Orbitrap mass analyser

However, most modem highly accurate time-of-flight (TOF), Fourier-transform ion cyclotron resonance (FT-ICR) and Orbitrap mass analysers [107] have not been reported for TA analysis so far and are thus not discussed in this chapter. 

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. 

A.A. MAKAROV describes a new type of mass analyser the orbitrap. The orbitrap is a high-performance ion trap using an electrostatic quadro-logarithmic field [5,69]. 

Hu, Q., Makarov, A., Noll, R.J. and Cooks, R.G. (2004) Application of the orbitrap mass analyser to biologically relevant compounds. Proceedings of the 52nd ASMS conference, Nashville, Tennessee, May 23-27. 

Orbitrap analyser a mass analyser that store the ions in a quadro-logarithmic field. The ions are selectively detected according to their m/z values using their induced current. The treatment of this current by a Fourier transform yields their mass-to-charge ratios. It is an analyser with very high-resolution capacity. 

From the time of the second edition published in 2001 until now, much progress has been achieved. Several techniques have been improved, others have almost disappeared. New atmospheric pressure desorption ionization sources have been discovered and made available commercially. One completely new instrument, the orbitrap, based on a new mass analyser, has been developed and is now also available commercially. Improved accuracy in low-mass determination, even at low resolution, improvements in sensitivity, better detection limits and more efficient tandem mass spectrometry even on high-molecular-mass compounds are some of the main achievements. We have done our best to include them is this new edition. 

Orbitrap, which was introduced into the market in 2005, is a new type of mass analyser, operating by radially trapping ions about a central spindle electrode. An outer barrel-like electrode is coaxial with the inner spindle-like electrode and mass/ charge values are measured from the frequency of harmonic ion oscillations, along... 

The Orbitrap is a new high-resolution mass analyser invented by Alexander Makarov (2000). An inner spindle electrode is enclosed by two electrodes in a small device of only a few centimetre length. Ions are injected into the Orbitrap... 

Hardman and Makarov, 2003), making the LTQ-Orbitrap especially suitable for small-molecule analyses. For most compounds, the relative intensities of ions in Orbitrap mass spectra are very similar to those spectra from LTQ (IT scan) (Fig. 5.5) (Sanders et al., 2005). As discussed above, this feature becomes very important for building MS/MS libraries and subsequent library searches for related structures (i.e., metabolites, structural analogues, degradants, etc.). Also highlighted in Fig. 5.5 are the excellent mass accuracies observed in the MS/MS mode, even for some very minor fragments. 

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. 

The orbitrap is an electrostatic ion trap that uses the Fourier transform to obtain mass spectra. This analyser is based on a completely new concept, proposed by Makarov and described in patents in 1996 [26] and 2004 [27], and in Analytical Chemistry in 2000 [28], A third patent describes a complete instrument including an atmospheric pressure source [29], Another article was also published with Cooks in 2005 [30]. The first commercial instrument was introduced on the market by the Thermo Electron Corporation in June 2005. 

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. 

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... 

Besides this spatial separation method using successive analysers, tandem mass spectrometry can also be achieved through time separation with a few analysers such as ion traps, orbitrap and FTICR, programmed so that the different steps are successively carried out in the same instrument. This method was described in the case of the ion traps and FTMS in Chapter 2. The maximum practical number of steps for these instruments is seven to eight. In these instruments the proportion of ions transmitted is high, but at each step the mass of the fragments becomes lower and lower. 

In comparison with NMR, mass spectrometry is more sensitive and, thus, can be used for compounds of lower concentration. While it is easily possible to measure picomoles of compounds, detection limits at the attomole levels can be reached. Mass spectrometry also has the ability to identify compounds through elucidation of their chemical structure by MS/MS and determination of their exact masses. This is true at least for compounds below 500 Da, the limit at which very high-resolution mass spectrometry can unambiguously determine the elemental composition. In 2005, this could only be done by FTICR. Orbitrap appears to be a good alternative, with a more limited mass range but a better signal-to-noise ratio. Furthermore, mass spectrometry allows relative concentration determinations to be made between samples with a dynamic range of about 10000. Absolute quantification is also possible but needs reference compounds to be used. It should be mentioned that if mass spectrometry is an important technique for metabolome analysis, another key tool is specific software to manipulate, summarize and analyse the complex multivariant data obtained. 

Along with advances in various ionization sources, significant improvements have been made in the area of mass analyzers. Mass analyzers can be differentiated based on several attributes such as scan speed, duty cycle, mass resolution, mass range, and cost [126], The most common analyzers used for metabonomics analyses include the quadrupole and TOF-based analyzers [125-127], Some other analyzers that have been reported for use in MS-based metabonomics analyses are the ion traps, Orbitraps, and Fourier transform mass spectrometers [128,129],... 

Analyze by direct infusion using a Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer (ThermoFisher Scientific). AH analyses are performed with resolving power set to 140,000, four microscans for 30 s. 

The fundamental process of MS/MS (in a tandem mass spectrometer) is that a particular precursor ion is fragmented (decomposed) into a smaller product ion accompanied by the loss of a neutral fragment. The precursor ion is usually selected in the first analyzer, reacted by some means in a specialized chamber (see below) to produce product ions that are then separated in a second analyzer, hence the terms mass spectrometry/mass spectrometry and tandem mass spectrometry. As discussed later, precmsor and product ion analyses can be separated in space, using sequential analyzers that are either of the same type or in hybrid configurations, or separated in time in the latter the two analytical processes are carried out sequentially, within the same analyzer. There are several MS/MS instrument combinations, including QqQ, QIT, LIT, TOF/TOF, QTOF, LlT-orbitrap, and LIT-FT-ICRMS. 

For many years double focusing sector instruments were the instruments of choice for highly accurate and precise (within lppm) measurements of molecular mass, used to determine molecular compositions of unknown compounds or at least limit the possibilities to a small number. This role is now usually fiUed by upper-end TOF analyzers (less expensive, superior ease of use, but lower accuracy and precision) and by FTICR and Orbitrap instruments (more expensive but higher RP possible). Magnetic sector instruments are still used by the petroleum industry in type analysis (see Preface), and also for GC/HRMS quantitation as mentioned above, since TOF, FTICR and Orbitrap instruments do not posses the necessary combination of figures of merit for such trace quantitative analyses. 

As the frequency of ion motion can be determined with high precision, the mass determination results with high accuracy below 1 ppm and very high mass resolution above 500000 (Figure 2.190). The mass precision and resolution depends on the measurement time of the trapped ions. Orbitrap MS systems are applied in LC-MS since many years for proteomics and metabolomics especially in life sciences, but also show its high capabilities in the small molecular domain for multi-residue trace analyses of, for example, pesticides or drugs, both in LC-MS (Fiirst and Bernsmann, 2010 Kaklamanos et al., 2013) and GC-MS applications (Peterson et al, 2009, 2010). 

With its capabilities in high mass resolution combined with the uncompromized detection sensitivity and speed, the analytical advantages of the Orbitrap analyser for GC-MS are developing quickly into a combined targeted and non-targeted trace analysis. 

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