Instrumentation tandem mass spectrometer

For some complex mixtures, the combination of LC and MS does not provide enough resolution. In recent years it has become feasible to couple two or more mass analyzers to form tandem mass spectrometers (see Section 20C--S). When combined with LC, the tandem mass spectrometry system is called an LC/MS/MS instrument. Tandem mass spectrometers are usually triple quadrupole systems or quadrupole ion-trap spectrometers. To attain higher resolution than can be achieved with a quadrupole, the final mass analyzer in a tandem MS system can be a time-of-flight mass spectrometer. Sector mass spectrometers can also be combined to give tandem systems. Ion cyclotron resonance and ion-trap... 

Magnetic sectors can be used on their own, or in conjunction with energy analysers to fomi a tandem mass spectrometer. The unique features of the reverse geometry instrument are presented from this point. 

Aside from the smgle mass filter, the most connnon configuration for quadnipole mass spectrometers is the triple-quadnipole instrument. This is the simplest tandem mass spectrometer using quadnipole mass filters. Typically, the... 

Tandem mass spectrometer with an HPLC pump, pre-column (Phenomex CN Bester, AJO-4304), column (LC-CN Supelco 58979), autosampler and data-hand-ling system. Standard instrumentation such as the Micromass micro (Waters, Milford MA, USA) has sufficient sensitivity. 

These are not the only types of tandem mass spectrometers. There are numerous configurations of instruments that are based on the type of ion separation and many new terms associated with these instrument types. For example, there are instruments known as ion traps. The ion trap is a device that can measure mass, fragment a selected mass (as could be done in a collision cell) and then measure the mass of the fragment. The product ion produced by this all in one device is the same product ion that would be produced in a tandem quadrupole instrument. However, there is only one mass analyzer that functions as both the collision cell and mass measuring device. These types of instruments are sometimes referred to as tandem mass spectrometers, but are not abbreviated as MS/MS. The MS/MS analysis is done by separating the analysis in time (tandem in time) rather than two devices separated in space. A more generic term is best suited. This term is MS , where the n represents... 

Fig. 8.1.1 Simple illustrations of a various mass spectrometers, a The triple-quadrupole tandem mass spectrometer (top panel). The middle set of quadrupoles are part of the collision cell (CC) and do not perform mass separation. MSI and MS2 indicate the first and second quadrupole mass separation devices, respectively. The bold arrow shows the path of ions, b Ion-trap mass spectrometer (middle left). The charged sections of the ion trap are not elliptical as drawn, but rather hyperbolic. The diagram is also two-dimensional, whereas the ion trap is three-dimensional. The ion path is such that ions enter the device and are trapped until a specific voltage ejects these ions, c Time of Flight mass spectrometer with a Reflectron (middle left). Ions are separated by the time it takes to pass through the instrument. The Reflectron improves/focuses the ions, d Hybrid Tandem mass spectrometer (bottom). The diagram shows that a quadrupole instrument can be combined with a different type of mass spectrometer, forming a tandem hybrid instrument...

Finally, it is important to note there are many other instruments and configurations that are often referred to as tandem mass spectrometers. There are hybrid instruments that use another form of mass separation, time-of-flight (TOF) mass spectrometry. TOF mass spectrometry separates ions based on the time it takes to... 

ToF mass spectrometers as dynamic instruments gained popularity with the introduction of matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) as effective pulsed ion sources for the soft ionization of large biomolecules (up to 10s dalton) due to their high ion transmission.38 ToF mass spectrometers, quadrupole analyzers and/or magnetic sector fields can be combined in tandem mass spectrometers (MS/MS) for the analysis of organic compounds. 

Instruments that incorporate two or three mass analysers in a series have been developed to study ion fragmentation. Several of the same type of mass analyser can constitute a tandem mass spectrometer, or they can be constructed using different mass analysers (hybrids). Hybrid spectrometers include the combination of magnetic sector followed by quadrupole, multiple quadrupole, quadrupole TOF, etc. In these instruments, a collision cell is placed between each analyser (Fig. 16.23). Tandem instruments have different scanning modes. 

