Mass spectrometers FT/ICR

Concerning the first field of application, the kinetics and equilibrium constants for several halide transfer reactions (equation 1) were measured in a pulsed electron high pressure mass spectrometer (HPMS)4 or in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR)5. From measurements of equilibrium constants performed at different temperatures, experimental values were obtained for the thermochemical quantities AG°, AH° and AS° for the reaction of equation 1. The heat of formation (AH°) of any carbocation of interest, R+, was then calculated from the AH0 of reaction and the AH° values of the other species (RC1, R Cl and R +) involved. 

Next to CE, on-line coupling of capillary lEF and MS is attractive. For protein characterizatiorr, CIEF-MS on a Fourier-transform ion-cyclotron resonance mass spectrometer (FT-ICR-MS) irrstrament was pioneered by the group of Smith [99-100]. They demonstrated the high-resolution analysis of E. coli proteins, reveahng >400 proteins (2-100 kDa) from an injection of only 300 ng. 

Given the complexity of the oligonucleotide MS and MS-MS spectra, the application of high-resolntion instmments like Fonrier-transform ion-cyclotron resonance mass spectrometers (FT-ICR-MS) is beneficial. While some initial results were reported in the mid-1990s, e.g., [37-38], the fieqnent ntilization of FT-ICR-MS in oligonucleotide characterization is more recent (Ch. 22.3.3). 

Fig. 20.1. Scheme of the instrumental setup for the Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR-MS)... 

A Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS) can be considered as an ion trap system, where the ions are trapped in the magnetic field rather than in a quadrapole electric field. The ICR cell is a cubic or cylindrical cell positioned in a strong magnetic field B (up to 15 T). The cell consists of two opposite trapping plates, two opposite excitation plates, and two opposite receiver plates (Fig. 4.6). Extreme high vacuum should be achieved in the cell, e.g., 10 mbar. 

Van Rooij and co-workers [126] used MALDI on an external ion source Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS) to analyse the block length distributions of triblock polymers of poly(oxypropylene) and poly(oxyethylene). For the first time, detailed and accurate molecular weight data were obtained on a complex sample using this methodology, which independently validated the data provided by the manufacturer. The experimentally verified random coupling hypothesis proved the validity of the methodology. 

Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR)... 

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.,... 

The quadrupole ion trap is seen as a compact and less expensive alternative to FT-ICR mass spectrometers employed for gas-phase metal ion chemical and mass analysis [28,29]. Although lacking the high mass resolving powers available in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), the quadrupole ion trap has been investigated by using nonselective and resonance-selective ionization of ablated metal samples. 

Fourier transform ion cyclotron mass spectrometry (FT-ICR-MS) instrumentation offers excellent sensitivity, accuracy (<1 ppm), and high mass resolution (>1,000,000) (Table 10.2). However, because of being too expensive, difficult to use, and not compatible with conventional HPLC columns and flow rates, FTMS has not been frequently used in pharmaceutical research. This changed with an introduction of a hybrid instrument consisting of a linear ion-trap mass spectrometer compatible with LC and an ion-cyclotron-resonance (ICR) detector. Such a hybrid instrument is compatible with conventional HPLC and allows for acquisition of accurate mass data-dependent MS" spectra. Sanders et al. [128] recently reviewed the utility of hybrid LTQ-FTMS for drug metabolism and metabonomics applications while Brown et al. [129] reviewed the metabolomics applications of FT-ICR-MS. 

Ion Cyclotron Resonance Mass Filter Like Magnetic Sector mass filters, Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass filters use magnetic fields to determine the m/g ratio of ions. Although capable of extreme mass resolution (m/Am > 100,000), these have only been recently introduced in the field of SIMS albeit in highly specialized research environments (Pahnblad et al. 2000 Todd et al. 2002 Smith et al. 2011). These are also sometimes referred to as Fourier Transform Mass Spectrometers (FT-MS). 

