CPSA Digest 2003

Day 2

Vendor Session - Drug Discovery Technologies & Applications

A Novel MS Based Metabonomic Approach to the Determination of Bio-markers of Drug Toxicity

Metabonomics is a rapidly growing area of scientific research primarily utilising proton NMR spectroscopy as the analytical method of choice. It involves the study of time-related metabolic profile changes that can be the result of exposure to a toxin or drug, to environmental effects or the onset of disease. The primary goal is to identify and quantitate small molecules in a biological system that are affected as the direct result of an external stimulus. Knowledge of these compounds, or biomarkers, can then be used for diagnosis, screening, or to direct further research. The metabonomics approach is now being widely investigated by large pharmaceutical companies in the area of drug discovery and development where an early indication of toxicity is of paramount importance in preventing the late attrition of a potential drug candidate. Hydrazine is a commonly used model hepatotoxin in animal studies and here we will present data from the analysis of rat urine samples from a toxicological study. Due to the wealth of data generated multivariate statistical analysis and pattern recognition methods were employed to classify the samples. We will show that this technique is a viable alternative to NMR spectroscopy for toxicology studies in drug discovery and development.

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