Tandem-in-space mass

A tandem-in-space mass spectrometer consists of an ion source, a precursor ion activation device, and at least two nontrapping mass analyzers. The first mass analyzer is used to select precursor ions within a narrow m/z range. Isolated precursor ions are allowed to enter the ion activation device, for example, a gas-filled collision cell, where they dissociate. Created fragments continue on to the second mass analyzer for analysis. The second mass analyzer can either acquire a full mass fragment spectrum or be set to monitor a selected, narrow, m/z range. In principle the second mass analyzer could be followed by more ion activation devices and mass analyzers for MSn experiments. However, due to rapidly decreasing transmission and increasing experimental... 

In addition to MRM, the other scan modes available on a QqQ have occasionally been used for residue analysis as well. A precursor ion scan can be used to identify precursor ions from a product ion, and therefore to identify analytes and metabolites or impurities, which generate the same product ion, in complex matrices. For example, erythromycin B was identified in yogurt using this function. In this application, Q3 was held constant to measure a fragment ion at m/z 158, which is a typical product ion of compounds or impurities related to erythromycin A with a desosamine residue. Q1 was then scanned over an appropriate range, from which a precursor ion at m/z 718 was detected. The latter was identified as erythromycin B, which was an impurity in the erythromycin fermentation product. Constant neutral loss scan, which has rare applications for antibiotic analysis, records spectra that show all the precursor ions that have fragmented by the loss of a specific neutral mass. In this instance, both Q1 and Q3 scan together with a constant mass offset between the two quadrupoles. Both precursor ion and constant neutral loss scans can be performed only with ion beam tandem in-space mass spectrometers. 

Discuss the major differences between a tandem-in-space mass spectrometer and a tandem-in-time mass spectrometer. Include the advantages and disadvantages... 

MS-MS in an ion-trap instrument is fundamentally different from MS-MS in sector and triple-quadru-pole instruments. While in the latter the various stages of the process, i.e. precursor ion selection, CID and product-ion mass analysis are performed in different spatial regions of the instrument, in ion-trap instruments these stages are performed consecutively within the ion trap itself. It is tandem-in-time rather than tandem-in-space mass spectrometry. A simplified diagram of an ion-trap system is shown in Figure ID. 

Appropriate use of RF and DC voltages means that some ions can be selectively retained and product ions generated. Some of these ions can then be selected and their product ions generated. In this manner, a fragmentation chain can be established. The ion trap is a typical tandem-in-time mass spectrometer, in which precursor and product ions are created and analysed in the same physical space ionisation and ion analysis, on the other hand, take place at different times ( MS/MS in time )- The operation can be repeated several times, making it possible to perform MS11. Ion trap mass spectrometry thus consists of ... 

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. 

In order to perform two consecutive mass-analyzing steps, two mass analyzers may be mounted in tandem. This technique is applied with beam transmitting devices, i.e., TOF, sector and quadrupole analyzers can be combined that way tandem-in-space, Fig. 4.15). Alternatively, a suitable mass analyzer may be operated by combining selection, activation, and analysis in the very same place. Quad-mpole ion trap (QIT) and ion cyclotron resonance (ICR) instruments can perform such tandem-in-time experiments. 

Boyd, R.K. Linked-Scan Techniques for MS/MS Using Tandem-in-Space Instra-ments. Mass Spectrom. Rev. 1994, 13, 359-410. 

Tandem Mass Spectrometer An instrument capable of performing multiple mass (mjz) analyses. There are two major categories (1) tandem-in-space instruments (triple quadmpole and Q-TOF), (2) tandem-in-time instruments (QIT and FTICR). 

There are two classes of tandem instrument. The original development was CID tandem-in-space MS involving arrangement of two mass analyzers separated by a collision cell. A cartoon of a tandem-in-space instrument is shown in Fig. 10. 

Common tandem-in-space instruments employ a quadrupole as the first mass analyzer, a multipole collision cell (usually hexapole) operated in RF-only mode, and then either a second quadrupole or a TOF tube as the second mass analyzer. These instruments are termed triple or tandem quadrupole and quadrupole-time-of-flight mass spectrometers. 

A third type of MS/MS instruments is a hybrid of tandem-in-space and tandem-in-time devices, including the Q-trap (QQ-2D-linear trap) [45] and the ion trap-FT-ICR (2D-linear ion trap-FT-ICR) [46]. The Q-trap takes the configuration of triple quadrupole, with the third quadrupole replaced by a 2D-linear ion trap. The uniqueness of this design is that the 2D-linear ion trap component can be used to perform either (a) a normal quadrupole scan function in the RF/DC mode or (b) a trap scan function by applying the RF potential to the quadrupole. It is well-suited for both qualitative and quantitative studies. In the case of ion Trap-FT-ICR, it combines ion accumulation and MS" features of a 2D-linear ion trap with excellent mass analysis capability (mass resolution, mass accuracy, and sensitivity) of FT-ICR. 

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-... 

For the beam-type mass analyzers (sector, ToF, and Q), each stage of mass analysis is performed in discrete mass analyzers usually separated by a collision cell. This arrangement is called tandem-in-space. The use of multiple analyzers means that analyzers can be independently selected for the different stages of analysis based on the desired performance characteristics. 

Figure 7 Scan modes for a tandem-in-space instrument, the triple quadruple (QqQ). (a) Full scan all source ions are passed through to Q3 while Q1 and q (collision cell) are set to the RF-only mode, (b) Production scan Qi is set to pass a selected ion (precursor ion). This is fragmented in the collision cell and products are analyzed by scanning Q3. (c) Precursor scan Q1 scans all the source ions into the collision cell for collision-induced dissociation (CID). Q3 is set to pass a selected product ion. A signal recorded at Q3 is correlated with the corresponding precursor ion passing through Q-i. (d) Neutral loss scan Q-i is set to scan ions into the collision cell for CID. The Q3 scan is offset by a specified mass, equal to the mass of the neutral, relative to Qi. (e) Selected reaction monitoring (SRM) an ion selected in Q1 is fragmented and a specific fragment is then recorded after selection by Q3. SRM is commonly used in quantitative work to improve assay selectivity and sensitivity.

The product ion scan entails the mass selection of a precursor ion in the first stage (Qj), fragmentation (CID or ETD) in the collision cell, and then mass analysis of all resultant fragment masses in the second stage of mass analysis (Q3) (Figure 7(b)). This experiment can be performed by beam (tandem-in-space) or trap (tandem-in-time) instruments. It is commonly performed to identify transitions used for quantification by tandem MS or as part of an exercise in structural elucidation. 

In the precursor ion scan, the first mass analyzer (Qj) sequentially scans all precursor ions into the collision cell (Figure 7(c)) for fragmentation. The second analyzer (Qj) is then set to transmit a single specified ion product. The resulting mass spectrum is then a record of all the precursor ions that give rise to the specified common product ion, such as, for example, the metabolites of a particular drug, or class of compounds, which can be fragmented to a common structural moiety. The precursor ion scan can be carried out only with tandem-in-space instruments. 

The types of tandem mass spectrometers capable of performing MS/MS experiments fall into two basic categories tandem in space and tandem in time. Tandem-in-space instruments have discrete mass analyzers for each stage of mass spectrometry examples include multisector, triple-quadru-pole, and hybrid instruments (instruments having mixed types of analyzers such as a magnetic sector and a quadrupole). Tandem-in-time instruments have only one mass analyzer where each stage of mass spectrometry takes place in the same analyzer but is separated in time via a sequence of events. Examples of this type of instrument include Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers and quadrupole ion traps, described in Chapter 3. 

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