The Q-TOF

The second case (Fig 3.10) (Varian) is strongly analogous to that just described The only difference lies in the collision cell, that in this case is hexapolar and uses a quadrupole mass filter for ion isolation. 

Finally, the instrumental arrangement employed in the third case (Fig 3.11) (Bruker Daltonics) is more complex The system allows to use both ESI and MALDI sources. Along the ion pathway, storage hexapole, quadrupole mass filter for ion selection, and collisional hexa-pole cells are present before the ion injection inside the ICR cell. 

In all three instrumental configurations, it is possible to induce decomposition of the ion trapped inside the ICR cell not only by collisional experiments, but also by interaction with slow electrons (electron capture dissociation, ECD) or by irradiation with an infrared (IR) laser beam (infrared multi photon dissociations, IRMPD). Experiments of this type (mainly devoted to polypeptide identification) allow to maintain the high-vacuum conditions inside the ICR cell, which are necessary to achieve the high-resolution conditions. 

In the case of Orbitrap, an ion optics strongly analogous to that reported in Fig. 3.12 is employed. The cryomagnet and the ICR cell are substituted by the curved quadrupole and the Orbitrap cell, as described in Section 2.3.5. 

Besides the FT-MS-based instruments, which are able to obtain specificity through either MS/MS or accurate mass measurements, another system is commercially available, based on the use of 

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The term Q/TOF is used to describe a type of hybrid mass spectrometer system in which a quadrupole analyzer (Q) is used in conjunction with a time-of-flight analyzer (TOP). The use of two analyzers together (hybridized) provides distinct advantages that cannot be achieved by either analyzer individually. In the Q/TOF, the quadrupole is used in one of two modes to select the ions to be examined, and the TOF analyzer measures the actual mass spectrum. Hexapole assemblies are also used to help collimate the ion beams. The hybrid orthogonal Q/TOF instrument is illustrated in Figure 23.1. 

Scanning techniques are carried out differently with such hybrid instruments as the triple quadrupole analyzer, the Q/TOF (quadrupole and time-of-flight), and double magnetic-sector instruments. 

As with the Q-ToF instrument, only two types of MS-MS experiment are available with the ion-trap, i.e. the product-ion scan and selected-decomposition monitoring, as described in Sections 3.4.2.1 and 3.4.2.4, respectively. 

The ion-trap and Q-ToF instruments are, because of the way that they operate, unable to carry out precursor-ion scans. Computer manipulation of data generated during product-ion scans of the Q-ToF system, however, can yield equivalent data to that produced directly by precursor-ion scans on other instruments and an evaluation of this software-based approach has been carried out [14],... 

An MS-MS instrument only relatively recently made available commercially for LC-MS applications is the Q-ToF system, i.e. the combination of a quadrupole mass analyser for precursor-ion selection and a time-of-fiight analyser for production detection. As described earlier in Section 3.4.1.4, this instrument has the... 

The LCQ and LCQ DECA are products of Thermo Electron Corporation (San Jose, CA) the Q-TOF is a product of Waters (Beverly, MA) the QSTAR, ProQUANT, and ProICAT are products of Applied Biosystems (Foster City, CA) and Spectrum Mill and the MSD TRAP XCT are products of Agilent Technologies (Palo Alto, CA). 

Fig. 4.56. Schematic of the Q-TOF Ultima with ESI ion source in MS/MS mode. The TOF analyzer has a double reflector for higher resolution. Courtesy of Waters Corporation, MS Technologies, Manchester, UK.

Cox, K., Clarke, N., Dunn-Meynell, K., Korfmacher, W., Lin, C. C., White, R. and Cayen, M., Use of the Q-Tof, LCQ and Triple Quadrupole Mass Spectrometers for Metabolite ID in Support of Drug Discovery, American Society for Mass Spectrometry 1999 Conference Abstract, Dallas, TX, USA, 1999. 

Processing using the Q-Tof, American Society for Mass Spectrometry 1999 Conference Abstract, Dallas, TX, USA, 1999. 

Figure 1.14. MRM chromatograms of SCH 29851 (383.0. 337.0) and SCH 34117 (311.1 259.1) obtained using Sciex API 3000 (triple-stage quadrupole) and Sciex QSTAR pulsar (Q-TOF). Comparison of MRM chromatograms of SCH 29851 and SCH 34117 obtained at the LOQ (1 ng/mL) using the API 3000 mass spectrometer with those from the Q-TOF mass spectrometer indicated that the S/N ratio is at least 10-20 times better on the API 3000 mass spectrometer. However, the MRM chromatograms from the API 3000 mass spectrometer do not provide the option to further examine the MS/MS spectra whereas the full-scan MS/MS spectra from a Q-TOF based quantitative bioanalysis assay allows one to easily eliminate any questions about false-positive data. (Rephnted with permission from Yang et a ., 2001b.)...

Morris, H. R., Paxton, T., Panico, M., McDowell, R., and Dell, A. (1997). A novel geometry mass spectrometer, the Q-TOF, for low-femtomole/attomole-range biopolymer sequencing. J. Protein Chem. 16 469-479. 

Over the years, the Q-TOF instrumentation has become an important mass spectrometer of choice for scientists working in the drug metabolism arena. This is due to the fact that Q-TOF offers very high sensitivity in the full-scan MS and... 

Certain software algorithms such as the one mentioned previously uses the high-quality exact mass data from the high-resolution TOF systems to report calculated elemental compositions within the results browser. Good scientific practice mandates the use of an internal reference or lock mass to obtain valid exact mass measurements (sub-5-ppm). Exact mass measurement gives greater confidence in the confirmation of expected metabolites and allows the prediction of the elemental composition of unknowns. The Q-TOF mass spectrometer can be set up to automatically acquire exact mass LC-MS and exact mass MS-MS data to within the recommended mass accuracy guidelines of 5 ppm. 

Both of the above examples illustrate that the sensitivity of the MDF method, in general, is comparable to PIS analysis and better than NLS methods (Figs 6.9 and 6.10). The sensitivity of the MDF method is attributed at least in part to the full-scan capability of high-resolution mass spectrometers such as the Q-TOF and LTQ-FTICR, which could be several times more sensitive than full-scan analysis by a triple-quadrupole mass spectrometer (Kostiainen et al., 2003). 

Comparison of triple-quadrapole and Q-TOF use in these type of studies was reported [22]. While similar sensitivity can be achieved, the selectivity of the Q-TOF is better due to its high resolving power, thereby minimizing isobaric interferences. Bateman et al. [23] reported a novel mode of operation of a (J-TOF instrument for precursor-ion analysis of phosphoproteins. The first-stage quadrapole is operated in radiofrequency-only mode, serving as a wide-band ion-transmission... 

Triple-quadrapole, ion-trap, and Q-TOF instruments were compared in MS and MS-MS with product-ion, neutral-loss, and precursor-ion analysis modes for the profiling of the Asn -A-glycan of the a-unit of ovine luteinizing hormone [86]. More than 20 glycoforms were detected and identified. The Q-TOF allowed the lowest sample consumption, but all three instruments contributed to the profiling study. 

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