Constant mass difference scans

A constant-mass-difference scan. Source ions (m, f,. .., fj) are passed successively by Q1 into Q2, where collisionally induced dissociation occurs. Q3 is set to pass only those ions produced in Q2 that have a predetermined mass difference (Am) between the ions passed by Ql. In this example, they are m, - f, (= Am) and f, - fj (= Am), so, although all ions pass into Q2, only f, f, have a mass difference (Am) equal to that selected for Q3. 

Neutral-loss scan The first and third quadrupoles are linked and scanned at the same speed over the same mass range with a constant mass difference between the two analyzers. Because of the mass offset at any time quadrupole 3 will transmit product ions (if any) with a fixed lower m/z value than the mass selected precursor ions transmitted by quadrupole 1. The result is a mass spectrum containing all the precursor ions that loose a neutral species of selected mass. 

Figure 6 Acquisition modes in tandem MS with two mass anaiyzers. Muitipie arrows indicate a fuii scan, a singie arrow a singie ion scan (mass fiiter fixed on a singie m/z). in the neutral loss scan, a full scan with a constant mass difference is performed with both anaiyzers, selecting only ions which show a neutral loss. (Graphic adapted from Ref. 23.)...

Tandem mass spectrometry (MS-MS) is a term which covers a number of techniqnes in which one stage of mass spectrometry, not necessarily the first, is used to isolate an ion of interest and a second stage is then nsed to probe the relationship of this ion with others from which it may have been generated or which it may generate on decomposition. The two stages of mass spectrometry are related in specific ways in order to provide the desired analytical information. There are a large nnmber of different MS-MS experiments that can be carried ont [9, 10] bnt the fonr most widely nsed are (i) the prodnct-ion scan, (ii) the precnrsor-ion scan, (iii) the constant-nentral-loss scan, and (iv) selected decomposition monitoring. 

Several scan modes are unique to the triple-quadrupole instrument, and most of these modes are superior in duty cycle versus an ion trap, Fourier transform (FT), or time-of-flight (TOF) mass spectrometers. Different elements of the triple-quadrupole perform different operations for each scan mode. These scan modes, each of which will be described in detail, are single-reaction monitoring (SRM) or multiple-reaction monitoring (MRM), precursor ion scanning (PIS), and constant-neutral-loss scanning (NLS). These scan modes and applications for structural elucidation have been described in detail (Yost and Enke, 1978, 1979). 

Figure 3.6. Schematic of constant neutral loss scan (NLS). Q1 and Q3 scan through a defined mass range, but Q3 is set to scan a fixed mass difference below Q1. Only compounds that generate the specified neutral will hit the detector and register a signal.

In the third common scan mode, both mass spectrometers are scanned together, but with a constant mass offset between the two. Thus, for a mass difference a, when an ion of mass m goes through the first mass spectrometer, detection occurs if this ion has yielded a fragment ion of mass (m — a) when it leaves the collision cell. This is a neutral loss scan , the neutral having the mass a. For example, in chemical ionization the alcohol molecular ion loses a water molecule. Alcohols are thus detected by scanning a neutral loss of 18 mass units. On the other hand, a given mass increase can be detected if a reactive gas is introduced within the collision cell. 

If the scan is carried out while respecting the condition deriving from this equation, the fragment ion formed between the source and the analyser is passed on by the two sectors only if it differs by a constant mass m from its precursor. 

So-called hybrid mass spectrometers include a combination of two different types of mass spectrometers in a tandem arrangement. The combination of a magnetic sector mass spectrometer with a quadrupole mass spectrometer was an early instrument of this type. More popular is the combination of a quadrupole for MSI and a TOF for MS2, As with TOF/TOF, these instruments are presently used mainly for proteomics research but could eventually find applications in the clinical lab. These mstruments are unable to perform true precursor ion scans or constant neutral loss scans. Commercial examples of this type of instrument include the qTOF by Waters Micromass and the QSTAR by Apphed Biosystems/MDS Sciex. 

Another tandem screening method is known as constant neutral loss scanning. Here, both mass spectrometers are scanned simultaneously but are offset corresponding to the difference between precursor and product ion masses. A signal only appears when a precursor ion yields a product ion with the mass difference selected. This technique can be used to screen for compounds that contain a specific structural feature that yields a common fragmentation process. 

Quadrupole mass filters can be scanned across the secondary ion m/q range by adjusting the RF and DC components together. Two modes of operation are available. One allows for the transmission of secondary ions of different m/q ratio with a constant mass resolution m/ 4m as discussed in Section 5.1.1.1.1). This, however, results in a decrease in transmission with increasing mass (scales approximately as m Q. The other mode allows for constant transmission but with a variable mass resolution with mass. Qwing to the greater ambiguity introduced, the constant mass resolution mode is typically applied when these mass filters are used in SIMS. 

Such mass filters do, however, display many attributes relative to other mass filters. As an example, they do not discard signals of different m/q ratio as is done in other m/q scanning-based mass filters such as the Quadrupole and Magnetic Sector mass filters. In addition, the transmission function of these mass filters does not decrease with increasing m/q when operated in constant mass resolution mode as does in Quadrupole mass filters. And lastly, these mass filters are relatively small units compared to all but the Ion Cyclotron Resonance mass filter (commercial units range from 10 to 25 cm). 

In neutral loss scan, all precursor ions, which lose a particular neutral particle (that otherwise cannot be detected in MS), are detected. Both mass analysers scan, but with a constant selected mass difference, which corresponds to the mass of the neutral particle lost. This analysis technique is particularly meaningful if molecules contain the same functional groups (e.g., metabolites as acids, glucuronides or sulfates). In this way, it is possible to identify the starting ions which are characterized by the loss of a common structural element. Both MS/MS scan techniques can be used for substance-class-specific detection in triple quadrupole systems. Ion trap systems allow the mapping of these processes by linking the scans between separate stages of MS in time. 

A scan procedure for a tandem mass spectrometer designed to monitor a selected neutral loss mass difference from precursor ions by detection of the corresponding product ions produced by metastable ion fragmentation or collision-induced dissociation. Synonymous terms are constant neutral mass loss scan and fixed neutral fragment... 

The techniques referred to above (Sects. 1—3) may be operated for a sample heated in a constant temperature environment or under conditions of programmed temperature change. Very similar equipment can often be used differences normally reside in the temperature control of the reactant cell. Non-isothermal measurements of mass loss are termed thermogravimetry (TG), absorption or evolution of heat is differential scanning calorimetry (DSC), and measurement of the temperature difference between the sample and an inert reference substance is termed differential thermal analysis (DTA). These techniques can be used singly [33,76,174] or in combination and may include provision for EGA. Applications of non-isothermal measurements have ranged from the rapid qualitative estimation of reaction temperature to the quantitative determination of kinetic parameters [175—177]. The evaluation of kinetic parameters from non-isothermal data is dealt with in detail in Chap. 3.6. 

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