Q-TOF hybrid instrument

Fig. 11.27. (a) NanoESI-CID-MS/MS spectrum of the [M-H] ion, m/z 2246.9, of a modified nonasaccharide obtained in a Q-TOF hybrid instrument and (b) proposed structure with fragments indicated. Reproduced from Ref. [137] by permission. Elservier Science, 2001. 

Note SRM is preferably performed on triple quadrupole, quadrupole ion trap, and Q-TOF hybrid instruments due to their ease of setting up the experiment and to their speed of switching between channels if monitoring of multiple reactions plays a role. 

Two recent instrumental innovations can be applied to further assist in the interpretation of product-ion mass spectra. As discussed above, the MS-MS capabilities of an ion-trap system allow the step-wise fragmentation of an analyte, facilitating the interpretation of the product-ion information and the fragmentation reactions involved. The use of a Q-TOF hybrid instrument allows accurate mass determination (at an accuracy of 5 ppm) of the product ions observed, which also facilitates the interpretation of the product-ion mass spectra. 

This chapter provides brief descriptions of analyzer layouts for three hybrid instruments. More extensive treatments of sector/TOF (AutoSpec-TOF), liquid chromatography/TOF (LCT or LC/TOF with Z-spray), and quadrupole/TOF (Q/TOF), are provided in Chapters 23, 22, and 21, respectively. 

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. 

Chapter 23 Hybrid Quadrupole Time-of-Flight (Q/TOF) Instruments... 

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. 

Hybrid Mass Spectrometer A tandem mass spectrometer comprised of multiple mass analyzers of different types. A Q-TOF is a hybrid, but a triple quadmpole is not. Ideally, a hybrid instrument harnesses the best features of each mass analyzer type to produce a system perhaps greater than the sum of the parts. 

Recent innovations in mass spectrometry have provided incorporation of two, three, and four analyzers into commercially available tandem instruments. In addition, different mass analyzers may be combined to form a hybrid mass spectrometer such as the quadrupole-TOF (Q-TOF). Various types of tandem mass spectrometers include the quadruopole-TOF, time-of-flight-time-of-hight (TOF-TOF), triple-quadrupole, and Orbitrap-FTICR configurations. 

The ability of this ionization method for the determination of very high molecular weights is illustrated in Figure 1.26 [68], The spectrum displayed is obtained from assemblies of vanillyl alcohol oxidase containing respectively 16 and 24 proteins. The spectrum was obtained with a hybrid quadrupole TOF instrument, Q-TOF Micromass, equiped with a micro-ESI source. To obtain such a spectrum one needs not only a mass spectrometer with sufficient mass range and resolution, but also high skill in protein purification. 

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. 

Many instrumental set-ups and geometries have been explored. In triple quadrupole mass spectrometry, the first quadrupole selects the parent ion of interest, the second works as a collision cell to fragment the parent ion, and the third isolates the proper product ion. A hybrid type is the quadrupole time-of-flight (Q-TOF) instrument. 

Traditional detectors (i.e., FID electron capture detector, BCD nitrogen-phosphorous detector, NPD) supply only retention data. However, in many cases this is not enough for proper identification of analytes. Application of GC coupled with an MS detector gives much more information (i.e., the mass spectmm of each compound). GC-MS is a well known and frequently used technique that combines the highly effective separation of GC with the high sensitivity and selectivity of MS. Moreover, improvements in analytical instruments based on different types of mass analyzers (ion trap, quadrupole, and TOF) and the development of hybrid Q-TOF has enhanced the analytical capabilities of modem hardware. Different kinds of mass spectrometers are presented in Table 14.2 [119]. 

A variety of tools are available for the detection and characterization of the metabolites. Unless advanced data-acquisition strategies (Ch. 10.4.4) are applied, at least two LC-MS analyses are required. The first injection is performed in full-spectrum LC-MS mode, preferable using an MS system with improved full-spectrum sensitivity, such as (linear) ion trap and time-of-flight (TOP) instruments. The analysis of a blank extract next to real samples greatly facilitates peak detection and avoids further work on endogenous peaks. The data are processed to find the relevant /w/z-values of potential metabolites. These /w/z-values are used as precursor ion m/z in a subsequent (time-scheduled) product-ion LC-MS-MS analysis. Again, instruments with improved full-spectrum sensitivity, such as ion-traps, quadrapole-linear ion trap hybrids (Q-LIT), or quadrapole-TOF hybrids, are favourable. 

Zhou and Johnston [55] reported protein characterization by capillary isoelectric focussing (CIEF) on-hne coupled to RPLC-MS. Direct coupling of CIEF to ESl-MS is limited by interferences by the ampholytes. Inserting RPLC in-between can help removing these interferences. CIEF is performed in combination with a microdialysis membrane-based cathodic cell to remove the ampholyte and to collect protein fractions by stop-and-go CIEF prior to transfer to a 5><0.3-pm-ID C,8 trapping colunm and RPLC separation on a 50><0.3-pm-ID C4 column. The separation is performed using an acetonitrile-water gradient (0.1% acetic acid). ESI-MS is performed on a quadrupole-TOF hybrid (Q-TOF) instrument. 

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