Hybrid quadrupole mass spectrometer

Various tandem MS instrument configurations have been developed, e.g. sector instruments, such as CBCE, CBCECB or CECBCE, and hybrid instruments, e.g. BCECQQ (B = magnetic sector analyser, E = electrostatic analyser, C = collision cell, Q = quadrupole mass spectrometer), all with specific performance. Sector mass spectrometers have been reviewed [168],... 

One of the best tools for metabolite profiling is the hybrid QTRAP MS/MS system (Applied Biosystems).119-121 While the hybrid QTRAP MS/MS was initially considered a premier tool for metabolite identification, it has more recently been seen as a tool for quantitation and metabolite profiling. Li et al.122 described the use of a hybrid QTRAP MS/MS system for discovery PK assays plus metabolite profiling in the same analytical procedure. Because QTRAP MS/MS may be used as a triple quadrupole MS system, it can be used as part of a quantitative HPLC/MS/MS system. Because QTRAP MS/MS also has linear ion trap capabilities, it can be used for metabolite screening and characterization—essentially it combines the capabilities of a triple quadrupole mass spectrometer and a linear ion trap mass spectrometer. 

Fig. 8.1.1 Simple illustrations of a various mass spectrometers, a The triple-quadrupole tandem mass spectrometer (top panel). The middle set of quadrupoles are part of the collision cell (CC) and do not perform mass separation. MSI and MS2 indicate the first and second quadrupole mass separation devices, respectively. The bold arrow shows the path of ions, b Ion-trap mass spectrometer (middle left). The charged sections of the ion trap are not elliptical as drawn, but rather hyperbolic. The diagram is also two-dimensional, whereas the ion trap is three-dimensional. The ion path is such that ions enter the device and are trapped until a specific voltage ejects these ions, c Time of Flight mass spectrometer with a Reflectron (middle left). Ions are separated by the time it takes to pass through the instrument. The Reflectron improves/focuses the ions, d Hybrid Tandem mass spectrometer (bottom). The diagram shows that a quadrupole instrument can be combined with a different type of mass spectrometer, forming a tandem hybrid instrument...

The most common types of MS/MS instruments available to researchers in food chemistry include triple quadrupole mass spectrometers and ion traps. Less common but commercially produced tandem mass spectrometers include magnetic sector instruments, Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, and quadrupole time-of-flight (QTOF) hybrid instruments (Table A.3A.1). Beginning in 2001, TOF-TOF tandem mass spectrometers became available from instrument manufacturers. These instruments have the potential to deliver high-resolution tandem mass spectra with high speed and should be compatible with the chip-based chromatography systems now under development. 

A schematic of the QQQ/LIT ion path is shown in Fig. 3.7. Similar to a typical triple-quadrupole mass spectrometer, three quadrupoles are present in a QQQ/LIT mass spectrometer. The difference between a hybrid instrument and a triple quadrupole is that Q3 can be operated in standard triple-quadrupole mode or used as a LIT. When the LIT is active, an entrance potential barrier and an exit potential barrier are created to axially contain the ions. Along with the exit and entrance barriers, a radial... 

Elemental mass spectrometry has undergone a major expansion in the past 15-20 years. Many new a, elopments in sample introduction systems, ionization sources, and mass analyzers have been realized. A vast array of hybrid combinations of these has resulted from specific analytical needs such as improved detection limits, precision, accuracy, elemental coverage, ease of use, throughput, and sample size. As can be seen from most of the other chapters in this volume, however, the mass analyzers used to date have primarily been magnetic sector and quadrupole mass spectrometers. Ion trapping devices, be they quadrupole ion (Paul) [1] traps or Fourier transform ion cyclotron resonance (Penning) traps, have been used quite sparingly and most work to date has concentrated on proof of principal experiments rather that actual applications. 

Figure 4. Effects of ion kinetic energy on the MS/MS of 5-indanol (a) MS/MS obtained on MIKES instrument with 7000 eV translational energy (b) spectrum obtained on hybrid BQ (magnet followed by quadrupole) mass spectrometer 95 eV (c) spectrum obtained with QQ (tandem quadrupole) mass spectrometer at 35 eV...

Tandem MS was applied to characterization and differentiation of the connectivity of the 0283 radical cation (mlz = 120) generated by dissociative electron ionization (El) of the l,3,4,6-tetrapentalene-2,5-dione 39. The structural assignment of the radical cation C2S as the C-sulfide ethenedithione, SCCS2 40, was based on the results of ion-molecule reactions of 0283 with nitric oxide, acetonitrile, and methyl isocyanide. The collisional activation spectra of these ion-molecule reaction products recorded on a new type of hybrid tandem mass spectrometer of sectors-quadrupole-sectors configuration allowed the confirmation of the ascribed structure 40 (Scheme 1) <1999PCA3666>. 

