Resolution orbitrap

Figure 2.7 Mass spectra recorded at different resolutions. Mass spectrum obtained by a two dimensional ion trap at low resolution (a) and by an Orbitrap at resolving power 50000 (b). Mass spectrum of a mixture of three isobaric species [C19H7N]+, [C20H9]+, [C13H19N302]+ obtained at low resolution (black line) and at resolving power 50000 (grey line) (c). It is noteworthy that at low resolution the three peaks are completely unresolved...

The Orbitrap allows very high resolution to be achieved (the resolving power in commercial instruments is 100000, rivalling that of FT-ICR instruments) and routine mass measurement accuracies less than 2 ppm. It finds applications in many fields, such as biology, proteomics, food chemistry and cultural heritage. 

MS11 capabilities. However, ions may then subsequently be detected at unit resolution using an electron multiplier or, alternatively, focused in a C-Trap (Figure 5.2) and then transferred and detected at high resolution using the Orbitrap. In our experience with the LTQ-Orbitrap, ions may be measured with a resolution of approximately 60,000 with online LC/MS in the full scan mode. 

One recent advance in MS hardware that has been found to be useful for metabolite identification studies is the Orbitrap. This MS has a mass resolution of 30,000 to 100,000 (two models). For many applications, 30,000 mass resolution capability is sufficient. While only a few current literature references cite the Orbitrap MS for metabolite identification, it is safe to predict that the Orbitrap will be the subject of many references in the future. Two references related to its use for metabolite identification are Peterman et al.190 and Lim et al.182 Lim s group related an an impressive example of the use of high mass resolution to differentiate a metabolite from a co-eluting isobaric matrix component, as shown in Figure 7.14. 

The orbitrap is the most recently invented mass analyzer. Like with the QIT, ions are trapped and stored in a potential well. However, instead of ejecting the ions for external detection the frequency of the trapped oscillationg ions is measured. This method provides substantially better resolution and mass accuracy in normal operation. 

The acquisition speed is, as for the FTICR, resolution dependent. With Thermo Fischer Scientific s orbitrap the desired mass resolving power can be selected. With the lowest setting (7500 FWHM) the acquisition time for one ion injection is 0.3 s and with the highest setting (100,000 FWHM) it is 1.9 s. 

The modem sector instruments have resolving power about 60,000 to 80,000, and in some cases up to 150,000. There are reports of resolution about 70,000 in the case of ion traps. The newly developed (2005) Orbitrap instruments demonstrated resolving power up to 200,000. Super high resolution (dozens of millions) may be achieved using FTMS (FTICR). 

With time of flight instruments, a mass accuracy better than 5 ppm can be achieved, while with Fourier transform ion cyclotron resonance or orbitrap mass spectrometers mass accuracies better than 1 ppm have been reported. It is obvious that, for good mass accuracies, the peaks must be baseline resolved and resolution plays an essential role. For the present example, a mass resolving power of 5000 seems to be quite acceptable. In the case of the [M+H]+ + 1 isotope peak, the situation becomes somewhat more complex for molecules containing nitrogen, sulfur or carbon. Figure 1.5 D illustrates at a mass resolving power of 500000 the contribution of... 

The particularity of the LIT-orbitrap instrument is the independent operation of the orbitrap and the LIT. Because high resolution requires longer transient time, further data can already be collected in the LIT at the same time. As an example accurate mass measurements of the precursor ion can be performed in the orbitrap while MS and MS spectra are recorded with the linear ion trap. The LIT-orbitrap has less resolution than a FT-ICR instrument with similar duty cycle, but its maintenance costs are far lower than for the FT-ICR. Both instruments will have a major impact in mainly qualitative analysis of low molecular weight compounds and macromolecules. 

Advances in high resolution mass analyzers (TOF, FT-ICR, orbitrap) have greatly improved the detection and identification of metabolites based on accurate mass measurements. In single MS mode accurate mass determination is mainly used to differentiate between isobaric ions. Combined with LC-MS, it allows the detection of predicted metabolites by performing extracted ion current profiles... 

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... 

The Orbitrap-based systems have emerged as the newest option for LC-HRMS. When configured as hybrid linear trap-Grbitrap (LTQ-Orbitrap), the systems are conceptually similar to Q-TOF in that mass analyzer 1 is nominally a unit mass analyzer, and mass analyzer 2 is capable of high resolution. These systems are capable of either LC-HRMS or LC-MS/HRMS operation. A new variant on the commercial Orbitrap, the Exactive, is expected to be released in late 2008. This system, which consists only of the single mass analyzer, has shown promising results in early assessment of quantitation by LC-HRMS (Bateman et al., 2008). 

