Metabonomics MS coupled to HPLC shows potential for the screening of rat urine in drug development

Library Number:
720000544EN
Part Number:
720000544EN
Author(s):
Stumpf, C;Castro-Perez, J;Haselden, J;Plumb, R;Sweatman, B;Conner, S
Source:
50th ASMS Conference; Orlando; 2nd-6th June; 2003
Content Type:
Posters
Content Subtype:
ASMS
Metabonomics is a rapidly growing area of scientific research. It is a systems approach for studying in vivo metabolic profiles and can provide information on disease state, toxicity and gene function. In metabonomics the effect of a pharmaceutical candidate on a whole animal or organism is investigated by measuring the changes in endogenous metabolites over a time course following compound adminstration. The analytical data generated in these studies is analyzed by mathematical techniques such as principal component analysis (PCA) to highlight both subtle and gross differences in the samples. This metabonomics approach is now being investigated by large pharmaceutical companies to screen compounds for toxicity, lead compound selection and human disease profiles to name a few. To date the vast majority of work in this field has utilized 1H-NMR as the analytical method of choice. While being very effective, NMR has two significant disadvantages: poor sensitivity and lack of analyte resolution leading to the masking of low abundance analytes by high concentration components. Electrospray LC/MS has become the technique of choice for bioanalysis, both quantitative and qualitative. Here we describe how electrospray LC/MS can be successfully employed in the metabonomic analysis of rat urine derived from a toxicological study.

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