Hybrid FTMS

The reason for the disparity between the MS/MS spectra from the two detectors originates from a time-of-flight effect, which is also observed in a full-scan MS mode and is a consequence of the spatial separation between the two mass detectors. The result is a discrimination against the lower mass region when scanning a relatively wide mass range (e.g., 85-850 Da) and is a feature on most hybrid FTMS... 

Figure 9.25 Exploded view of an ICR ion trap. The ICR has been the primary mass analyzer used in FTMS, both alone and in newer hybrid FTMS instruments.

Following the development of the hybrid Q-FTMS instruments, a linear ion trap (LIT) was used in place of the mass-filtering quadrupole and storage multipole. This hybrid-FTMS configuration is found in some commercial FTMS instruments, and an example of this instrument configuration is shown in Figure 11.20C. Ions pass from the ESI source into the LIT where they are stored, and then they are passed down to the analyzer cell. With the LIT, ion accumulation, mass selection, and dissociation (including MS") can be performed within the LIT instead of the analyzer cell. CAD is typically performed within the LIT, while other methods of ion activation, infrared multiphoton dissociation (IRMPD), and electron capture dissociation (ECD) (vide infra) are performed inside the analyzer cell. One unique... 

FTMS. Ion activation by collisions with neutral molecules, photoexcitation, and electron interactions have aU been applied to FTMS. The recent development of hybrid FTMS instmmentation allows MS/MS to be performed outside of the cell, thus improving the duty cycle. Discussion of MS/MS capabilities of FTMS will be divided into two sections, in-ceU (or internal) MS/MS and external MS/MS. 

Orbitrap The newest of the major mass analyzers, the Orbitrap is a hybrid MS consisting of a LIT mass analyzer, or transmission quadmpoles connected to the high-resolution Orbitrap mass analyzer. The Orbitrap utilizes electrical fields between sections of a roughly egg-shaped outer electrode and an inner (spindle) electrode (Chapter 5). Ions orbit between the inner and outer electrodes and their oscillation is recorded on detector plates (Hardman and Makarov, 2003 Hu et al., 2005). As with the FTICR, fast Fourier transform of the raw data is used to convert the data for mass analysis, making the Orbitrap the second major type of FTMS instrument. The resolving power of the Orbitrap is intermediate... 

Sanders, M., Shipkova, P. A., Zhang, H., and Warrack, B. M. (2006). Utility of the hybrid LTQ-FTMS for drug metabolism applications. Curr. Drug Metab. 7 547-555. 

Due to its radically different design, the latest hybrid linear ion trap FTMS instrument, the LTQ-Orbitrap (Fig. 5.6), does not suffer from the time-of-flight effect. In this instrument, the superconducting magnet and the ICR cell are replaced by an electrostatic trap (C-trap) and so distances traveled by the ions from one MS device to the other are much smaller in addition a radically different ion transfer mechanism virtually eliminates any possibility for a time-of-flight effect (Makarov,... 

Although both hybrid LTQ-FTMS instruments find applications in the dmg metabolism area, the LTQ-Qrbitrap, with its simplified maintenance, lower cost, and in most cases better sensitivity at low masses, is generally more applicable to small-molecule analysis. The LTQ-FTICR, with the advantage of higher resolution and mass accuracy, covers a wider range of applications, from small molecules to peptides and proteins, where most advantages are found in the analysis of large biomolecules. 

Josephs, J. L., Grubb, M. F., Shipkova, P., Langish, R., and Sanders, M. (2005). A comprehensive strategy for the characterization and optimization of metabolic profiles of compounds using a hybrid linear ion trap/FTMS. In Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX. 

An IT analyser has also been coupled to an ICR FTMS instrument, yielding a hybrid instrument in the IT ICR configuration. This hybrid instrument gives high sensitivity at the attomole level, a high resolution of 100000FWHM at 1 s scan rate and a high mass accuracy of 1 to 2 ppm with external calibration at 1 scan per second. A similar hybrid instrument in which the ICR analyser is replaced by an orbitrap analyser has also been... 

Gatto et al m characterized the mechanism of L-pipecolic acid formation by cyclodeaminase RapL from L-lysine within rapamycin biosynthesis, which is a hybrid NRP—polyketide antibiotic (Figure 25(a)). RapL was characterized by biochemical assays to require cofactor nicotinamide adenine dinucleotide (NAD+) and an oxidative cyclodeamination reaction mechanism corresponding to ornithine cyclodeamination was proposed based on ESI-FTMS analysis of RapL reaction products (Figure 25(b)). 

Q-TOF) and quadrupole FTMS (Q-FTMS), significantly increases the specificity and sensitivity of LC-MS and provides for the analysis of highly complex mixtures. This idea has existed in the FTMS community for some time and was recently achieved by the Smith [95] and Marshall Laboratories [96]. The Q-FTMS hybrid allows for greatly enhanced dynamic range via gas-phase selection and concentration of analyte in a quadrupole trap, with subsequent high-resolution MS and MS/MS analysis in FT electromagnetic trap. 

The recently introduced LTQ-Orbitrap is another hybrid detection instrument, where the superconducting magnet and the ICR cell in an FTICR instrument are replaced by an electrostatic trap providing performance close to that of an FTICR instrument [25,28], The LTQ-Orbitrap shows excellent performance for small molecule MS/MS. It can achieve high mass resolution up to 150,000 and mass accuracy (1 ppm) [19,29], In most cases, the sensitivity of Orbitrap detection is superior to the FTICR detection of small molecules. Low mass transmission does not appear to be an issue, as spectra are very similar to those from the LTQ. Mass accuracies did not appear to be as precise as those for the LTQ-FTMS however, with the vast majority of mass measurements falling within 3 ppm, its performance is well suited for structure elucidation. 

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