The purpose of the Analytical Core is to provide support to the various Projects for the structural and quantitative analysis of drugs and metabolites. The Core will provide sensitive and specific assay methodology based on chiral HPLC, GC/MS and LC/MS. Structural analyses will be carried out on one of the nine mass spectrometers that will be available in the Core. Confirmation of structures will involve the use of NMR spectroscopy and total synthesis of novel metabolites. In addition to using existing methods it is proposed to develop new methods for drug and metabolite analysis based on capillary HPLC in combination with electrospray mass spectrometry. It is anticipated that this will also provide a new powerful way to carry out quantitative analyses. We also propose to explore the use of a new four-sector tandem mass spectrometer for carrying out the structural elucidation of metabolites. This instrument will be fitted with a photodiode array detector and so will be extremely sensitive. Of particular interest will be the coupling of high resolution electrospray ionization with the high energy collision regime that is available on the four sector instrument. Samples will be introduced into the electrospray source using an ABI-based capillary HPLC system that was recently constructed in our laboratory. The Analytical Core will also provide a resource for the synthesis of drug enantiomers, their metabolites, and stable isotope standards for use in stable isotope dilution assays.
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