The drug discovery industry widely uses LC-MS as an analytical technique due to its inherent sensitivity and selectivity. This technique has revolutionised areas of the drug discovery process, in particular lead optimisation, where tandem quadrupole mass spectrometry is widely used to generate ADME information for new compounds.
With LC-MS/MS, quantitative data is usually provided by MRM experiments. One disadvantage of this approach is that no qualitative information is available from a single analytical MRM experiment. There is potential to overcome this by the use of LC to coupled orthogonal acceleration time of flight (oa-Tof) mass spectrometers, which can provide both sensitive and accurate qualitative and quantitative information from a single analysis. Previously, attempts to use LC-Tof instruments have been restricted by the limited dynamic range of these instruments, which lead to errors in quantification at high drug or metabolite concentrations.
Here we present data using an LC-Tof system with extended dynamic range capability that extends the utility of this technology for metabolism studies.
This poster was presented at ISSX Drug Metabolism in Vancouver, B.C., Aug 29-Sept. 1, 2004.