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Metabolite Identification
Identification of metabolites from both in vitro test and in vivo animal studies are often necessary in the discovery and pre-clinic development of a drug candidate. In vitro experiments, using animal or human hepatocytes and microsomes, can provide a rapid and cost-effective screening to identify potential toxic metabolites, but the results from in vitro experiments may not correlate with that from in vivo studies using whole animals, partially due to that the complicated drug uptake, transport, and interactions with biomolecules at cell or organ level are missing or over-simplified in a in vitro system. However, due to the low level of metabolites from in vivo samples, it is often difficult to identify metabolites from a in vivo experiment, and a high sensitive mass spectrometric technique become necessary to elucidate the structure of in vivo metabolites.

To overcome those difficulties, we have developed a ultra-sensitive procedure for characterizing metabolites from in vivo and in vitro experiments. Our Nano LC-MS/MS based MetID platform, equipped with a NanoHPLC with a 75 um capillary column, can potentially lead to a 3760 fold increase of MS detection sensitivity over a LC-MS system with a 4.6 mm column. The ion trap mass spectrometer used is the most sensitive type of mass spectrometers currently available, due to its ability to accumulate ions over a period of time. Its capacity to carry out MSn experiment provide a very powerful tool in elucidating the chemical structures of metabolites.

 

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