Application of MALDI Mass SpectrometrY Imaging (MSI) to Drug Development
MALDI MS Imaging is a powerful technique that is especially useful for researchers in the pharmaceutical field. Researchers can visualize the effects of new therapies by determining the precise distribution of drugs and drug metabolites in a tissue section. Researchers can also extend their understanding of therapeutic pathways by comparing the proteomic make up of healthy and diseased organisms.
Imaging of Drug Metabolism without Radioactive Isotope Labeling
The ability to detect molecules with mass ranges up to 500,000 Daltons makes mass spectrometry a favored detection technique for drug research. In addition, the precise characterization of bio-markers, without the need for radio isotope labeling or tagging, simplifies processes and enables de novo identification.
“Top-Down” analysis: Direct measure of the mass (m/z) of intact, small or large, bio-molecules and possible analysis of molecule fragments for additional structure information.
“Bottom-Up” analysis: Direct measure of the mass (m/z) of fragmented bio-molecules and analysis of these fragment molecules by LC/MS or MALDI/MS to identify the original molecule. A typical application is the digestion of proteins into peptides (e.g.: trypsin digestion) and the de novo sequencing of the original protein based on the identification of its sub-components.
Mapping Large Quantities of Data into Easy to Interpret Images
By relating the analytical MALDI MS data to the X-Y coordinates of the MALDI laser at the time of analysis, MALDI MS Imaging provides researchers the ability to determine the exact distribution pattern of drugs and drug metabolites throughout a tissue section or an entire study animal section. The MS data is easily exported into an imaging software package, such as NOVARTIS’ BioMap (Free download at www.msi-imaging.com), for image generation and presentation.
Understanding Biological Pathways and Visualizing the Effect of Potential Treatments
Understanding the distribution of specific proteins in a tissue, as well as other molecules such as lipids and metabolites, can be of great help to understand complex diseases, such as Alzheimer’s. The “Molecular Images” generated by MALDI MS can be used as molecular signature for pathological progression, and therefore, be also used to evaluate the benefits of new therapies.
Applications of MALDI MS Imaging in Drug Development
Make earlier go/no-go decisions based on drug distribution.
Optimize drug delivery mechanism (E.g.: Application to dermatology by observing the penetration pattern of drugs in epidermal tissue. Selection of optimum carriers).
Identify compounds faster by obtaining accurate mass information directly from tissue samples.
Determine precise compound distribution by acquiring high-spatial resolution images.
Method Development Resources
HTX Imaging provides full method development services to help labs optimize sample preparation prior to MS Imaging. Optimized sample preparation helps increase analytes extraction and signal intensity for improved Mass Spec data. The unique ability to control spray temperature is key in accelerating extraction while reducing delocalisation.
In the example below, scientists at Sheffield-Hallam University and GSK optimized flow rate and stage velocity for improved extraction of a new drug candidate. Spray nozzle temperature of 80 Deg C allows very fast sample preparation and flow rates 5 to 10 times higher than other available matrix sprayers.