Neutral loss scans, mass spectrometry

Figure 5.27 Selective detection of lactolated peptides from a tryptic digest of / -lacto-globulins by LC-electrospray-MS-MS, showing (a) the total-ion-cnrrent trace in full-scan mode, and (b) the total-ion-current trace in neutral-loss-scanning mode. Figure from Selective detection of lactolated peptides in hydrolysates by liquid chromatography/ electrospray tandem mass spectrometry , by Molle, D., Morgan, F., BouhaUab, S. and Leonil, J., in Analytical Biochemistry, Volume 259, 152-161, Copyright 1998, Elsevier Science (USA), reproduced with permission from the publisher.

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. 

Another technological development in tandem mass spectrometry is the combination of two TOP mass spectrometers, TOF/TOK These instruments have excellent sensitivity and throughput for MALDI-MS/MS and are especially suited for proteomics research. However, these instruments are unable to perform true precursor ion scans or constant neutral loss scans. The Bruker Daltonics ultra-flex and Applied Biosystem 4700 proteomics analyzer are examples of this type of instrument, Such mstruments have yet to make an impact in clinical chemistry. 

The most popular two-dimensional mass spectrometry configuration at present is the QQQ, or triple-sector quadrupole, represented schematically in Fig. 3.9. Three scan modes are possible with this configuration product ion scan, precursor ion scan, and constant neutral loss scan. Product ion scan is the most widely used, and involves using Qj to selectively transmit one precursor ion to Q2 where it is fragmented, normally by collisions with an inert gas such as helium. This type of fragmentation is referred to as collision-induced dissociation, or CID. Q2 is operated in radio frequency mode only, and thus stores ions of a broad m/z range until they are transmitted to Q3 for mass analysis of the product ions. 

Lafaye A, Junot C, Ramounet-Le Gall B, Fritsch P, Ezan E, Tabet JC. Profiling of sulfoconjugates in urine by using precursor ion and neutral loss scans in tandem mass spectrometry. Application to the investigation of heavy metal toxicity in rats. / Mass Spectrom. 2004 39(6) 655-664. 

Williams, T.T.J. Perreault, H. Selective Detection of Nitrated Polycyclic Aromatic Hydrocarbons by Electrospray Ionization Mass Spectrometry and Constant Neutral Loss Scanning. Rapid Common. Mass Spectrom. 2000, 14. 1474-1481. 

Fig. 11.16. Representation of three tandem mass spectrometry (MS/MS) scan modes illustrated for a triple quadrupole instrument configuration. The top panel shows the attributes of the popular and prevalent product ion CID experiment. The first mass filter is held at a constant m/z value transmitting only ions of a single mlz value into the collision region. Conversion of a portion of translational energy into internal energy in the collision event results in excitation of the mass-selected ions, followed by unimolecular dissociation. The spectrum of product ions is recorded by scanning the second mass filter (commonly referred to as Q3 ). The center panel illustrates the precursor ion CID experiment. Ions of all mlz values are transmitted sequentially into the collision region as the first analyzer (Ql) is scanned. Only dissociation processes that generate product ions of a specific mlz ratio are transmitted by Q3 to the detector. The lower panel shows the constant neutral loss CID experiment. Both mass analyzers are scanned simultaneously, at the same rate, and at a constant mlz offset. The mlz offset is selected on the basis of known neutral elimination products (e.g., H20, NH3, CH3COOH, etc.) that may be particularly diagnostic of one or more compound classes that may be present in a sample mixture. The utility of the two compound class-specific scans (precursor ion and neutral loss) is illustrated in Fig. 11.17.

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