IMAGING MASS SPECTROMETRY BASED APPROACHES TO THE LOCALISATION OF DRUGS AND DRUG METABOLITES IN ANIMAL TISSUE

摘要

Combining IMS separation with MS/MS fragmentation greatly improves the selectivity of both MALDI-MS and LESA-MS experiments. Using the selective approach developed for LESA-MS, diclofenac has been successfully identified in dosed mice whole-body tissue sections, showing data complementary to existing QWBA studies. The method developed for MALDI-MS improves the selectivity of the experiment by an order of magnitude allowing diclofenac to be confidently identified at 100 ng on tissue, which equates to approx600 pg per pixel. A higher concentration of diclofenac needs to be present in dosed tissue sections for MALDI imaging experiments, but the enhanced selectivity demonstrated here means this dose will still be within toxicity limits for the animal. The larger sampling area of the LESA technique provides an inherent advantage over MALDI in detection of lower concentrations of compound in complex tissue sections, but provides a much lower spatial resolution. Further optimisation will be required to determine the most selective method for detection of metabolites in tissue for both LESA-MS and MALDI-MS. Experiments to distinguish between diclofenac and its metabolites in dosed tissue will be investigated and compared with existing QWBA data.