Tandem mass spectrometry in space

Selected Reaction Monitoring (SRM) Data acquired from specific product ions corresponding to m/z selected precursor ions recorded via two or more stages of mass spectrometry. Selected reaction monitoring can be preformed as tandem mass spectrometry in time or tandem mass spectrometry in space. The term multiple reaction monitoring is deprecated [1],... 

Basically, a tandem mass spectrometer can be conceived in two ways performing tandem mass spectrometry in space by the coupling of two physically distinct instruments, or in time by performing an appropriate sequence of events in an ion storage device. Thus there are two main categories of instruments that allow tandem mass spectrometry experiments tandem mass spectrometers in space or in time. 

Tandem mass spectrometry or MS/MS is frequently used for structural elucidation of phytochemicals to provide more detailed information about the structure and composition of a molecule. This involves two mass spectral steps and fragmentation of the compound occurs between the steps. The two steps may be separated in space or in time depending on whether two distinct separation elements are used (space) or two different separations occur in the same place over time. As described previously, an IT analyzer can be used to successively fragment a molecule to provide MS" spectra, an example of separation in time. A triple quadrupole mass spectrometer is a form of tandem mass spectrometry in space in which two quadrupoles serve as mass filters while a third, positioned in the middle, allows for collision-induced dissociation. Triple quadrupoles are common in phytochemical analysis, and have been used to characterize phenolic compounds in fruit juices (Abad-Garcia et ah, 2009) and procyanidins and alkaloids in cocoa (Ortega et ah, 2010), among others. 

There are two basic instrumental concepts for MS/MS. The first is tandem mass spectrometry in space (or tandem-in-space MS). In order to perform two consecutive mass-analyzing steps, two mass analyzers may be mounted in tandem. Thus, tandem-in-space refers to MS/MS instrumentation where product ion spectra are recorded using spatially separated m/z analyzers. Speedfic m/z separation is performed so that in one section of the instrument ions are selected, then dissociated in an intermediate region, and the products thereof are finally transmitted to a second analyzer for mass analysis (Fig. 9.1). All beam transmitting devices, e.g., multiple sector, ReTOF, TOF/TOF, QqQ, and QqTOF instruments follow this route to tandem MS (Fig. 9.2) [4]. The second approach, tandem mass spectrometry in time (or tandem-in-time MS), enploys a single m/z analyzer (QIT, LIT, FT-ICR) that may be operated by executing the discrete steps of ion selection, activation, and product ion analysis in the very same place but sequentially in time [4]. 

The acquisition and study of the spectra of selected precursor ions, or of precursor ions of a selected neutral mass loss. Structure selective target analyte quantitations use SRM/MRM data acquisition methods. MS/MS can be accomplished using beam instruments incorporating more than one analyser (tandem mass spectrometry in space, triple quadrupole analyzer) or in trap instruments (tandem mass spectrometry in time). 

There are several ways to perform tandem mass spectrometry in an ion trap. Time-dependent rather than space-dependent tandem mass spectrometry occurs in the trap. The general sequence of operations is as follows ... 

Figure 2.14 Tandem mass spectrometry product ion scan experiments in space (a) and in time (b)...

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. 

The deliberate generation of fragments is a valuable tool in structure elucidation and quantification. It is mainly carried out as a second mass analysis after determination of the mass per charge (m/z) ratio of the molecular ions. This approach is called tandem mass spectrometry and it can be carried out either as tandem-in-space using a triple quadrupole (or combinations of... 

Trapping mass spectrometers can also be used as tandem mass spectrometers. Unlike beam-type mstruments, which are referred to as tandem in space, trapping mass spectrometers are tandem in time, meaning that ions are held in one region of space while the parent ion is selected and dissociated and the daughter ion analyzed sequentially in time. The ability to perform tandem mass spectrometry is inherent in the design of trapping mass spectrometers. Gen-... 

Tandem mass spectrometry with events separated (a) in space and (b) in time. (Reprinted (modified) from Ref. 51 with permission of John Wiley Sons)... 

The fundamental process of MS/MS (in a tandem mass spectrometer) is that a particular precursor ion is fragmented (decomposed) into a smaller product ion accompanied by the loss of a neutral fragment. The precursor ion is usually selected in the first analyzer, reacted by some means in a specialized chamber (see below) to produce product ions that are then separated in a second analyzer, hence the terms mass spectrometry/mass spectrometry and tandem mass spectrometry. As discussed later, precmsor and product ion analyses can be separated in space, using sequential analyzers that are either of the same type or in hybrid configurations, or separated in time in the latter the two analytical processes are carried out sequentially, within the same analyzer. There are several MS/MS instrument combinations, including QqQ, QIT, LIT, TOF/TOF, QTOF, LlT-orbitrap, and LIT-FT-ICRMS. 

Tandem mass spectrometry (MS/MS) has attained an enviable status as an analytical tool to identify and quantify compounds in complex mixtures. MS/MS refers to the coupling of two stages of mass analysis, either in time or space. Of all the ionization techniques, only electron ionization (El) provides abundant sttuctural information. To obtain additional structure-specific information by other ionization techniques, it has become essential to perform MS/MS experiments [1,2]. MS/MS was first used in the late 1960s [3]. Since that time, its applications and popularity have continued to grow. Its major contributions are in the fields of structure elucidation of unknown compounds, identification of compounds in complex mixtures, elucidation of fragmentation pathways, and quantification of compounds in real-world samples. In recent times, several new generations of instruments have become available for tandem mass spectrometry applications. Basic concepts of tandem mass spectrometry and an account of these new developments are presented in this chapter. Additional reading material is listed at the end of the chapter. 

The concept of in-space tandem mass spectrometry is illustrated in Figure 4.1. It involves two mass spectrometry systems the first system (MS-1) performs the mass selection of a desired target ion from a stream of ions produced in the ion source. This mass-selected ion undergoes either unimolecular fragmentation [reaction (4.1)] or a chemical reaction in the intermediate region. The second MS... 

Tandem mass spectrometry methods (also abbreviated as MS/MS or MS") are used to characterize individual compounds in mixtures or to determine an individual compound s structure. They are based on the separation of the ions of interest from all other ions, both in space and in time. Separation in space is achieved by coupling two or more mass analyzers, such as BE, EBE, QQ, BEE, etc. Separation in time is achieved using a single mass analyzer (ion trap or ICR), which performs two steps of mass analysis. Once mass separation is completed, various types of experiment can be performed in order to identify the structures of the ions. In a traditional MS/ MS experiment, dissociation products of mass-selected ions are detected. However, different types of experiment, such as the detection of precursor ions for a specific fragment and the identification of ions that have lost a neutral fragment of specific mass, are often available. 

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