Mass spectrometry imaging in drug discovery
Mass spectrometry imaging allows direct measurement of the molecular composition of a sample. It can be used to image the spatial distribution of exogenous drugs and endogenous metabolites simultaneously over the surface of tissue sections or small biopsy, allowing new insights into both compound efficacy and safety during drug discovery.
This label-free imaging modality is influencing pharmaceutical research primarily in pre-clinical discovery and development. However, mass spectrometry imaging is on the cusp of aiding translational research into clinical medicine to enhance patient stratification.
Tackling compound attrition is crucial in reducing the risk of significant financial losses or delay in bringing new medicines to market. It is of paramount importance during drug discovery to understand the efficacy and safety profile of a new therapeutic as soon as possible to allow effective project intervention, redesign of studies, or even cancellation. Efficacy and safety data can allow the findings from failures to positively impact future programmes.
Crucial to making timely project decisions is improved PKPD modelling, which can use translatable efficacy and safety biomarkers to connect the predicted patient population to preclinical animal models. Typically, this is based on quantitative plasma measurements of biomarkers and free-drug levels. These are assumed to be equivalent to tissue concentration. However, there is a significant risk that such assumptions are not always correct. Furthermore, there are many situations where we can assume there will be a discrepancy between plasma and tissue levels. Such situations include poorly vascularised tissues, following localised delivery (inhalation or targeted drug delivery) or the blood-brain barrier. In such cases, using established bioanalytical techniques such as…