Research
Research focus and main objectives
The research activities of the Laboratory of Medical Biochemistry and Clinical Analysis can be divided in two main parts: bioanalysis and pharmacokinetic & pharmacodynamic (PKPD) modelling.
In terms of bioanalysis, our activities mainly focus on the (quantitative) analysis of various endogenous and xenobiotic (drug) substances in biological matrices such as serum, urine and (tumor) tissue. These assays are developed in support of preclinical and clinical studies and are primarily focused on liquid chromatography-mass spectrometry [LC-MS] and to some extent also on gas chromatography-mass spectrometry [GC-MS]. Furthermore, as it represents a pivotal component of assay development, a substantial part of our work is devoted to the study of sample clean-up approaches. The compounds under investigation range from small molecules, such as metabolites, substances of abuse and lead drug molecules, to bio-polymers such as peptides and proteins.
At the moment, our bioanalytical R&D focusses on three domains. The first domain relates to the analysis of tumor tissue to obtain spatial penetration data of chemotherapeutics (taxanes, platinum-related compounds, etc.). Secondly, we focus on the quantitative determination of (unbound) antibiotics in serum and urine samples from ICU patients, pediatrics, etc. Finally, assays are being developed to quantify probe substrates that are used in in-vitro screens in support of bottom-up PBPK modelling.
The second part of our research activities are focused on different aspects of PK(PD) modelling. As such, different population PKPD as well as Physiologically-Based PK (PBPK) modelling projects are ongoing, spanning the entire drug development arena, and ranging from in-vitro to pre-clinical to finally clinical. The main research topics of these projects are: (i) the use of PBPK and bottom-up in-vitro in-vivo extrapolation approaches to expedite drug development in specific patient populations (e.g. pediatrics), (ii) PKPD – biomarker models as tools to individualize/optimize chemotherapy treatment (e.g. intraperitoneal delivery of paclitaxel) and (iii) Population PKPD modelling to allow treatment individualization in the clinic (e.g. antibacterial therapy in critically ill or morbidly obese patients).