Tandem mass spectrometry triple quadrupole

Johnson, J. Yost, R. Kelley, P. Bradford, D. (1990). Tandem-In-Space and Tandem-In-Time Mass Spectrometry Triple Quadrupoles and Quadrupole Ion Traps. Amd. Chem. Vol.62, N°20, pp. 2162-2172, ISSN 0003-2700. 

Figure 10.4 Evolution of chemical ionization products of diethyl ethylphosphonate using methane as reagent gas [19]. Reprinted with permission from Johnson, j.V, Yost, R.A., Kelley, RE., Bradford, D.C. (1990) Tandem-in-space and Tandem-in-time Mass-spectrometry - Triple Quadrupoles and Quadrupole Ion Traps. Anal. Chem. 62 2162-2172. Copyright (1990) American Chemical Society...

Johnson JV, Yost RA, Kelley PE, Bradford DC. Tandem-in-space and tandem-in-time mass spectrometry triple quadrupoles and quadrupole ion traps. Anal Chem. 1990 62 2162-72. 

Tandem mass spectrometry (MS/MS) is a method for obtaining sequence and structural information by measurement of the mass-to-charge ratios of ionized molecules before and after dissociation reactions within a mass spectrometer which consists essentially of two mass spectrometers in tandem. In the first step, precursor ions are selected for further fragmentation by energy impact and interaction with a collision gas. The generated product ions can be analyzed by a second scan step. MS/MS measurements of peptides can be performed using electrospray or matrix-assisted laser desorption/ionization in combination with triple quadruple, ion trap, quadrupole-TOF (time-of-flight), TOF-TOF or ion cyclotron resonance MS. Tandem... 

Figure 5.40 Product-ion spectrum of the (M + H)+ ion (m/z 614) of Indinavir with the proposed origins of the ions observed. Reprinted by permission of Elsevier Science from Identification of in vitro metabolites of Indinavir by Intelligent Automated LC-MS/MS (INTAMS) utilizing triple-quadrupole tandem mass spectrometry , by Yu, X., Cui, D. and Davis, M. R., Journal of the American Society for Mass Spectrometry, Vol. 10, pp. 175-183, Copyright 1999 by the American Society for Mass Spectrometry.

Tandem mass spectrometry (MS-MS) uses more than one mass analyzer for structural and sequencing studies that have been found very useful for anthocyanin characterization. These mass analyzers may be of the same type (triple or quadru-poie)85,86 Qj. such as ion trap quadrupole, - and quadrupole-time-of-flight... 

A further extension of the DFG S19 method was achieved when polar analytes and those unsuitable for GC were determined by LC/MS or more preferably by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Triple-quadrupole MS/MS and ion trap MS" have become more affordable and acceptable in the recent past. These techniques provide multiple analyte methods by employing modes such as time segments, scan events or multiple injections. By improving the selectivity and sensitivity of detection after HPLC separation, the DFG S19 extraction and cleanup scheme can be applied to polar or high molecular weight analytes, and cleanup steps such as Si02 fractionation or even GPC become unnecessary. 

Different mass analysers can be combined with the electrospray ionization source to effect analysis. These include magnetic sector analysers, quadrupole filter (Q), quadrupole ion trap (QIT), time of flight (TOF), and more recently the Fourrier transform ion cyclotron resonance (FTICR) mass analysers. Tandem mass spectrometry can also be effected by combining one or more mass analysers in tandem, as in a triple quadrupole or a QTOF. The first analyzer is usually used as a mass filter to select parent ions that can be fragmented and analyzed by subsequent analysers. 

Figeys, D. Aebersold, R. High sensitivity identification of proteins by electrospray ionization tandem mass spectrometry inital comparison between an ion trap mass spectrometer and a triple quadrupole mass spectrometer. Electrophoresis 1997,18, 360-368. 

Figure 3.9 Conceptual view of tandem mass spectrometry with a tandem-inspace triple quadrupole mass analyzer." The first mass analyzer (Ql) selects the precursor ion of interest by allowing only it to pass, while discriminating against all others. The precursor ion is then fragmented, usually by energetic collisions, in the second quadrupole (q2) that is operated in transmissive mode allowing all fragment ions to be collimated and passed into the third quadrupole (Q3). Q3 performs mass analysis on the product ions that compose the tandem mass spectra and are rationalized to a structure.

Multiple mass analyzers exist that can perform tandem mass spectrometry. Some use a tandem-in-space configuration, such as the triple quadrupole mass analyzers illustrated (Fig.3.9). Others use a tandem-in-time configuration and include instruments such as ion-traps (ITMS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS or FTMS). A triple quadrupole mass spectrometer can only perform the tandem process once for an isolated precursor ion (e.g., MS/MS), but trapping or tandem-in-time instruments can perform repetitive tandem mass spectrometry (MS ), thus adding n 1 degrees of structural characterization and elucidation. When an ion-trap is combined with HPLC and photodiode array detection, the net result is a profiling tool that is a powerful tool for both metabolite profiling and metabolite identification. 

Fig. 11.16. Representation of three tandem mass spectrometry (MS/MS) scan modes illustrated for a triple quadrupole instrument configuration. The top panel shows the attributes of the popular and prevalent product ion CID experiment. The first mass filter is held at a constant m/z value transmitting only ions of a single mlz value into the collision region. Conversion of a portion of translational energy into internal energy in the collision event results in excitation of the mass-selected ions, followed by unimolecular dissociation. The spectrum of product ions is recorded by scanning the second mass filter (commonly referred to as Q3 ). The center panel illustrates the precursor ion CID experiment. Ions of all mlz values are transmitted sequentially into the collision region as the first analyzer (Ql) is scanned. Only dissociation processes that generate product ions of a specific mlz ratio are transmitted by Q3 to the detector. The lower panel shows the constant neutral loss CID experiment. Both mass analyzers are scanned simultaneously, at the same rate, and at a constant mlz offset. The mlz offset is selected on the basis of known neutral elimination products (e.g., H20, NH3, CH3COOH, etc.) that may be particularly diagnostic of one or more compound classes that may be present in a sample mixture. The utility of the two compound class-specific scans (precursor ion and neutral loss) is illustrated in Fig. 11.17.

Fig. 7. Protein identification with electrospray tandem mass spectrometry and a triple quadrupole mass spectrometer. Fragment spectra of several peptides are generated during one investigation. From the fragment spectra short sequence stretches can be read. Together with their mass location in the peptide of the measured mass, they can be used to specifically identify a protein in the database. Because the protein identification depends only on one peptide, several proteins can be identified from one sample.

Fig. 1.6 (A) Electron impact spectrum obtained on a single quadrupole mass spectrometer of a compound with Mr = 355. (B) Product ion spectrum after atmospheric pressure ionization obtained on a triple quadrupole instrument. Chemical ionization and atmospheric pressure ionization give in both cases protonated precursor ions, which is ideal for tandem mass spectrometry.

A triple quadrupole instrument (QqQ) is a combination of two mass quadrupole mass filters (tandem mass spectrometry) separated by a collision cell which is also a quadrupole operating in RE-only mode (Pig. 1.18). A common nomencla-... 

Jemal, M. Ouyang, Z. Enhanced resolution triple-quadrupole mass spectrometry for fast quantitative bioanalysis using liquid chromatography/tandem mass spectrometry investigations of parameters that affect ruggedness. Rapid Commun Mass Spectrom 2003, 17, 24-38. 

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