Native Mass Spectrometry Accelerates Biopharmaceutical Drug Development

It wasn’t so long ago that native mass spectrometry was seen as a thing of wizardry, firmly confined to the research domain. I have so much respect for the pioneers and innovators in this area; their persistent hard work, skill and dedicated belief in the value of this approach to provide genuine biological insights has ensured the accessibility of the technique for us mere mortals!

Native mass spectrometry (Native MS) enables the study of intact protein, non-covalent protein-protein and protein-ligand complexes in their biological state. Technically native MS is a process in which large biomolecules and their complexes are transferred from a 3D, functional existence in a condensed liquid phase to the gas phase via the process of electrospray ionization.

Data generated via native MS provides insights which are as close to the real biological state as possible, with minimal sample manipulation. It provides the ability to probe and understand the molecules structure and dynamics. What’s more, native MS provides important analytical benefits. With native MS proteins acquire fewer charges and yield spectra at a higher m/z thus reducing spectral interference. This is particularly important for very heterogeneous and complexed samples such as advanced biologics.

Here’s where native MS comes in as the tool of choice for accelerating biopharmaceutical drug development. At Symphogen, a clinical-stage antibody oncology-focused company, pioneering the application of complex mAb mixtures for cancer therapy, they are currently addressing throughput in monoclonal antibody lead selection studies using native MS.

At Symphogen native MS analysis has quickly become the method of choice and a workhorse platform for intact MS analysis for drug development, a transition that was driven by the versatility, gentleness, robustness and superior spectral data quality obtained by native MS on their Orbitrap platform.

A native SEC-MS method has become the preferred identity test, as it, in addition to advantages mentioned above, offers significant time saving when hundreds of samples need to be analysed. After extensive use of native SEC-MS, Symphogen have found that instrument performance is robust and stable over the course of a typical lead selection package involving approximately 400 samples analysed consecutively!

Symphogen have made the most of the native MS workflows within Chromeleon CDS, which provides then with a compliant environment for native MS analysis which is essential for their plans to transition this approach into more routine environments.

Chromeleon CDS can be used for data acquisition to data processing, assuring data integrity needs for MS methods implemented in the QC laboratory:

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