Neutral loss scan mode

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.

S. Kazuno, M. Yanagida, N. Shindo and K. Murayama, Mass spectrometric identification and quantification of glycosyl flavonoids, including dihydrochalcones with neutral loss scan mode, Anal. Biochem., 347, 182 192 (2005). 

A product ion scan can obtain stmctural information of a given precursor ion while a precursor ion scan is more suited to find stmctural homologues in a complex mixture. Bosentan (Mr = 551, Fig. 1.19) has two metabolites corresponding to the tert-butyl hydroxylation product (Mr = 567) and the dealkylation of the me-thoxy group to form the phenol (Mr = 537). Bosentan (Tracker, Actelion Phrama-ceuticals) is an oral duel endothelin receptor antagonist approved for the use in arterial hypertension [56]. Selection of the fragment at m/z 280 can fish out precursor ions corresponding only to bosentan and these two metabolites (Fig. 1.19C). A similar result is obtained with the constant-neutral loss scan mode (Fig. 1.19D) which is based on neutral loss of 44 units. 

Different MS MS experiments of product ion scan, precursor ion scan, and neutral loss scan modes of selected flavonoids can be carried out in order to confirm the structure of flavonoids previously detected by the full-scan mode. In the product ion scan experiments, MS MS product ions can be produced by CID of selected precursor ions in the collision cell of the triple-quadrupole mass spectrometer (Q2) and mass analyzed using the second analyzer of the instrument (Q3). However, in the precursor ion scan experiments, Q1 scans over all possible precursors of the selected ion in Q3 of the triple quadrupole. Finally, in neutral loss... 

Carr et al., 1993). The neutral loss scan mode is used as a class identifier to also screen components that contain a common substructure. Barbuch et al. demonstrated this approach for the class identification of phytoestrogens (Barbuch et al., 1989), using thermospray ionization (TSI)-LC/MS/MS. Brownsill et al. used a similar electrospray ionization (ESI)-LC/MS/MS approach for the analysis of metabolites in rat liver slices (Brownsill et al., 1994). 

Neutral loss scan mode involves introducing a fixed mass offset to Qj and Q3. Qj and Q3 are scanned in tandem, maintaining... 

Figure 2.7 Schematic diagram of tandem mass spectrometric techniques. CID denotes collision-indnced dissociation. The and x= I, 2, 3,. ..) stand for molecular (or precursor) and product ions, respectively. The letter a in the neutral-loss scan mode denotes the mass of the neutral-loss fragment.

The elimination of stable neutral particles is a common fragmentation reaction. These include HgO, CO, COg, NO, HCN, HCl, RCOOH and alkenes (McLafferty, 1959). These reactions can usually be recognized from the corresponding ions and mass differences in the spectra. Eliminations are particularly likely to occur when a-cleavage is impossible. MS/MS mass spectrometer providing the neutral loss scan mode allow a substance class-specific detection based on the elimination of neutrals. 

In addition to the product-ion scan, most MS-MS instruments allow other scan modes, e.g. neutral-loss and precursor-ion scan modes. The modes are not only useful in the elucidation of the fragmentation pattern of a particular compound, but also in the screening for a series of structurally-related compounds in complex samples. In the product-ion scan mode, the first mass analyser selects a particular precursor ion, while the product ions obtained by CID of this precursor are analysed in the second mass analyser. In the precursor-ion scan mode, this process is virtually reversed the first mass analyser transmits all ions in a preset mIz window to the collision cell, while the second analyser selects only the ions of one particular miz, e.g. a particular structure informative fragment for a series of ions or compounds. An example of the use of the precursor-ion scan mode is the monitoring of phthalate plasticisers by means of the common fragment ion at miz 149 due to protonated phthalic anhydride. In the neutral-loss scan modes, both mass analysers are... 

Similar screening procedures may be applied to perform Phase II metabolic profiling, i.e. based on the neutral-loss scan mode with a loss of 176 or 80 Da for glucuronide and sulfate conjugates, respectively. 

For the analytical use of MS/MS, other scan modes can be useful as well as the product-ion scan mode. The various modes are explained and summarized in Table 1. The precursor-ion and neutral-loss scan modes are particularly useful in screening. They are part of a powerful analytical strategy applicable in impurity, degradation product and/or metabolite profiling, as well as other applications where searching for structurally related compounds is important. After an appropriate ionization mode is found, a product-ion mass spectrum is obtained for the parent compound. In this spectrum, possible common precursor ions and/or common neutral losses have to be identified. 

---