Imaging Mass Spectrometry Approaches to Drug Localisation in Tissue
The aim of my PhD project is to evaluate different imaging mass spectrometry approaches for the localisation of drug compounds and drug metabolites in animal tissue.
- MALDI Imaging: MALDI Synapt G2 HDMS (Waters Corporation, Manchester, UK)
- Liquid Extraction Surface Analysis: TriVersa NanoMate (Advion BioSciences, Inc, Ithaca, NY, USA) coupled to a Synapt G2 HDMS.
Imaging Mass Spectrometry
A crucial and challenging aspect of the drug development process is being able to measure the distribution of a pharmaceutical compound and its metabolites in tissue. Quantitative whole-body autoradiography (QWBA) using 14C labelled drug compounds is the industry gold-standard for providing localisation information, but has some major limitations. QWBA cannot distinguish between parent drug and metabolites, as it is the radiolabel that is followed and not the drug itself1.
Mass spectrometry imaging (MSI) is an emerging technique that can distinguish spatially between the drug of interest and its metabolites. A number of MSI approaches have been described for localisation of drug compounds in tissue, most notably matrix-assisted laser desorption/ionisation (MALDI) imaging, pioneered by Caprioli et al. in 19972. These approaches provide data complementary to existing imaging techniques. A major challenge associated with MALDI imaging is the selectivity of the experiment for the compound of interest, due to the complex nature of tissue sections.
- Stoeckli, M., D. Staab, et al. (2007). "Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections." International Journal of Mass Spectrometry 260(2-3): 195-202.
- Caprioli, R. M., T. B. Farmer, et al. (1997). "Molecular imaging of biological samples: Localization of peptides and proteins using MALDI-TOF MS." Analytical Chemistry 69(23): 4751-4760.