In the other types of mass spectrometer discussed in this chapter, ions are detected by having them hit a detector such as an electron multiplier. In early ICR instruments, the same approach was taken, but FT-ICR uses a very different teclmique. If an RF potential is applied to the excitation plates of the trapping cell (figure B 1.7.18(b)) equal to the cyclotron frequency of a particular ion m/z ratio, resonant excitation of the ion trajectories takes place (without changing the cyclotron frequency). The result is ion trajectories of higher... 

Instruments are available that can perform MS/MS type experiments using a single analyzer. These instruments trap and manipulate ions in a trapping cell, which also serves as the mass analyzer. The ion trap and fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers are examples. 

Tandem quadrupole and magnetic-sector mass spectrometers as well as FT-ICR and ion trap instruments have been employed in MS/MS experiments involving precursor/product/neutral relationships. Fragmentation can be the result of a metastable decomposition or collision-induced dissociation (CID). The purpose of this type of instrumentation is to identify, qualitatively or quantitatively, specific compounds contained in complex mixtures. This method provides high sensitivity and high specificity. The instrumentation commonly applied in GC/MS is discussed under the MS/MS Instrumentation heading, which appears earlier in this chapter. 

The kinetics study [38] utilized a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer to measure the pathway branching ratios. The ability to eject selected masses and the extremely high mass resolution of this technique ensured that the observed CD3CH2 was in fact a primary product of the reaction. Temporal profiles from this reaction are shown in Fig. 1. Noticeably absent from the mass spectrum are the cations C2D2H3 and... 

With the FT-ICR mass spectrometer it is possible to obtain high mass accuracy (about 1-5 ppm calibrated externally, 0.5-1-0 ppm if calibrated internally here an external calibration has been carried out using a tune mix containing compounds with m/z from... 

In FT-ICR mass spectrometers, ion isolation and detection occur in the same region. In fact all ions coming from the source are simultaneously excited applying a RF pulse of a... 

The ion trapping capability of the FT-ICR is much greater than the other types of mass spectrometer and ions may be trapped for several minutes under ideal conditions. 

Usually, concentration is measured as a pressure and may differ widely according to the type of mass spectrometer used. The triple quadrupole mass spectrometer may operate with pressures up to 1 x 10 1 Pa in the reaction region. At the other extreme, ion cyclotron resonance mass spectrometers operate poorly at pressures >1 X 10 4 Pa. A pressure of 1 x 10 4 Pa may be regarded as fairly high pressure for FT-ICR measurements. Converting the pressure into a more normal value of concentration means that reactions are carried out at concentrations < 10 9M (often several orders of magnitude < 10 0 M). 

The reactions of small cluster cations of copper and silver, Cu and Ag (n = 1-5), with methanol, ethanol, the two isomers of propanol, and the four isomers of butanol have been studied in a FT-ICR mass spectrometer (200). The ions were produced by FAB and exited through a small hole that aided the clustering process. Once in the cell, the ions were collisionally cooled with argon and allowed to react with the alcohols (3-100 x 10 6 Pa) for periods up to 60 s. The Cu4 ion was produced but was of insufficient abundance for reactivity studies. 

Capillary electrophoresis (CE) either coupled to MS or to laser-induced fluorescence (LIF) is less often used in metabolomics approaches. This method is faster than the others and needs a smaller sample size, thereby making it especially interesting for single cell analysis [215] The most sensitive mass spectrometers are the Orbitrap and Fourier transform ion cyclotron resonance (FT-ICR) MS [213]. These machines determine the mass-to-charge ratio of a metabolite so accurate that its empirical formula can be predicted, making them the techniques of choice for the identification of unknown peaks. 

The proton affinities of 1,2- and 1,3-butadiene and of 2-butyne have been determined by Lias and Ausloos79 using equilibrium measurements in an Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Surprisingly, they were found to be almost identical. The bimolecular reactivity of the C4FL+ cations formed from the three isomers was also reported. 

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