We are requesting funds to upgrade our mass spectrometry capabilities. Until this year, Dr Nagar's and Korzekwa's laboratories have used two standard resolution mass spectrometers (Sciex API 4000s) for all LCMSMS quantitation. Although these instruments are excellent for routine quantitation of drugs and metabolites from in vitro and plasma samples, they are not high-resolution instruments and are not ideal for protein quantitation. Unexpectedly, we have recently acquired a Bruker Solarix 7T FT-ICR mass spectrometer (< two years old). This instrument has a 7-tesla magnet and is an ultra-high-resolution instrument capable of measuring molecular masses with 1 in 2.5 million resolution. This instrument is equipped with both MALDI and API interfaces, which allows identification and quantification of both small molecules and proteins. In addition to exact-mass analysis and quantitation of drugs and metabolites from in vitro and plasma samples, this instrument can perform mass spectrometry imaging, the spatial quantitation of drugs and metabolites directly from tissues 1,2. We are requesting two upgrades for the Bruker Solarix 7T FT-ICR mass spectrometer. First, we are requesting funds to purchase an HTX M5 Sprayer MALDI matrix deposition system and second, an Agilent 1290 high performance HPLC. These upgrades will be used for sample preparation and introduction into the FT-ICR mass spectrometer through the MALDI imaging and API interfaces, respectively. The requested upgrade to this instrument will allow us to greatly expand our analytical capabilities and generate unanticipated datasets that will help achieve our Specific Aims outlined in the abstract above for NIH grant 2R01GM104178 `Predicting intracellular concentrations in the presence of transporters'.
We are requesting funds to upgrade a high-resolution mass spectrometer capable of tissue imaging as part of our NIH grant 2R01GM104178 `Predicting intracellular concentrations in the presence of transporters'. The overall goal of this research is to better predict drug efficacy and safety in humans. Biophysical methods, in vitro, in situ, and in vivo data will be used to develop models that incorporate membrane partitioning, permeability-limited diffusion, blood flow, active transport, and metabolism in order to predict intracellular and extracellular drug concentration- time profiles.
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