Selected-ion-monitoring

The current trend in SIM technique is toward computer control of the mass spectrometer with concurrent software development allowing data reduction as peak areas and channel ratios. TTie process of manually distinguishing several ion profiles and of making measurements from an 

It is important to place these recent developments in perspective since the vast majority of laboratories obtain satisfactory data by hand . However, where there is a heavy commitment to routine assay or a special need for high precision, some degree of automation with computer involvement should be considered. 

Element Atomic mass (amu) Natural abundance (atom %) 

Measurement by stable isotope dilution was introduced for quantitative SIM using a deuterated methoxime derivative of prostaglandin Ei 

Sensitivity. When operated in an ion monitoring mode as a GC detector, a mass spectrometer with standard electron multiplier detection and signal amplification is theoretically capable of producing a response to samples of less than 10 mol (1 femtomole) [68]. In practice such limits have not been reached due to the combined effects of variable stationary phase and instrument background, sample degradation in gas chromatography or, in isotope dilution, residual blank contributions from 

The operation of mass spectrometers in the repetitive scanning mode is useful for the identification of the components of a mixture. If quantitation is a major issue (below), selected ion monitoring (SIM) is preferably employed the term multiple ion detection (MID) and some others are also in use [37]. In the SIM mode, the mass analyzer is operated in a way that it alternately acquires only the ionic masses of interest, i.e., it junps from one m/z to the next [38-43]. The informa- 

As the monitored m/z values are selected to best represent the target compound, SIM exhibits good selectivity that can be further increased by high-resolution SIM (HR-SIM) because HR-SIM almost eliminates isobaric interferences [45-48]. To ensure precise and drift-free positioning on narrow peaks, HR-SIM requires one or several lock masses to be enployed although those are rarely explicitly mentioned in the literature [48,49]. The role of the lock mass is to serve as internal mass reference for accurate mass measurement. (For examples cf. Chap. 14.2.) 

Only scanning instruments like magnetic sector and (triple) quadrupole mass spectrometers show inproved sensitivity in SIM mode. Quadrupole ion traps (QIT and LIT) might be operated as to deliver a SIM output, the time to achieve ion selection is, however, essentially identical to their full scan cycle time, thus cancel- 

Note Normally, three to ten m/z values are monitored 20-100 ms each in one SIM cycle. Some settling time is needed for the mass analyzer after switching to the next value, e.g., 1-2 ms for pure electric scanning, 20-50 ms for a magnet scan. Due to the comparatively slow axial ion velocity in (triple) quadrupole instruments, the time to empty the quadrupole from one ionic species prior to setting it to the next has to be taken into account. 

The operation of magnetic sector (Chap. 4.3), linear quadrupole (Chap. 4.4), or quadrupole ion trap (Chap. 4.5) mass spectrometers in the repetitive scanning mode is useful for the identification of the components of a mixture. If quantitation is a major issue (below), selected ion monitoring (SIM) is preferably employed the term multiple ion detection (MID) and some others are also in use. [33] In the SIM mode, the mass analyzer is operated in a way that it alternately acquires only the ionic masses of interest, i.e. it jumps from one m/z value to the next. [34-39] The information obtained from a SIM trace is equivalent to that from a RIC, but no mass spectra are recorded. Thus, the scan time spent on a diagnostically useless m/z range is almost reduced to zero, whereas the detector time for the ions of interest is increased by a factor of 10-100. [40] An analogous improvement in sensitivity (Chap. 5.2.3) is also observed. 

Any ionization method exhibits compound-dependent ionization efficiencies (Chap. 2.4). Whether a specific compound is rather preferred or suppressed relative to another greatly depends on the ionization process employed. This makes a careful calibration of the instrument s response versus the sample concentration become prerequisite for reliable quantitation. [6,7] 

External standardization is obtained by constructing a calibration curve, i.e., from plotting measured intensities versus rising concentration of the target compound. Calibration curves are generally linear over a wide range of concentrations. When concentration approaches the detection limit (Chap. 5.2.3) the graph deviates from 

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In a process similar to that described in the previous item, the stored data can be used to identify not just a series of compounds but specific ones. For example, any compound containing a chlorine atom is obvious from its mass spectrum, since natural chlorine occurs as two isotopes, Cl and Cl, in a ratio of. 3 1. Thus its mass spectrum will have two molecular ions separated by two mass units (35 -i- 2 = 37) in an abundance ratio of 3 1. It becomes a trivial exercise for the computer to print out only those scans in which two ions are found separated by two mass units in the abundance ratio of 3 1 (Figure 36.10). This selection of only certain ion masses is called selected ion recording (SIR) or, sometimes, selected ion monitoring (SIM, an unfortunate... 

Selected-ion monitoring (SIM). Describes the operation of a mass spectrometer in which the ion currents at one (or several) selected m/z values are recorded, rather than the entire mass spectrum. The use of the terms multiple-ion detection (MID), multiple-ion (peak) monitoring (MPM), and mass fragmentography are not recommended. 

