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PhD defence P. (Peter) Bults

When:Mo 11-04-2022 14:30 - 15:30
Where:Academy Building

Pharmacokinetics and biotransformation of biopharmaceuticals

Unlike the current situation for small-molecule drugs, the biotransformation of biopharmaceuticals is a largely unexplored field. Although much attention is paid to (the prevention of) degradation and structural alteration of protein-based drugs in pharmaceutical formulations, almost nothing is known about what happens to such a drug once it is dosed to a patient. An important reason for this is the fact that it is virtually impossible to investigate biotransformation using LBAs, because they typically cannot distinguish unchanged and biotransformed versions of the drug. With the increasing use of LC-MS/MS for protein quantification, it is now becoming more and more evident that in vivo chemical and enzymatic reactions of biopharmaceuticals are very common. Pharmacologically, biotransformation may affect the activity of a protein drug and, from an analytical perspective, it can also have a large influence on the concentration result that is reported.If we look at biopharmaceutical analysis from a more technical and instrumental point of view. So far, most protein LC-MS methods are being performed using triple-quadrupole mass spectrometry after sample digestion and further sample processing. This type of mass spectrometry has unit-mass resolution and its use for protein quantification essentially is an extension of the typical approach for small-molecule analysis. Very little is known about the quantitative possibilities of other high-resolution mass spectrometry (HRMS) approaches for biopharmaceuticals. HRMS is extensively used for qualitative purposes, such as the structural elucidation or confirmation of both small and large molecules, because of its high mass accuracy, but it also offers the option for quantitative analysis and extensive data re-processing. It can thus be used as an alternative detection technique for digested protein analysis with improved selectivity compared to unit-mass MS and it also is capable of quantifying intact proteins, which is virtually impossible on triple-quadrupole instrumentation.

Promotores Prof.dr. N.C. van der Merbel and Prof.dr. R.P.H. Bischoff

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