The most common types of MS/MS instruments available to researchers in food chemistry include triple quadrupole mass spectrometers and ion traps. Less common but commercially produced tandem mass spectrometers include magnetic sector instruments, Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, and quadrupole time-of-flight (QTOF) hybrid instruments (Table A.3A.1). Beginning in 2001, TOF-TOF tandem mass spectrometers became available from instrument manufacturers. These instruments have the potential to deliver high-resolution tandem mass spectra with high speed and should be compatible with the chip-based chromatography systems now under development. 

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). 

Hybrid Mass Spectrometer A tandem mass spectrometer comprised of multiple mass analyzers of different types. A Q-TOF is a hybrid, but a triple quadmpole is not. Ideally, a hybrid instrument harnesses the best features of each mass analyzer type to produce a system perhaps greater than the sum of the parts. 

A critical review of the inherent limitations of modern PFA analytical methods is available in Martin et al. [18], but some examples are discussed here. For quantitative determination, the HPLC system is often interfaced to a Micromass or Sciex tandem mass spectrometer operated in the negative ion electrospray mode. Instrumental parameters are optimized to transmit the [M - H] ion for all analytes (Table 5). When possible, multiple daughter ions are monitored, but quantitation is generally based on a single product ion (Table 5, Fig. 4). In the electrospray tandem mass spectrometry (ES MS/MS) system, the 499 Da -> 80 Da transition can provide a stronger signal than... 

A few years ago, we began a research program to develop methods of analysis which would involve the use of FAB and a high performance tandem mass spectrometer. The tandem instrument was the first triple sector mass spectrometer to be designed and built by a commercial instrument company (Kratos of Manchester, U.K.). The first mass spectrometer of the combination is a double focussing Kratos MS-50 which is coupled to a low resolution electrostatic analyzer, which serves as the second mass spectrometer U). This FAB MS-MS combination has been used to verify the structures of an unknown cyclic peptide (2), a new amino acid modified by diphtheria toxin (3), and an ornithine-containing lipid (4). A number of methods have also been worked out which rely on this instrumentation. They Include the structural determination of cyclic peptides (5), nucleosides and nucleotides (6), and unsaturated fatty acids (7) and the analysis of mixtures of both anionic (8) and cationic surfactants (9). 

For the detection, a tandem mass spectrometer Quattro Micro API ESCI (Waters Corp., Milford, MA) with a triple quadrupole was employed. The instrument was operated in electrospray in the positive ionization mode (ESI+) with the following optimized parameters capillary voltage, 0.5 kV source block temperature, 130 °C nebulization and desolvation gas (nitrogen) heated at 400 °C and delivered at 800 L/h, and as cone gas at 50 L/h collision cell pressure, 3 x 1(F6 bar (argon). Data was recorded in the multiple reaction monitoring (MRM) mode by selection of the two most intense precursor-to-product ion transitions for each analyte, except for the ISs, for which only one transition was monitored. The most intense transition for each analyte was used for quantitative purposes. Table 2 shows MRM transitions, cone voltages and collision energies used for the analysis of the antidepressants included in the LC-MS/MS method. 

One way to carry out MS-MS is to link two or more mass analyzers in series to produce an instrument capable of selecting a single ion, and examining how that ion (either a parent or daughter ion) fragments. For instance, three quadrupoles can be linked (a so called triple quad ) to produce a tandem mass spectrometer. In this arrangement, the first quadrupole selects a specific ion for further analysis, the second... 

In order for an instrument to carry out MS-MS, it must be able to do the three operations outlined above. As we have seen however, ion-trap systems capable of MS-MS and MS(n) do not use a tandem arrangement of mass analyzers at all, but rather use a single ion trap for all three operations simultaneously. As has already been stated, these ion-trap tandem mass spectrometer experiments are very sensitive and are now user friendly. The ion trap brings the capability for carrying out MS-MS experiments to the benchtop at relatively low cost. 

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