Triple Quadrupole Linear Ion Trap

In a linear ion trap one of the most efficient ways to perform mass analysis is to eject ions radially. Hager [60] demonstrated that, by using fringe field effects, ions can also be mass-selectively ejected in the axial direction. There are several benefits for axial ejection (i) it does not require open slits in the quadrupole, (ii) the device can be operated either as a regular quadrupole or a LIT using one detector. A commercial hybrid mass spectrometer was developed based on a triple quadrupole platform where Q3 can be operated either in normal RF/DC mode or in the LIT ion trap mode (Fig. 1.24). 

With quadrupole CID all fragments are recorded in one experiment, while in the case of the 3D ion trap MS, MS and experiments are required to ob- 

The major advantage of this instrument is that qualitative and quantitative analysis can be performed in the same LC-MS run. As an example in a data-dependent experiment, the selected reaction monitoring mode can be used as a survey scan and the enhanced product ion mode (EPI) as a dependent scan. The consequence is that for each quantified analyte a confirmatory MS/MS spectmm can be obtained. 

Product ion scan (PIS) Resolving (fixed) Fragment Resolving (scan) 

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Mass spectrometric analysis was performed with a hybrid triple quadrupole/ linear ion trap Applied Biosystem MSD Sciex 4000QTRAP (Applied Biosystems, Foster City, USA) instrument equipped with a Turbospray ESI interface. For target quantitative analyses, data acquisition was performed in SRM, recording the transitions between the precursor ion and the two most abundant fragment ions. The developed instrumental method display excellent LODs in SRM mode between 0.5 and 1.2 pg (Table 2). 

QqLIT Triple quadrupole-linear ion trap mass analyzer... 

Fig. 1.24 Schematic of the triple quadrupole linear ion trap (AB/MDS Sciex). Q3 can be operated in quadrupole or trap mode. In both modes ions are detected in the axial direction.

In the triple quadrupole linear ion trap, tandem MS is performed in space where the LIT serves only as a trapping and mass-analyzing device. Figure 1.25 illustrates the difference between quadrupole CID spectra and trap CID spectra for trocade. 

Table 1.4 Mode of operation of the triple quadrupole linear ion trap (QqQLir).

Fig. 1.39 LC-MS data dependent analysis of vinpocetin in rat urine using dynamic background substraction (DBS) on a triple quadrupole linear ion trap. (A) Full scan MS (survey scan) trace. (B) Enhanced product ion scan (dependent scan). The major peak at 3.9 min corresponds to apovinpocetin, the minor one at 2.9 min to the hydroxylation product of apovinpocetin (m/z 339).

Hopfgartner, G. Varesio, E. Tschappat, V. Grivet, C. Emmanuel Bourgogne, E. Leuthold, L. A. Triple quadrupole linear ion trap mass spectrometer for the analysis of small molecules and macromolecules. J. Mass Spectrom. 2004, 39, 845-855. 

Since the analytical point of view most of current analytical methods are based on LC-MS/MS, but for some classes of pesticides GC-MS continues being the technique of choice. The use of quadrupole ion trap (QIT) to analyze multiple pesticide residues is limited to several multiclass pesticides in fruit [162], because of the limited number of ions that can be isolated at the same time. For this reason, the use of several time windows is required and this is indeed a strong limitation in practice. The use of hybrid triple quadrupole linear ion trap (QqLlT) mass spectrometer has provided significant contribution to the development of high-sensitive multiresidue analytical methods for pesticide control. An example of application is the method reported by Hernando et al. for the analysis of pesticide residues in olive oil [65]. 

A new generation of linear ion trap mass spectrometers has been developed and exhibits increased performance compared to traditional three-dimensional (3D) ion traps (Hopfgartner et al., 2003 Douglas et al., 2005). A further evolution of the triple-quadrupole family and ion trap class of instruments is the production of the hybrid triple-quadrupole/linear ion trap (QQQ/LIT) platform. Hybrid instruments of this nature allow for operation in space and not just in time when performing MS/MS analysis. This feature allows for increased performance compared to classical ion traps. A powerful combination possible on a hybrid LIT/QQQ instrument is the ability to use highly sensitive and selective precursor ion, constant neutral loss, and multi-MRM as a survey scan for dependent LIT MS/MS. Compared to a simple MS experiment, these comprehensive triple-quadrupole and LIT modes can be more complex to setup. 

