The Investigation of Biomarkers of Nephrotoxicity Using a Metabonomic UPLC/MS Approach

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Hilary Major (Waters) and Ian Wilson (Department of Drug Metabolism and Pharmacokinetics, AstraZeneca)
Genomes to System Conference, Manchester UK, March 24-26 2006
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Other Symposium
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UPLC/TOF MS in conjunction with principal components analysis has been shown to be a valuable tool in the study of renal toxins.The changes to the endogenous urinary metabolite concentrations have been used to track the onset of nephrotoxicity over time.The enhanced chromatographic resolution and increased sensitivity of UPLC coupled with the fast acquisition rates and sensitivity of the TOF mass spectrometer allowed the detection of low level metabolites.Exact mass measurements have been used to facilitate database searching for identification of the potential biomarkers, although their biological significance still needs to be determined. UPLC/TOF MS based metabonomics has the potential to be an integral part of toxicological screening and lead compound selection in the pharmaceutical industry and should help to minimise late stage attrition of candidate drugs.

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