Linear Ion-Trap Mass Spectrometers

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. 

Hager, J.W. A New Linear Ion Trap Mass Spectrometer. Rapid Commun. Mass Spectrom. 2002,16, 512-526. 

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. 

Another recent innovation is the QTrap mass spectrometer. The QTrap MS system combines the capabilities of a triple quadrupole mass spectrometer and a linear ion trap mass spectrometer into one MS system. Initially, the QTrap MS was used primarily as a tool for metabolite identification studies [34, 35, 38]. As reported by Li et al. [138], the QTrap MS can also be used as an excellent system for the quantitative analysis of discovery PK samples. The advantage of the QTrap MS system for quantitative analysis is that it can be used to look for plasma metabolites of the NCE and provide an easy way to monitor them while providing the quantitative data on the NCE. 

Hopfgartner, G. Husser, C. Zell, M. Rapid screening and characterization of drug metabolites using a new quadrupole-linear ion trap mass spectrometer. J Mass Spectrom 2003, 38, 138-150. 

Hager, J. W. (2002). A new linear ion trap mass spectrometer. Rapid Commun. Mass Spectrom. 16 512-526. 

Quadrupole, Triple-Quadrupole, and Hybrid Linear Ion Trap Mass Spectrometers for Metabolite Analysis... 

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. 

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. 

Garrett T, Prieto-Conaway M, Kovtoun V, Bui H, Izgarian N, Stafford G, Yost R (2007) Imaging of small molecules in tissue sections with a new intermediate-pressure MALDI linear ion trap mass spectrometer. Int J Mass Spectrom 260 166-176. doi 10.1016/j. ijms.2006.09.019... 

Le Blanc, j. C., Hager, ).W., Ilisiu,A. M., Hunter, C Zhong, F., Chu, I. (2003). Unique scanning capabilities of a new hybrid linear ion trap mass spectrometer (Q TRAP) used for high sensitivity proteomics applications. Proteomics 3, 859-869. 

Marquet, P., Saint-Marcoux, F., Gamble, T.N., Leblanc, J.C. (2003). Comparison of a preliminary procedure for the general unknown screening of drugs and toxic compounds using a quadrupole-linear ion-trap mass spectrometer with a liquid chromatography-mass spectrometry reference technique. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 789(1) 9-18. 

Sanders, M. Josephs, J.L. Wang, J. Phillips, J.J. Mylchreest, 1. Highly Automated Process for the Quantitation of Samples from Animal Pharmacokinetic Studies using a Linear Ion Trap Mass Spectrometer, in Proceedings ofthe 51st ASMS Conference on Mass Spectrometry and Allied Topics, Montreal, Canada, June 8-12, 2003. 

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. 

Yan, Z., Caldwell, G.W., and Maher, N., Unbiased high-throughput screening of reactive metabolites on the linear ion trap mass spectrometer using polarity switch and mass tag triggered data-dependent acquisition, Anal. Chem., 80(16), 6410, 2008. 

Jones, E.B., Quadrupole, triple-quadrupole, and hybrid linear ion trap mass spectrometers for metabolite analysis, in Mass Spectrometry in Drug Metabolism and Pharmacokinetics, Ramanathan, R. (ed.), John Wiley Sons, Hoboken, NJ, 123, 2008. 

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. 

Garrett, T.J. et al., Analysis of intact tissue by intermediate-pressure MALDI on a linear ion trap mass spectrometer, Anal. Chem., 78, 2465, 2006. 

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... 

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