Quantitative mass spectrometry, also used for pharmaceutical appHcations, involves the use of isotopicaHy labeled internal standards for method calibration and the calculation of percent recoveries (9). Maximum sensitivity is obtained when the mass spectrometer is set to monitor only a few ions, which are characteristic of the target compounds to be quantified, a procedure known as the selected ion monitoring mode (sim). When chlorinated species are to be detected, then two ions from the isotopic envelope can be monitored, and confirmation of the target compound can be based not only on the gc retention time and the mass, but on the ratio of the two ion abundances being close to the theoretically expected value. The spectrometer cycles through the ions in the shortest possible time. This avoids compromising the chromatographic resolution of the gc, because even after extraction the sample contains many compounds in addition to the analyte. To increase sensitivity, some methods use sample concentration techniques. 

Solid-phase microextraction (SPME) was used for headspace sampling. The FFA were extracted from the headspace with PA, Car/PDMS, and CW/DVB fibers. It was examined whether addition of salt (NaCl) and decreasing the pH by addition of sulphuric acid (H SO ) increased the sensitivity. FFA were analyzed using gas chromatography coupled to mass spectrometry in selected ion monitoring. 

This set-up, or a very similar one, has been used to determine different group of pollutants in environmental waters (45, 83, 93). For example, with 10 ml of sample the limits of detection of a group of pesticides were between 2 and 20 ng 1 (92) in tap and river water, with this system being fully automated. Figure 13.19 shows the chromatograms obtained by on-line SPE-GC-MS under selected ion-monitoring conditions of 10 ml of tap water spiked with pesticides at levels of 0.1 pig 1 (92). 

Figure 15.8 Multidimensional GC-MS separation of urinary acids after derivatization with methyl chloroformate (a) pre-column cliromatogram after splitless injection (h) Main-column selected ion monitoring cliromatogram (mass 84) of pyroglutamic acid methyl ester. Adapted from Journal of Chromatography, B 714, M. Heil et ai, Enantioselective multidimensional gas chromatography-mass spectrometry in the analysis of urinary organic acids , pp. 119-126, copyright 1998, with permission from Elsevier Science.

Selected ion monitoring of mass 127 is used to determine the concentration of formaldehyde. 

Approximate retention time (min) Amino acid For selected ion monitoring... 

Watson, J. T., Hubbard, W. C., Sweetman, B. J., and Pelster, D. R. Quantitative analysis of prostaglandins by selected ion monitoring GC/MS. Advan. in Mass Spectr. in Biochern. Med II. New York Spectrum Publications, 1976. 

Retention times and suggested ions for selected ion monitoring (SIM) of TBDMS derivatives of AAs are given in Table 9.1 and the GC separation is shown in Figure 9.1. Amino acids should be derivatized prior to separation. The TBDMS derivatives are preferred and stable for at least 1 week. 

Table 9.3. Selected ion monitoring of some PTH-AAs as the TBDMS derivatives...

Selected ion monitoring (SIM) Describes the operation of a MS in which the ion currents of one or several selected m/z values are recorded, rather than the entire mass spectrum. 

The Use of Selected-Ion Monitoring to Examine the Number of Terminal Galactose Moieties on a Glycoprotein 143... 

Like the UV detector, the mass spectrometer may be employed as either a general detector, when full-scan mass spectra are acquired, or as a specific detector, when selected-ion monitoring (see Section 3.5.2.1) or tandem mass spectrometry (MS-MS) (see Section 3.4.2) are being used. 

In conventional mass spectromefiy, quantitative determinations are often carried out by using selected-ion monitoring (SIM), i.e. by monitoring the intensities of a small number of ions characteristic of the analyte of interest (see Section 3.5.2.1 below). 

What are the potential advantages of selected-decomposition monitoring (SDM) over selected-ion monitoring (SIM) ... 

The great advantage of SDM over SIM is that it usually confers even greater selectivity onto the analysis and reduces the amount of chemical noise observed. Selected-ion monitoring is concerned with particular... 

In this chapter, the main aspects of mass spectrometry that are necessary for the application of LC-MS have been described. In particular, the use of selected-ion monitoring (SIM) for the development of sensitive and specific assays, and the use of MS-MS for generating structural information from species generated by soft ionization techniques, have been highlighted. Some important aspects of both qualitative and quantitative data analysis have been described and the power of using mass profiles to enhance selectivity and sensitivity has been demonstrated. 

To understand the circumstances in which particular features of mass spectrometry, such as high-resolution measurements, MS-MS and cone-voltage fragmentation, selected-ion monitoring and selected-decomposition monitoring, may be nsed to address particular analytical problems. 

What is selected-ion monitoring and what are the advantages of using this techniqne ... 

Selected ion monitoring is a technique in which only the ions at a limited number ofmjz ratios chosen to be characteristic of the analyte(s)... 

Figure 5.8 Electrospray and transformed electrospray spectra of the light- and heavy-chain antibody fragments of recombinant ritnximab obtained by LC-MS analysis. Reprinted from 7. Chromatogr., A, 913, Wan, H. Z., Kaneshiro, S., Frenz, J. and Cacia, J., Rapid method for monitoring galactosylation levels dnring recombinant antibody production by electrospray mass spectrometry with selective-ion monitoring , 437-446, Copyright (2001), with permission from Elsevier Science.

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