Quadrupole TOF Mass Spectrometers

Recently, Quintela et al. [58] have determined THC and the carboxy metabolite in oral fluid using HPLC coupled to a quadrupole-TOF mass spectrometer. Extreme selectivity of detection and LLOQs of 0.1 and 0.5ng/mL, respectively, were achieved through accurate mass measurement. None of the real positive samples examined was found to contain THC-COOH. 

FIGURE 3A Schematic representation of the chip-CE configuration using a disposable nanoelectrospray emitter interfaced to either a triple quadrupole or a hybrid quadrupole TOF mass spectrometer. Reprinted with permission from [56]. Copyright 2000, The American Chemical Society. 

FIGURE 1.5 Schematic of a modified hybrid quadrupole/TOF mass spectrometer (QSTAR XL) and scan functions in a typical mutual storage mode ion/ion reaction (ions of opposite polarities are generated from a pulsed dual ion source). (Reproduced from Xia, Y. Chrisman, P.A. Erickson, D.E. Liu, J. Liang, X.R. Londry, F.A. Yang, M.J. McLuckey, S.A., Anal. Chem. 2006, 78,4146—4154. With permission from American Chemical Society.)... 

FIGURE 5.3 Schematic of the tandem arrangement of SEADM s P4 parallel plate DMA with MDS/Sciex s Q-Star quadrupole-TOF mass spectrometer. (Courtesy of Dr. C. Hogan.)... 

A major benefit of the oaTOF technology has been the development of hybrid quadrupole/ TOF mass spectrometers. In these instruments a number of RF quadrupole (or other multipole) devices are used to provide the transition from atmospheric pressure sources. 

Figure 2.11. Schematic of a quadrupole time-of-flight (Qq-TOF) mass spectrometer. Reprinted from A. Westman-Brinkmalm and G. Brinkmalm (2002). In Mass Spectrometry and Hyphenated Techniques in Neuropeptide Research. J. Silberring and R. Ekman (eds.) New York John Wiley Sons, 47-105. With permission of John Wiley Sons, Inc.

In a typical analysis, one approach would be to carry out the analysis by first using Cl and quadrupole MS. The fragments from this first MS would then be directed to an El and a TOF mass spectrometer. Different fragments will be observed and this will yield additional information about the sample. In many cases, the MS-MS analysis is applied to samples eluting from either LC, HPLC, or GC chromatographic separation techniques. For additional information on this topic, see Triple Hyphenated Methods. ... 

Perhaps the simplest mass analyzer of all, the TOF mass spectrometer [46] has experienced a reemergence in the past several years. Like the 3D quadrupole ion trap, the TOF analyzer has come to commercial prominence several decades after its initial introduction. The limitations of electronic components in the 1960s constrained the capabilities of the instrument, limiting its mass range and resolving power. The TOF analyzer operates in a pulsed mode, requiring either a pulsed ion... 

The TOF mass analyzer has a low duty cycle, and the combination with an ion accumulation device such as an ion trap is therefore very advantageous. It offers also MS capabilities with accurate mass measurement. In all acquisition modes, the ions are accelerated into the time of flight for mass analysis. Various other hybrid mass spectrometers with TOF have been described, including quadrupole ion trap [70] and linear ion trap [58]. High energy tandem mass spectrometry can be performed on TOF-TOF mass spectrometers [71, 72]. 

A Q-TOF spectrometer is similar to a triple quadrupole but Q3 is replaced by an orthogonal TOF mass spectrometer. Using a Q-TOF instrument only the product ion scan mode can be collected, but because of its high resolving power, accurate masses for both the precursor ion and product ions can be obtained. (See the section below on accurate mass measurements.)... 

ToF mass spectrometers as dynamic instruments gained popularity with the introduction of matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) as effective pulsed ion sources for the soft ionization of large biomolecules (up to 10s dalton) due to their high ion transmission.38 ToF mass spectrometers, quadrupole analyzers and/or magnetic sector fields can be combined in tandem mass spectrometers (MS/MS) for the analysis of organic compounds. 

The axial time-of-flight ICP-MS was introduced in 1998 by LECO (Renaissance, LECO, St. Joseph, MI) and has been commercially available for several years. A schematic of the ICP-ToF-mass spectrometer is shown in Figure 5.11. The analytical performance of this mass spectrometer, which allows 25 000 spectra to be measured per second and is thus faster than a quadrupole ICP-MS,... 

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.)...

Several scan modes are unique to the triple-quadrupole instrument, and most of these modes are superior in duty cycle versus an ion trap, Fourier transform (FT), or time-of-flight (TOF) mass spectrometers. Different elements of the triple-quadrupole perform different operations for each scan mode. These scan modes, each of which will be described in detail, are single-reaction monitoring (SRM) or multiple-reaction monitoring (MRM), precursor ion scanning (PIS), and constant-neutral-loss scanning (NLS). These scan modes and applications for structural elucidation have been described in detail (Yost and Enke, 1978, 1979). 

Similar experiments have previously been performed separately using a triple-quadrupole or an ion trap mass spectrometer for quantitation followed by accurate mass measurements with a Q-TOF mass spectrometer. With the introduction of the LTQ-FTMS instruments, all the data can be gathered quickly and easily with one experimental setup, and the variations in observed metabolic profiles introduced by... 

Superior sensitivity, efficiency, and specificity have made high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the predominant analytical technique for characterization and quantitative analysis of metabolites (Kostiainen et al., 2003 Ma et al., 2006 Prakash et al., 2007). Ion trap, triple-quadrupole, and quadmpole time-of-flight (Q-TOF) mass spectrometers are routinely used to profile and characterize metabolites in plasma and excreta (Ma et al., 2006). The combination of scan types and features available on mass spectrometers of different design (product ion, MS", neutral loss, precursor ion scans, accurate mass measurements) allows identification and characterization of putative and unexpected metabolites with or without little prior knowledge of biotransformation pathways of a given dmg molecule. 

Mass analyzer is the term given to the part of the mass spectrometer that discriminates between ions on the basis of their mass-to-charge ratios (m/z). The most common instruments currently in use with MALDI and ESI sources for the analysis of carbohydrates are quadrupole-based instruments, TOF mass spectrometers, and ion-trapping instruments (ion cyclotron resonance and quadrupole ion-trap designs). 

Among these, both LC-MS and LC-MS/MS approaches have been described using different mass analyzers operating in the positive ion mode scan such as triple stage quadrupole (TSQ) mass spectrometers [145, 194, 226, 227, 235, 239, 240, 242-247] and hybrid quadrupole-linear ion trap (LTQ) [173, 193, 218, 238, 241] mass spectrometers working in SRM mode as well as time-of-flight (TOF) [195] and hybrid quadrupole-TOF (Q-TOF) [236,237] mass spectrometers working in the MS mode. 

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