The commercially available stand-alone LITs, marketed under the name LTQ, are made of four hyperbolic cross-sectional rods (Fig. 1.25). Since ions are trapped in an axial mode as opposed to central trapping on 3D ion traps, LTQs have been successfully coupled with Orbitrap and FTICR for achieving high-resolution capabilities (Peterman et al., 2005 Sanders et al., 2006) (Chapter 5). Functional improvements in 2D traps over 3D traps include 15 times increase in ion storage capacity, 3 times faster scanning, and over 50% improvement in detection efficiency and trapping efficiency. 

The LTQ-Orbitrap has resolution and mass accuracy performance close to that of the LTQ-FTICR. As shown in Table 5.3 (column 4), LTQ-Orbitrap accurate mass measurements, using external calibration, for a set of 30 pharmaceutical compounds resulted in less than 2.3 ppm error. The data were acquired with a 4-min, 1-mL/min-flow-rate, positive-mode LC-ESI-MS method where all measurements were performed within 5h from mass calibration. Mass accuracies below 2-3 ppm, and often below 1 ppm, can be routinely achieved in both the positive- and negative-ion mode (Table 5.3, columns 4 and 5). The long-term mass stability of the LTQ-Orbitrap is not as consistent as observed for the LTQ-FTICR-MS, and the Orbitrap requires more frequent mass calibration however, mass calibration is a routine procedure that can be accomplished within 5-10 min. Figure 5.7 displays a 70-h (external calibration) mass accuracy plot for three negative ions collected with a LTQ-Orbitrap where the observed accuracy is 2.5 ppm or better with little mass drift for each ion. Overall, for routine accurate mass measurements on the Orbitrap, once-a-week calibration (for the desired polarity) is required however, considering the ease of the process, more frequent external calibration is not a burden. 

Schmid, D. G., Grosche, P., Bandel, H., and Jung, G. (2000). FTICR-mass spectrometry for high-resolution analysis in combinatorial chemistry. Biotechnol. Bioeng. 71 149-161. Scigelova, M., and Makarov, A. (2006). Orbitrap mass analyzer—Overview and applications in proteomics. Proteomics 6 (Suppl. 2) 16-21. 

Ruan, Q., Peterman, S., Szewc, M. A., Ma, L., Cui, D., Humphreys, W. G., and Zhu, M. (2006). Metabolite detection and characterization by high-resolution orbitrap mass spectrometry Application of mass defect and product ion filtering techniques. In Proceedings of the 54th ASMS Conference on Mass Spectrometry and Allied Topics, Seattle, WA. 

Technological advances of ion-trap mass spectrometers are the ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and the recently released technique, the Orbitrap Fourier transform mass spectrometry (Hu et al., 2005), which enable the determination of molecular formulae with a high mass resolution and mass accuracy in mixtures. Today these ion-trap mass spectrometers are most frequently coupled with atmospheric pressure ionization (API) techniques such as electrospray ionization (ESI) (e.g., Fievre et al., 1997 Qian et al., 2001 Kujawinski et al., 2002 Llewelyn et al., 2002 Stenson et al., 2002,2003 Fard et al., 2003) or matrix-assisted laser desorption/ionization (MALDI) (e.g., Solouki et al.,... 

Accordingly, Gordon et al. used synthetic reference compounds for metabolites of bemesetron (MDL 72,222) to evidence proposed structures (Table 7) [37], However, in contrast to the IT and SQ analysers Chen et al., He et al. and Gordon et al. used, more modem mass spectrometers providing high-resolution equipment, e.g. Orbitrap, FT-ICR or double time-of-flight (TOF-TOF), would allow more adequate and precise identification by determination of the accurate mass. 

With respect to MS equipment significant performance improvements are promised by the use of most modem mass analysers (e.g. Orbitrap, FT-ICR, TOF-TOF) that provide highest resolution and mass accuracy important for, e.g. in-depth elucidation of biotransformation. 

Manicke N, Dill A, Ifa D, Cooks R (2010) High-resolution tissue imaging on an orbitrap mass spectrometry by desorption electrospray ionization mass spectrometry. J Mass Spectrom 45 223-226. doi 10.1002/jms,1707... 

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