Utility of the hybrid LTQ-FTMS for drug metabolism applications.

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