Hybrid instrument spectrometry

In mass spectrometers, ions are analysed according to the ml7. (mass-to-charge) value and not to the mass. While there are many possible combinations of technologies associated with a mass-spectrometry experiment, relatively few forms of mass analysis predominate. They include linear multipoles, such as the quadrupole mass filter, time-of-flight mass spectrometry, ion trapping forms of mass spectrometry, including the quadrupole ion trap and Fourier-transform ion-cyclotron resonance, and sector mass spectrometry. Hybrid instruments intend to combine the strengths of the component analysers. 

TOF analyzers are especially compatible with MALDI ion sources and hence are frequently coupled in aMALDI-TOF configuration. Nevertheless, many commercial mass spectrometers combine ESI with TOF with great success. For proteomics applications, the quadrupole TOF (QqTOF) hybrid instruments with their superior mass accuracy, mass range, and mass resolution are of much greater utility than simple TOF instruments.21,22 Moreover, TOF instruments feature high sensitivity because they can generate full scan data without the necessity for scanning that causes ion loss and decreased sensitivity. Linear mode TOF instruments cannot perform tandem mass spectrometry. This problem is addressed by hybrid instruments that incorporate analyzers with mass selective capability (e.g., QqTOF) in front of a TOF instrument. 

Finally, it is important to note there are many other instruments and configurations that are often referred to as tandem mass spectrometers. There are hybrid instruments that use another form of mass separation, time-of-flight (TOF) mass spectrometry. TOF mass spectrometry separates ions based on the time it takes to... 

Yost, R. A. Boyd, R. K. 1990. Tandem mass spectrometry quadrupole and hybrid instruments. Methods Enzymol., 193,154-200. 

Boyd, R.K., Tandem mass spectrometry quadropole and hybrid instruments, Metftodi nzymo/. 193, 154-200, 1990 Jonscher, K.R. and Yates, J.R., 111, The quadrupole ion trap mass spectrometry — a small solution to a big challenge. Anal. Biochem. 244, 1-15, 1997 Chemushevich, I.V., Loboda, A.V., and Thomson, B.A., An introduction to quadrupole-time-of-flight mass spectrometry, J. Mass Spectrom. 36, 849-865, 2001 Ens, W. and Standing, K.G., Hybrid quadrapole/time-of-flight mass spectrometers for analysis of biomolecules. Methods Enzymol. 402,49-78, 2005 Payne, A.H. and GUsh, G.L., Tandem mass spectrometry in quadrupole ion trap and ion cyclotron resonance mass spectrometers. Methods Enzymol. 402, 109-148, 2005. 

The second disadvantage is the requirement for a trained operator. The marriage of HPLC and mass spectrometry is now commonplace but the extra dimension and complexity of this hybrid instrument requires training even for an experienced chro-matographer. 

The types of tandem mass spectrometers capable of performing MS/MS experiments fall into two basic categories tandem in space and tandem in time. Tandem-in-space instruments have discrete mass analyzers for each stage of mass spectrometry examples include multisector, triple-quadru-pole, and hybrid instruments (instruments having mixed types of analyzers such as a magnetic sector and a quadrupole). Tandem-in-time instruments have only one mass analyzer where each stage of mass spectrometry takes place in the same analyzer but is separated in time via a sequence of events. Examples of this type of instrument include Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers and quadrupole ion traps, described in Chapter 3. 

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. 

Techniques and Instrumentation of Mass Spectrometry 10.2.2.5 Hybrid Instruments... 

Tandem Mass Spectrometry with Hybrid Instruments... 

The newer MS experiments in a data-dependent acquisition mode provide the MS and MS" data from a single injection. Accurate mass measurements, software-assisted data acquisition, and processing methods have been very useful for metabolite detection and identification. In addition, when MS is combined with other analytical techniques such as derivatization, H/D exchange, and stable isotope labeling have been proven very useful for structural characterization of unusual, uncommon, and difficult metabolites. Further, the flexibility and broad applications of mass spectrometry have allowed for the creation of hybrid instruments and coupling to other powerful analytical techniques, most notably nuclear magnetic resonance (NMR), to further enhance the utility in the field of drug metabolism. 

Most continuous ion sources are suited to oa-TOF-MS it can also be used effectively as the final mass analyzer in hybrid instruments which combine two mass spectrometers in an approach called tandem mass spectrometry or MS/MS. 

It is clear that mass spectrometry imaging has great potential as a comprehensive analysis technique for endogenous peptides, particularly with a hardware configuration as evaluated in this chapter, where MALDI produced ions are analyzed in an ion trap - Orbitrap hybrid instrumentation. A single experiment can provide high mass accuracy data in combination with the spatial distribution of peptides in the tissue sample. With MS/MS experiments the molecular identity (accurate mass measurements complemented with MS" sequence data) can be confirmed firom a single or few scans only and from a few laser shots in total. 

Musharraf SG, Ali A, Ali RA, Yousuf S, Atta-ur-Rahman, Choudhary MI (2011) Analysis and development of structure-fragmentation relationship in withanolides using an electrospray ionization quadrapole time of flight tandem mass spectrometry hybrid instrument. Rapid Commun Mass Spectrom 25 104—114... 

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