It is of interest to mention some detailed mass spectrometric results that were obtained by performing distinct experiments (a) ion-molecule reactions in mixtures of haloben-zenes and ammonia under chemical ionization conditions (b) ion-molecule reactions of mass-selected ionized halobenzenes toward ammonia in a quadrupole collision cell of a hybrid tandem mass spectrometer (c) ion-molecule reactions of phenyl diazonium cations with ammonia in the same quadrupole collision cell and, finally, (d) electrospray ionization of anilines in a hybrid quadrupole-time of flight mass spectrometer (QTof). Characterization of the product ions relies on collisional activation experiments in the low or high kinetic energy regime98. 

So-called hybrid mass spectrometers include a combination of two different types of mass spectrometers in a tandem arrangement. The combination of a magnetic sector mass spectrometer with a quadrupole mass spectrometer was an early instrument of this type. More popular is the combination of a quadrupole for MSI and a TOF for MS2, As with TOF/TOF, these instruments are presently used mainly for proteomics research but could eventually find applications in the clinical lab. These mstruments are unable to perform true precursor ion scans or constant neutral loss scans. Commercial examples of this type of instrument include the qTOF by Waters Micromass and the QSTAR by Apphed Biosystems/MDS Sciex. 

Commercial LITs were introduced in 2002 as either a stand-alone mass spectrometer (LTQ) [318] or as part of a triple quadrupole (Q-Trap) [319] or in 2005 as part of hybrid tandem mass spectrometers (LTQ-Orbitrap and LTQ-FTICR) [88,90], Application of LTQ-FTICR for metabolism studies has been reviewed by Shipkova et al. [90], In comparison to other mass analyzer types, FTICR-based mass spectrometers are not very popular for metabolite identification studies due to availability of less expensive and more user-friendly LTQ-Orbitrap and Q-TOF-based systems. Another limitation associated with the FTICR-based hybrid mass spectrometers is the TOF effect, which results in efficient trapping of only the high-mass ions [90],... 

A triple-quadrupole linear ion trap (QqLIT), which is the most widely used hybrid linear ion trap, is based on the ion path of a triple-quadrupole mass spectrometer with Q3 operated as either a conventional RF/DC quadrupole mass filter or a linear ion trap mass spectrometer. " A QqLIT combines the advantages of a QqQ and a QIT within the same platform without compromising the performance of either mass spectrometer. It retains classical QqQ functions such as MRM, product ion scan, precursor ion scan, and constant neutral loss scan for quantitative and qualitative analysis, and possesses MS" ion accumulation... 

Various hybrid tandem mass spectrometers, which combine two or more distinct types of mass analyzers, have been developed to maximize analytical performance and functionality. From the standpoint of ion/ion reactions, the incorporation of an electrodynamic ion trap into a hybrid instrument allows for the physical separation of the three basic steps involved in an ion/ion reaction experiment, that is, ionization, ion/ion reaction, and mass analysis of reaction products. The separation of these processes provides for the highest degree of flexibility and minimal compromises in the optimization of each step. To date, three major types of hybrid instrnments have been described for ion/ion reaction studies using an electrodynamic ion trap as the reaction vessel. The three major types of hybrid instruments are (i) quadrupole/TOF tandem mass spectrometer (ii) Orbitrap and (iii) LIT /FT-ICR. 

Figure 4.11. Schematic diagram of a quadrupole-orthogonal acceleration time-of-flight hybrid tandem mass spectrometer. (Reproduced from C. Dass, Principles and Practice of Biological Mass Spectrometry, Wiley-Interscience, 2001.)...

An IM-quadMS was the first hybrid instrument used to detect nitrotoluene compounds with a radioactive ionization source [189]. Later work uses laser desorption ionization (LDI) to detect TNT, DNT, RDX, and HMX with an IM-quadMS [190]. Recently, the formation reaction mechanism of RDX response ions in an atmospheric pressure GDI source is now better understood with the use of an IM-triple quadrupole mass spectrometer [179]. 

Glish, G.L. McLuckey, S.A. Ridley, T.Y. Cooks, R.G. A New "Hybrid" Sec-tor/Quadrupole Mass Spectrometer for Mass Spectrometry/Mass Spectrometry. Int. J. Mass Spectrom. Ion Phys. 1982, 41, 157-177. 

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. 

Mass spectrometer configuration. Multianalyzer instruments should be named for the analyzers in the sequence in which they are traversed by the ion beam, where B is a magnetic analyzer, E is an electrostatic analyzer, Q is a quadrupole analyzer, TOP is a time-of-flight analyzer, and ICR is an ion cyclotron resonance analyzer. For example BE mass spectrometer (reversed-geometry double-focusing instrument), BQ mass spectrometer (hybrid sector and quadrupole instrument), EBQ (double-focusing instrument followed by a quadrupole). 

Each type of mass spectrometer has its associated advantages and disadvantages. Quadrupole-based systems offer a fairly simple ion optics design that provides a certain degree of flexibility with respect to instrument configuration. For example, quadrupole mass filters are often found in hybrid systems, that is, coupled with another surface analytical method, such as electron spectroscopy for chemical analysis or scanning Auger spectroscopy. 

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