Parent ion selection

Schwartz, J.C. Jardine, I. High-Resolution Parent-Ion Selection/-Isolation Using a QIT Mass Spectrometer. Rapid Commun. Mass Spectrom. 1992,6,313-317. 

Instrnments combining several analyzers in sequential order are very common. This combination allows mass spectrometry and mass spectrometry experiments (MS/MS) to be carried out. Modern MS/MS includes many different experiments designed to generate substructural information or to qnantitate componnds at trace levels. A triple quadru-pole mass spectrometer allows one to obtain a daughter ion mass spec-trnm resnlting from the decomposition of a parent ion selected in the first qnadrnpole. The MS/MS experiments using an FTICR or ion trap, however, are carried ont in a time-resolved manner rather than by spatial resolntion. 

MS/MS. The capability of trapping ions for long periods of time is one of the most interesting features of FTMS, and it is this capability that has made FTMS (and its precursor, ion cyclotron resonance) the method of choice for ion-molecule reaction studies. It is this capability that has also lead to the development of MS/MS techniques for FTMS [11]. FTMS has demonstrated capabilities for high resolution daughter ion detection [42-44], and consecutive MS/MS reactions [45], that have shown it to be an intriguing alternative to the use of the instruments with multiple analysis stages. Initial concerns about limited resolution for parent ion selection have been allayed by the development of a stored waveform, inverse Fourier transform method of excitation by Marshall and coworkers [9,10] which allows the operator to tailor the excitation waveform to the desired experiment. 

We have recently shown that it is possible to perform MS/MS experiments by making use of the ion-electron collisions in a Fourier transform mass spectrometer [54], Parent ion selection, which could not easily be achieved in the previous experiments, is accomplished by gating off the electron beam for a short period of... 

To exploit the advantages of FTMS fully we have implemented several predefined ejection, activation and acceleration options, like single shots, covers, sweeps over some mass window, sweeps around some unaccelerated mass window, tickling belts with phase inversion, parent ion selection chirps, activation shots for daughter ion production, etc. 

J. C. Schwartz and I. Jardine, High-resolution parent-ion selection/isolation using a quadrupole ion-trap mass spectrometer. Rapid Commun. Mass Spectrom. 6, 313-317 (1992). 

MRM is characterized by parent ion selection in Qj, fragmentation in Q2, and key fragment isolation in Qj. The resultant trace can be integrated in a quantitative manner. 

A very nice example of the power of Mossbauer spectroscopy was the demonstration [37] of site selective doping of compound 111-V semiconductors such as GaAs, where it was concluded from the measured Sn isomer shift that implanted In and Sb radioactive parent ions selectively populate 111 and V sites respectively. 

A number of low-molecular-weight A-acyl amino acid lipids of biological significance were identified based on values of t and miz values provided by IMS-MS. Both data acquisition and visnalization of the separated isomeric lipids is rapidly achieved. For example, A-arachidonoyl isoleucine, and A-arachidonoyl leucine exhibit t fingerprints that are sufficiently distinct to delineate isomeric composition. It is often difficult to obtain meaningful MS/MS fragment ions from these low abundant lipids for structural characterization. The mass window for parent ion selection for most MS instruments is insufficient to cleanly select isobaric compounds, and the fragmentation pattern of isomers is commonly very similar. 

The most common modes of operation for ms/ms systems include daughter scan, parent ion scan, neutral loss scan, and selected reaction monitoring. The mode chosen depends on the information required. Stmctural identification is generally obtained using daughter or parent ion scan. The mass analyzers commonly used in tandem systems include quadmpole, magnetic-sector, electric-sector, time-of-flight, and ion cyclotron resonance. Some instmments add a third analyzer such as the triple quadmpole ms (27). 

This selected ion monitoring (SIM) approach typically has greater applicability in cases where sensitivity is more of a concern. Kiehl and Kennington developed a swine liver confirmatory method for tilmicosin that confirmed structure based upon monitoring a parent ion and two additional structural fragment ions. A discussion of the validation requirements for confirmatory methods is provided in Section 6. 

Different mass analysers can be combined with the electrospray ionization source to effect analysis. These include magnetic sector analysers, quadrupole filter (Q), quadrupole ion trap (QIT), time of flight (TOF), and more recently the Fourrier transform ion cyclotron resonance (FTICR) mass analysers. Tandem mass spectrometry can also be effected by combining one or more mass analysers in tandem, as in a triple quadrupole or a QTOF. The first analyzer is usually used as a mass filter to select parent ions that can be fragmented and analyzed by subsequent analysers. 

Figure 2. (a) Reflection TOF mass spectrometer, (b) Depicts the electrostatic potentials. With a judicious selection of potential, the daughter ions arising from metastable decay arrive at the detector prior to the parent ions which have higher kinetic energy. MCP denotes a microchannel plate charged particle detector, (a) Taken with permission from ref. 22 (b) Taken with permission from ref. 19. 

Once formed, the metal coenzymes are more easily selected by proteins than the parent ions due to the idiosyncratic nature of each ring. 

