Linear Orbitrap

In principle, it would be possible to perform multistage mass spectrometry like in an ICR analyzer although with no gas CID would of course not be possible, but other dissociation methods could be employed. There might, however, be technical issues. At the time of writing, fragmentation is performed in the linear QIT preceeding the orbitrap in Thermo Fischer Scientific s instrument. Both pulsed and continuous ion sources can be employed. There are several ion sources that can be employed with Thermo Fischer Scientific s orbitrap. 

J. R. Yates, D. Cociorva, L. Liao, and V. Zabrouskov. Performance of a Linear Ion Trap-Orbitrap Hybrid for Peptide Analysis. Anal. Chem., 78(2006) 493-500. 

A. Makarov, E. Denisov, A. Kholomeev, W. Balschun, O. Lange, K. Strupat, and S. Homing. Performance Evaluation of a Hybrid Linear Ion Trap/Orbitrap Mass Spectrometer. Anal. Chem., 78(2006) 2113-2120. 

Fig. 1.30 Schematic of the linear ion trap (LIT)-orbitrap (LTQ orbitrap, Thermo). One of the specificities of the system is that the LIT has two detectors. Therefore the LIT can perform various experiments at the same time. Adapted with permission from reference [76].

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. 

A similar approach using accurate mass measurements and predictive fragmentation sofiware was also applied for the examination of the human microsomal metabolism of nefazodone using a linear ion trap-orbitrap hybrid mass spectrometer. Based on a single LC-MS run, using data-dependant acquisition, 15 metabolites of nefazodone could be identified in MS and MS/MS with a mass accuracy better than 3 ppm. 

Makarov, A. Denisov, E. Kholomeev, A. Balschun, W. Lange, O. Strupat, K. Homing, S. Performance evaluation of a hybrid linear ion trap/ orbitrap mass spectrometer. Anal. Chem. 2006, 78, 2113-2120. 

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). 

Ruan, Q., Peterman, S., Szewc, M. A., Ma, L., Cui, D., Humphreys, W. G., and Zhu, M. (2008). An integrated method for metabolite detection and identification using a linear ion trap/Orbitrap mass spectrometer and multiple data processing techniques Application to indinavir metabolite detection. J. Mass Spectrom. 43 251-261. 

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,... 

Figure 5.5. Buspirone MS/MS (m/z 386) spectra collected using a (a) linear ion trap, (b) FTICR operated in the regular-scan mode, (c) FTICR operated in the wide -scan mode, and fdj Orbitrap.

Figure 5.8. Synthetic standards of five hydroxylated buspirone metabolites spiked into rat plasma and analyzed on a 4.6 x 150-mm YMC-ODS AQ S3 column at a flow rate of 1 mL/min LC-MS chromatograms obtained following injection of 10 pg of each metabolite on column (a) Orbitrap and (b) linear ion trap. MS/MS (m/z 402) spectra of oxa-buspirone metabolite (Rt = 7.4min) (c) Orbitrap at 10pg on column, (d) Orbitrap at 100pg on column, and (e) linear ion trap at 10 pg on column.

Macek, B., Waanders, L. F., Olsen, J. V., and Mann, M. (2006). Top-down protein sequencing and MS3 on a hybrid linear quadrupole ion trap-orbitrap mass spectrometer. Mol. Cell. Proteomics 5 949-958. 

McAlister, G. C., Phanstiel, D., Good, D. M., Berggren, W. T., and Coon, J. J. (2007). Implementation of electron-transfer dissociation on a hybrid linear ion trap-orbitrap mass spectrometer. Anal. Chem. 79 3525-3534. 

Peterman, S. M., Duczak, N., Jr., Kalgutkar, A. S., Lame, M. E., and Soglia, J. R. (2006). Application of a linear ion trap/orbitrap mass spectrometer in metabohte characterization studies Examination of the human liver microsomal metabolism of the non-tricyclic antidepressant nefazodone using data-dependent accurate mass measurements. J. Am. Soc. Mass Spectrom. 17 363-375. 

Yates, J. R., Cociorva, D., Liao, L., and Zabrouskov, V. (2006). Performance of a linear ion trap-Orbitrap hybrid for peptide analysis. Anal. Chem. 78 493-500. 

Cells, rat liver Modified Blight and Dyer extraction, fractionation with HPLC (C18) MS ESI hybrid linear ion trap Orbitrap 2 fmol/pl (PA and PS) 45 (44)... 

Miyaguchi H, Inoue H (2011) Determination of amphetamine-type stimulants, cocaine and ketamine in human hair by liquid chromatography/linear ion trap-Orbitrap hybrid mass spectrometry. Analyst 136(17) 3503—3511. doi 10.1039/c0an00850h... 

Figure 2.37 shows the scheme of the first commercially available orbitrap instrument. It is somewhat different from the one previously described. First, there is an linear ion trap (LIT) that can be used for ion storage and ejection to the orbitrap by axial ejection, or independently used as a linear trap by radial ejection. It is possible to inject all the ions from the LIT, or selected ones, or product ions from the MS" operations of the LIT. The normal acquisition cycle time in the orbitrap is 1 second. 

Some mass spectrometers combine several types of analysers. The most common ones include two or more of the following analysers electromagnetic with configurations EB or BE, quadrupoles (Q), ion traps (ITs) with Paul ion traps or linear ion traps (LITs), time-of-flight (TOF), ion cyclotron resonance (ICR) or orbitrap (OT). These are named hybrid instruments. The aim of a hybrid instrument is to combine the strengths of each analyser while avoiding the combination of their weaknesses. Thus, better performances are obtained with a hybrid instrument than with isolated analysers. Hybrids are symbolized by combinations of the abbreviations indicated in the order that the ions travel through the analysers. 

Vallverdu-Queralt, A. Jauregui, O. Medina-Remon, A. Andres-Lacueva, C. Lamuela-Raventos, R.M. 2010. Improved characterization of tomato polyphenols using liquid chromatography/electrospray ionization linear ion trap quadrupole Orbitrap mass spectrometry and liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Comm. Mass Spectrom. 24 2986-2992. 

---