Utility of the Hybrid LTQ-FTMS for Drug Metabolism Applications

Fourier Transform Ion Cyclotron Mass Spectrometry (FTMS) provides the highest mass accuracy and mass re-solving power of the currently available mass spectrometers. One of the main drawbacks in its use for absorption, distri-bution, metabolism and excretion (ADME) applications has been its incompatibility with standard HPLC columns andflow rates. Hybrid instruments, such as the LTQ-FT, provide the much needed bridge between the excellent performanceand capabilities of the FT mass spectrometers and the well-established, tested and validated features of quadrupoles andion traps. The hybrid instruments are compatible with standard HPLC flow rates, have high-throughput and automationcompatibility, and also provide data dependant MSn. The ability to maintain the fidelity of an externally calibrated accu-rate mass measurement across an HPLC peak, where the analyte concentrations are rapidly changing, is a significant ad-vance for this technology, as is the ability to perform data dependent MS/MS experiments on the chromatographic timescale. The MSn and accurate mass capabilities are routinely utilized to rapidly confirm the identification of expected me-tabolites or to elucidate the structures of unusual or unexpected metabolites. The combination of traditional high-flowchromatography and robust, externally calibrated accurate mass determination for both parent and product ions makes theLTQ-FTMS a very powerful analytical tool for the characterization of metabolites, identification of metabolic soft-spotsand for metabonomics studies.