Precursor-ion scanning

A precursor ion scan. Source ions f,. . .., f, ) are all passed successively by Q1 into the collision cell, Q2, where a selected fragment (i ) is produced and detected by Q3. Only the ions (m, f,. fj) give f, fragment ions in this example. 

The ion-trap and Q-ToF instruments are, because of the way that they operate, unable to carry out precursor-ion scans. Computer manipulation of data generated during product-ion scans of the Q-ToF system, however, can yield equivalent data to that produced directly by precursor-ion scans on other instruments and an evaluation of this software-based approach has been carried out [14],... 

The TIC trace from the LC-MS analysis of an extracted river water sample, spiked with 3 p.g dm of atrazine and three of its degradation products, is shown in Figure 3.30. The presence of significant levels of background makes confirmation of the presence of any materials related to atrazine very difficult. The TIC traces from the constant-neutral-loss scan for 42 Da and the precursor-ion scan for m/z 68 are shown in Figure 3.31 and allow the signals from the target compounds to be located readily. 

Precursor-ion scan An MS-MS scan in which those ions that fragment to a given product ion are detected. 

Precursor-ion Scanning Selecting m/z To monitor compounds which in CID give an identical fragment (screening)... 

Precursor ion scan. A product ion is selected by MS2 and a scan by MS, reveals which precursor ions give rise to the selected product ion. 

Orbital trapping mass spectrometers achieve resolutions of up to 105 and would be the next choice after ToF mass spectrometers if resolving powers above 104 are required. In addition to mass resolution, the selectivity of an MS can be critical to distinguish between co-eluting and not mass-resolved compounds. For example, typical triple-quad mass spectrometers usually cannot achieve better than unit-mass resolution. However, special operation modes like neutral loss scans and precursor ion scans can filter out compounds of interest even if neither LC separations nor MS scans would be sufficient to resolve these compounds (note that this is a filtering step). 

A) mass spectrum from negative precursor ion scan of 272 detected the clozapine-GSH adduct at m/z 630 ... 

Lau Y.Y. 2007. High throughput simultaneous detection and identification of reactive intermediates using negative precursor ion scans combined with positive product ion scans. Presented at PittCon 2007. 

In addition to neutral loss scans, mass spectrometers can be used to detect other compounds in a different manner. Acylcamitines are fatty acid esters of carnitine. The masses of acylcamitines differ by the size of the fatty acid attached to it. The tandem mass spectrometer can detect these selectively as well because they all produce a similar product, in this case an ion rather than a molecule. Because it is an ion, it can be detected by the second mass separation device. The ion has a mass of 85 Da and is common to all acylcamitines. Performing a precursor ion scan of 85 Da (essentially a scan of only molecules that produce the 85 ion) reveals a selective analysis of acylcar-nitines, as shown in Fig. 14.2. Additional scans have been added to more selectively detect basic amino acids, free carnitine, short chain acylcamitines and a hormone, thyroxin (T4) which has amino acid components. 

Figure 14.2. Acylcarnitine profile obtained using a precursor ion scan of 85 Da. The profile is from the blood spot of a normal patient.

What are the three most common tandem mass spectrometry (MS/MS) scan modes (product ion scan, precursor ion scan, constant neutral loss scan). 

Tandem mass spectrometry (MS-MS) is a term which covers a number of techniques 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 used 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 number of different MS-MS experiments that can be carried out [9, 10] but the four most widely used are (i) the product-ion scan, (ii) the precursor-ion scan, (iii) the constant-neutral-loss scan, and (iv) selected decomposition monitoring. 

Fig. 2. Schematics of an electrospray triple quadrupole mass spectrometer. A mass spectrum is acquired by scanning the first quadrupole Qi over the desired mass range. For a fragment spectrum the first quadrupole is fixed at a given m/z value transmitting only ions of this m/z value into the gas-filled collision zone. The fragments are extracted and their mass determined by the scanning third quadrupole Q3. For a precursor ion scan the third quadrupole is fixed at the mass of a specific fragment ion (e.g., a phosphate ion) and the second is scanning over the mass range.

Fig. 9. Precursor ion scan on an electrospray triple quadrupole mass spectrometer. From all the peptides present of the digested protein only those that are phosphorylated are detected in a precursor ion scan for the phosphate ion (P03, mass 79 Da) in negative ion mode. From the TPX protein three phosphorylated peptides could be detected Ml, AQLTM PSTPTVLK M2, LSETSVNTEQNSK and M3, VQPVQTTPSKDDVSNSATHVC DVK. M, Oxidized methionine C, carbamidomethylated cysteine.

Whereas TOF instruments solely allow for the detection of product ions of a selected precursor, sector instruments offer additional modes of operation i) to exclusively identify product ions of a particular precursor ion, so-called precursor ion scans, [92,93] or ii) to detect only ions formed by loss of a specific neutral mass, so-called constant neutral loss (CNL) scan. [94] This can be achieved by some technically more demanding linked scans (Table 4.2). [95-98]... 

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