*JANUSZ PAWLISZYN

In-vivo Solid Phase Microextraction Integrated with Mass Spectrometry Platform for Untargeted and Targeted Investigation of the Brain

Challenge: One of the major challenges currently faced by the pharmaceutical industry is the development of alternative approaches that allow the gathering of maximum information using a minimum number of animals. With regard to analytical instruments, mass spectrometers offer increasingly sensitive and quantitative determination of biological molecules. However, collected biological samples, especially tissues, require efficient sample preparation prior to mass spectrum (MS) analysis, which is a bottleneck in a typical workflow.

Solution: This project integrates the non-lethal, low-invasive in vivo sampling Solid Phase Microextraction (SPME) chemical biopsy approach with MS detection to 1) obtain a correct profile of the brain metabolome and lipidome; 2) quantify drugs and monitor of their metabolism, and 3) obtain high resolution chemical imaging of deep brain structures. This integrated analytical platform results in sparing of animals because no biospecimen (tissue or fluid) withdrawal is required, just metabolites are extracted. Therefore, the same animal can be used repeatably. This in turn will reduce the overall cost of analysis and should allow for development of standardized drug discovery protocols and sample preparation methods while avoiding the use of large animal cohorts.

Achievements/Impact: The integrated analytical platform developed in this project increases the quality of in vivo data in the drug discovery process by allowing the collection of more information about the effect of different brain stimuli. The non-lethal nature of the sampling and easy-to-operate brain sampler will significantly reduce the number of animals used, eliminate statistical inter-individual variability, and allows for the observation of long-term effects of drugs in the same animal. This approach will also lead to more optimum use of drugs in personalized medicine. In vivo SPME enables more efficient drug development by reducing required R&D resources and ultimately shortening the time to market approval.

Principal Investigator:

Janusz Pawliszyn
University of Waterloo

Co-investigators

Dajana Vuckovic
Concordia University

Clement Hamani
Centre for Addiction and Mental Health (CAMH)

Completed Project
$996,000 $ / 3 years
Supported by CQDM through:
• Merck
• Pfizer
• MESI
And by co-funding partners:
• Brain Canada
• Ontario Brain Institute