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Ion Trap Mass Spectrometry

The ion trap is a device that utilizes ion path stability of ions for separating them by their m/z [53]. The quadrupole ion trap and the related quadrupole mass filter were invented by Paul and Steinwedel [57]. A quadrupole ion trap (QITor 3D-IT) mass spectrometer operates with a three-dimensional quadrupole field. The QIT is formed by three electrodes: a ring electrode with a donut shape placed symmetrically between two end cap electrodes (Fig. 1.20).

By applying a fundamental RF potential, the QIT can be described as a small ion storage device where ions are focused toward the center of the trap by collision with helium gas. In the QIT, because of the cylindrical symmetry of the trap, the x and y components of the field are combined to a single radial r component, where r2 = x2 + y2. The motion of ions in the trap is characterized by one radial and one axial frequency (secular frequencies). Like quadrupoles, the motion of ions can be described by the solutions of Matthieu's equations (a, q). Ions with various m/z can be stored in the trap with the condition that trajectories are stable in r- and z- directions. Each ion of a certain m/z will be trapped at a certain qz value. The higher m/z ions will be located at lower q values while the lower m/z will be located at the higher qz values. The quadrupole ion trap can store only a limited number of ions before space charging occurs. To circumvent this effect, most instruments have an automatic gain control procedure (AGC). This procedure exactly determines the adequate fill time of the trap to maximize sensitivity and minimize resolution losses due to space charge. A mass spectrum can be obtained by mass-selective ejection where the amplitude of the RF potential is continuously increased at a certain rate. Ions with the lowest m/z are ejected first. The mass-selective axial instability mode requires that the ions are confined at the center of the trap and at a limited mass range. Resonant mass ejection is another procedure which can generate a mass spectrum with a higher mass range. Ion motion can be modified either by exciting the radial or the axial frequencies by applying a small oscillating potential at the end cap electrodes during the RF ramp. In both mass-analyzing modes, the resolution of the spectrum is strongly dependent on the speed at which the RF amplitude is increased. Higher resolution can be obtained with slower scan speed. Compared to quadru-pole instruments with the quadrupole ion trap, high sensitivity can be obtained in full-scan mode due to the ability of ion accumulation in the trap before mass analysis. Rapid mass analysis with the mass instability scan allows scanning at a speed of several thousand m/z units per second. There are several important components which affect the time necessary to obtain a mass spectrum (duty cycle): (i) the injection time (within 0.5-500.0 ms), (ii) the scan speed (in the range 5000-20 000 m/z units s-1), (iii) isolation of the precursor ion and fragmentation in tandem MS or MSn. Contrarily to the triple quadrupole, MS/MS is not performed in space but in time. Another significant difference is the use of helium as collision gas. Because the trap is permanently filled with gas, the instrument can switch very rapidly from single MS to MS/MS mode. High sensitivity can be achieved in the QIT because of ion selective accumulation of the precursor. Another advantage compared to the triple quadrupole is the short duty cycle for an MS/MS experiment. A typical MSn (MS3) sequence is illustrated in Fig. 1.21. To obtain a MS 2 spectrum the precursor ion is isolated and then excited while fragments are trapped. The next step to obtain an MS3 spectrum is to isolate a fragment ion again and to perform CID fragmentation. Because MS/MS is performed in time in the same physical device, the operation can be repeated several times. Most commercial instruments can perform MSn to the tenth or 11th level. A difficulty is to excite the precursor ions efficiently and trap the product ions in the same device. Generally, solely the precursor is excited in a specific window corresponding to 1-4 m/z units. The consequence is that fragment ions are not further excited and cannot produce second generation fragments. In many cases,

Fig. 1.21 Typical MS3 scheme m/z 552 ! m/z 202 !. In a first step the protonated bosentan molecule at m/z 552 is isolated and fragmented (MS2). The fragments are trapped. In a second step the fragment at m/z 202 is isolated and fragmented and the spectrum is recorded.
Fig. 1.22 Various MS2 and MS3 spectra of bosentan: (A) MS2, (B) MS3, (C) MS3, (D) MS3. F1 to F4 correspond to the main fragments of bosentan obtained also on the QqQ.

MS2 trap CID generates similar spectra than quadrupole CID, but there are cases where the spectra differ significantly.

For molecules which can easily lose water or ammonia, the most abundant fragment observed in MS2 is M-18 or M-17, which is not very informative. To overcome this limitation, wide band excitation (range 20 m/z units) can be applied. Another difference compared to QqQ is that QIT have a low mass cutoff of about one-third of the mass of the precursor ion. However QIT is particularly attractive to follow fragmentation cascades as illustrated for bosentan in Fig. 1.22. It can clearly be concluded that the fragment at m/z 175 originated from the precursor at 202 and not from the precursor at m/z 311.

Due to the high sensitivity in MSn mode, ion traps are particular attractive for qualitative analysis in drug metabolism and proteomics studies. Compared to QqQ, similar sensitivities can be achieved for quantitative analysis but at the cost of precision and accuracy. A major difference is the number of transitions which can be monitored at the same time. While more than 100 SRM transitions can be recorded within one second on a QqQ, this number is much lower with the QIT (generally four to eight transitions). Ion traps have larger mass ranges (up to 50 000) than quadrupole instruments but smaller ranges than time of flight mass analyzers. Most commercial instruments use two mass ranges: (i) from m/z 50 to m/z 2000-3000 with a mass resolution of 0.7 m/z units or better and (ii) from m/z 200 to m/z 4000-6000 with a mass resolution of 2-4 m/z units.

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Front Section

Fig. 1.23 Standalone linear ion trap. Because the ions are ejected radially two detectors are required for best sensitivity. Adapted with permission from reference [59].

Back Section

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