This has allowed my team to confidently support multiple in vitro studies with hundreds of samples, without any detrimental effects to our bioanalytical systems.

  1. How would you most like to see this research used in the bioanalytical field?

I believe biologically relevant in vitro models are essential for understanding complex drug cellular interactions, and I think it’s great that we’ve been able to optimize our extraction methods to be able to support these studies. I hope that our method is useful to other bioanalytical scientists who are faced with similar analytical requests, as pharmaceutical research moves towards in vitro models as an alternative to preclinical animal models.

  1. What are you hoping to achieve next in this research area?

I will be continuing to support in vitro studies for drug development and safety, and my next aims include quantifying the biodistribution and dynamics of the target drugs in these complex microphysiological systems. Our methods will need to be continuously improved to keep up with the development of both the in vitro model and new drug compounds.

  1. What advice would you give someone who is interested in working in this field?

Bioanalysis is a really broad and interesting field, but I think it’s important to understand the basics early on, before jumping into the complicated assays! There are plenty of training platforms available now to learn the fundamentals, and I think these are invaluable when starting a career in bioanalytical method development.  After a while you’ll see that it’s a really rewarding area of science to work in, as you’ll be able to see your data and methods contribute to the progress of developing life-changing medicines.

Disclaimer: the opinions expressed are solely those of the author and do not express the views or opinions of Bioanalysis Zone or Taylor & Francis Group.