Li, A. C., Gohdes, M. A., and Shou, W. Z. (2007). N-in-one strategy for metabolite identification using a liquid chromatography/hybrid triple quadrupole linear ion trap instrument using multiple dependent product ion scans triggered with full mass scan. Rapid Commun. Mass Spectrom. 21 1421-1430. 

Zhang, M. Y., Pace, N., Kerns, E. H., Kleintop, T., Kagan, N., and Sakuma, T. (2005). Hybrid triple quadrupole-linear ion trap mass spectrometry in fragmentation mechanism studies Application to structure elucidation of buspirone and one of its metabolites. J. Mass. Spectrom. 40 1017-1029. 

Williamson, B. L., Marchese, J., and Morrice, N. A. (2006). Automated identification and quantification of protein phosphorylation sites by LC/MS on a hybrid triple quadrupole linear ion trap mass spectrometer. Mol. Cell. Proteomics 5 337-346. 

Thomas, A., Hopfgartner, G., Giroud, C., and Staub, C. (2009). Quantitative and qualitative profiling of endocannabinoids in human plasma using a triple quadrupole linear ion trap mass spectrometer with liquid chromatography. Rapid Commun. Mass Spectrom. 23, 629—638. 

Shou, W.Z. et al., A novel approach to perform metabolite screening during the quantitative LC-MS/MS analyses of in vitro metabolic stability samples using a hybrid triple-quadrupole linear ion trap mass spectrometer, J. Mass Spectrom., 40(10), 1347, 2005. 

S uzuki et al. report a hybrid triple quadrupole/linear ion trap MS/MS technique. The triple quad-rupole-linear ion trap LC/MS combines the scan speed and sensitivity of ion trap MS while retaining the selective scanning modes of triple quadrupole MS. The ability to perform both types of MS on a single instrument reduces the time required for analysis while eliminating the chance of errors due to analyzing different samples in multiple MS runs. The method, coupled with LC separation, was demonstrated to be usefuUy applied to the structure elucidation of YTX analogues. ... 

Sierra Analytics and Applied Biosystems investigated the metabolic profile of indinavir, an HIV protease inhibitor with a very short half-life (2 hours), readily metabolised via CYPs to produce phase I and subsequent II products. Aliquots (10 pL) of indinavir incubated with rat liver S9 fractions were separated by online liquid chromatography and analysed with an Applied Biosystems hybrid triple quadrupole/linear ion trap mass spectrometer in information dependent acquisition (IDA) mode. This consisted of an enhanced MS survey scan followed by enhanced product ion scans for the two most intense parent ions as dependent MS/MS experiments. 

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... 

Since this original description of the ETD/CID MS/MS scan type (ETcaD), it has been implemented on commercial instruments, applied toward biologically-relevant samples, and expanded upon [28,85,91,92]. For example, Han et al. [92] coupled ETD with beam-type CID on their QTRAP hybrid triple quadrupole/linear ion trap instrument (Figure 3.4). An advantage of both this implementation, and beam-type CID in general, is that the spectra do not suffer from the low mass cut-off that is... 

FIGURE 3.4 Schematic diagram of the QTRAP hybrid triple quadrupole/linear ion trap instrument that has been modified to conduct ion/ion reactions in Q2. (Reproduced from Han, H.L. Xia, Y. McLuckey, S.A., Rapid Commun. Mass Spectrom. 2007, 21, 1567-1573. With permission from John Wiley Sons, Inc.)... 

Yao M, Ma L, Duchoslav E, Zhu M. Rapid screening and characterization of drug metabolites using multiple ion monitoring dependent product ion scan and postacquisition data mining on a hybrid triple quadrupole-linear ion trap mass spectrometer. Rapid Commun Mass Spectrom 2009 23(11) 1683 1693. 

FIGURE 8.15 Schematic of triple quadrupole linear ion trap. Q3 can be operated either with RF/dc as a standard quadrupole or with RF as linear ion trap with axial... 

TABLE 8.5 Mode of Operation of Triple Quadrupole Linear Ion Trap (QqQux)... 

Hopfgartner G, Varesio E, Stoeckli M. Matrix-assisted laser desorption/ionization mass spectrometric imaging of complete rat sections using a triple quadrupole linear ion trap. Rapid Commtm Mass Spectrom 2009 23(6) 733—736. 

Mauriala T, Chauret N, Oballa R, Nicoll-Griffith DA, Bateman KP. A strategy for identification of drug metabolites from dried blood spots using triple-quadrupole/ linear ion trap hybrid mass spectrometry. Rapid Commun Mass Spectrom 2005 19 1984-1992. 

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