Tandem mass spectrometry scan modes

Main processes in tandem mass spectrometry (MS/MS). CID stands for collision-induced dissociation, as occurs when an inert gas is present in the collision cell. 

Note that precursor or neutral loss scans are not possible in time separation analysers. 

The product ion scan is the only one available directly with these mass spectrometers. 

However, with these instruments, the process can be easily repeated over several ion 

Symbolism proposed by Cooks et al. for the easy representation of various scan modes. 

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Welti, R., Wang, X. and Williams, T.D. (2003) Electrospray ionization tandem mass spectrometry scan modes for plant chloroplast lipids. Anal. Biochem. 314, 149-152. 

Figure 5.27 Selective detection of lactolated peptides from a tryptic digest of / -lacto-globulins by LC-electrospray-MS-MS, showing (a) the total-ion-cnrrent trace in full-scan mode, and (b) the total-ion-current trace in neutral-loss-scanning mode. Figure from Selective detection of lactolated peptides in hydrolysates by liquid chromatography/ electrospray tandem mass spectrometry , by Molle, D., Morgan, F., BouhaUab, S. and Leonil, J., in Analytical Biochemistry, Volume 259, 152-161, Copyright 1998, Elsevier Science (USA), reproduced with permission from the publisher.

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. 

TOF analyzers are especially compatible with MALDI ion sources and hence are frequently coupled in aMALDI-TOF configuration. Nevertheless, many commercial mass spectrometers combine ESI with TOF with great success. For proteomics applications, the quadrupole TOF (QqTOF) hybrid instruments with their superior mass accuracy, mass range, and mass resolution are of much greater utility than simple TOF instruments.21,22 Moreover, TOF instruments feature high sensitivity because they can generate full scan data without the necessity for scanning that causes ion loss and decreased sensitivity. Linear mode TOF instruments cannot perform tandem mass spectrometry. This problem is addressed by hybrid instruments that incorporate analyzers with mass selective capability (e.g., QqTOF) in front of a TOF instrument. 

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.

What are the three most common tandem mass spectrometry (MS/MS) scan modes (product ion scan, precursor ion scan, constant neutral loss scan). 

Tandem mass spectrometry, more commonly known as MS-MS, utilises multiple stages of analysis. It is very selective and provides useful structural information. A variety of scan modes can be used to provide specific information for structural... 

Fig. 5 Statistical evaluation of LC-MS-based methods for tropane alkaloids referred in this chapter. (a) Relative frequency of ionization methods. +APCI positive atmospheric pressure chemical ionization, +ESI positive electrospray ionization, FAB fast atom bombardment, +TSP positive thermospray, (b) Relative frequency of scan modes used. MS full scan MS, MS/MS tandem mass spectrometry (product ion scan), MRM multiple reaction monitoring, SIM selected ion monitoring, (c) Relative frequency of mass analysers used. EBQtQ2 double focusing sector field mass spectrometer, IT ion trap, QqQ triple quadrupole, SQ single quadrupole. Considered publications were found by PubMed data-based search and references cited in these articles...

The four main scan modes available using tandem mass spectrometry are represented in Figure 4.3. Many other MS/MS scan modes are possible. We will focus on fragmentations that occur with an inert collision gas. MS/MS needs a computer system able to control all the experimental factors and to record the results. 

The three-dimensional quadupole field ion trap - or Paul trap is a three-electrode device [see Figure 4.5(b)]. Ions are injected into the device and collected in packets from an ESI or MALDI source. The ion trap analyzer is capable of MS, MS" (MS = MS-MS-MS) and high-resolution scans (R = 20,000). The ion packets enter through an entrance-end cap and are analyzed by scanning the RF amplitude of the ring electrode. The ions are resonated sequentially from low to high m/z and are ejected from the ion trap through the exit-end cap electrode to a detector. Unlike the triple quadrupole (QqQ) mass spectrometer discussed previously, the ion trap performs tandem mass spectrometry (MS-MS) scan modes in the same analyzer. 

The various scan modes of the mass spectrometer provide powerful methods of analysis and unique capabilities for information gathering [54,55], For example, the full scan mode is used to survey the ions that are generated in the source to confirm or identify structure based on molecular weight assignment. The resulting full scan mass spectrum, therefore, contains an ion(s) that is indicative of molecular weight. Two dimensions of mass analysis or tandem mass spectrometry (MS/MS) provide powerful capabilities for qualitative and quantitative analysis. For example,... 

Practical applications of tandem mass spectrometry reqnire data to be acquired in the following fonr scan modes. A pictorial representation of these scans and their symbolism is given in Figure 4.2. 

Figure 8 (A) Schematic representation of the four scan modes used in tandem mass spectrometry. (B) Kondrat symbolism, where a filled circle indicates a fixed mass analyzer and an open circle indicates a scanning analyzer.

Triple quadrupole instruments (Section 6.4.3) have not previously been considered suitable for use with MALDl sources in view of their nature as scanning analyzers (serial recording of a mass spectrum resulting in very low duty cycle in full spectral acquisitions) with a limited miz range. However, for the present purpose of small molecule quantitation by MALDl, neither of these limitations applies. In particular, if the so-called multiple reaction monitoring (MRM) mode of tandem mass spectrometry is... 

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