Microprobe laser desorption laser ionisation mass spectrometry (/xL2MS) is used to provide spatial resolution and identification of organic molecules across a meteorite sample. Tracking the chemical composition across the surface of the meteorite requires a full mass spectrum to be measured every 10 p,m across the surface. The molecules must be desorbed from the surface with minimal disruption to their chemical structure to prevent fragmentation so that the mass spectrum consists principally of parent ions. Ideally, the conventional electron bombardment ionisation technique can be replaced with an ionisation that is selective to the carbonaceous species of interest to simplify the mass spectrum. Most information will be obtained if small samples are used so that sensitivity levels should be lower than attomolar (10—18 M) fewer than 1000 molecules can be detected and above all it must be certain that the molecules came from the sample and are not introduced by the instrument itself. 

The LC/MS/MS method utilizes the principle of three-dimensional separation to achieve excellent selectivity based on chromatographic separation (reversed-phase, size-exclusive, ionic, etc.), the unique mass-to-charge ratio of the analyte s parent ion, and the fragment ion. A sample clean up... 

To select between these two alternative structures it was necessary to synthesize a labeled analog. Three hydrogen atoms of the methyl moiety of the ester group were substituted for deuterium. One of the principal pathways of fragmentation of [M N2]+ ions involves the loss of CH3 radical. Since all R substitutes in diazo ketones 4-1 were also methyls it was important to detect what group exactly is eliminated from the [M N2]+ ion. The spectrum of deuterated sample has confirmed that the methyl radical of the ester moiety leaves the parent ion. As a result the cyclic structure 4-2 was selected as the most probable. The ketene structure 4-3 is hardly able to trigger this process, while for heterocyclic ion 4-2 it is highly favorable (Scheme 5.22). 

Figure 6.3. Real-life example of a tandem MS experiment in an electrospray ion trap instrument. Top panel a complex peptide mixture. Middle panel ion at 1318.9 m/z was isolated from other sample components. Note the lack of any other peaks and a very low background. Bottom panel fragmentation spectrum of the selected parent ion (1318.9 m/z), note the different scale of the m/z axis. All peaks seen in this mass spectrum are product ions that were formed due to the controlled fragmentation of the parent ion. The main peak at 1300.8 m/z corresponds to the loss of water molecule, a lower intensity parent ion at 1318.9 m/z is also seen.

To be able to use MS/MS spectra library searching for general unknown screening, it is necessary to use an automatic process, called data dependent acquisition or information-dependent acquisition, to select the parent ions of interest, totally unexpected by definition, and to dissociate them and monitor their fragments. 

The soft API techniques such as APCI and ESI, which are predominantly applied nowadays fulfil the most desirable criteria for an ionisation method in MS-MS, especially for mixture analysis, where each compound contained in the mixture produce as few—ideally only one—ions of different mass-to-charge ratio (m/z) as possible upon ionisation. The result would be a quite simple FIA-MS overview spectrum with few interferences in the parent ion to be selected... 

These results obtained from the analyses of industrial blends proved that the identification of the constituents of the different surfactant blends in the FIA-MS and MS-MS mode can be performed successfully in a time-saving manner only using the product ion scan carried out in mixture analysis mode. The applicability of positive ionisation either using FIA-MS for screening and MS-MS for the identification of these surfactants was evaluated after the blends examined before were mixed resulting in a complex surfactant mixture (cf. Fig. 2.5.7(a)). Identification of selected mixture constituents known to belong to the different blends used for mixture composition was performed by applying the whole spectrum of analytical techniques provided by MS-MS such as product ion, parent ion and/or neutral loss scans. 

First a screening in the APCI—FIA—MS(+) and APCI—FIA—MS(—) mode was carried out. From the positively generated overview spectrum as presented in Fig. 2.5.7(a) for identification, characteristic parent ions already known from the FIA—MS spectra of the pure blends and examined by MS—MS now were selected for MS—MS examination of the mixture. From the composed surfactant mixture, the ions at m/z 380, 556 and 670 were submitted to CID in positive APCI—FIA—MS—MS mode. Product ion spectra of these ions are presented in Fig. 2.5.7(b)—(d). 

Fig. 2.5.7. (a) APCI-FIA-MS(+) screening recording an artificial formulation mixed from surfactant blends as presented in Figs. 2.5.3 (AES), 2.5.5 (AE) and 2.5.6 (polyglycol amine blend). Product ion spectra of selected parent ions m/z 380, 556 and 670 of surfactant formulation as in (a) obtained by APCI-FIA-MS-MS(+). 

An improved specificity was observed when FIA-MS-MS in product or parent ion mode was used to perform quantification of the surfactants in the methanolic mixtures. The ions selected for quantitation in product or parent ion mode were C13-AE m/z 71, 85, 99, 113, and 127 from alkyl chain together with 89, 133, and 177 from PEG chain generated from parent ions m/z 394, 526, 658, 790 and 922 alkylbenzyl dimethyl ammonium quat m/z 91 and 58 generated from parent ion m/z 214 FADA m/z 88, 106 and 227 generated from parent ions m/z 232, 260, 288, 316, 344 and 372 while the alkylamido betaine was quantified generating the parent ion m/z 343 obtained from product ion at m/z 240. 

Fig. 2.6.10. APCI-FIA-MS-MS(+) (CID) daughter ion mass spectrum of selected [M + NH4]+ parent ion (mjz 340) of potential carboxylated non-ionic surfactant metabolite of precursor NPEO prepared by chemical synthesis structure of short-chain NPEC CgHi9-C6H4-0-(CH2-CH2-0)-CH2-C00H fragmentation behaviour under CID presented in the inset [28],... 

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