Mass spectrometer analyzers

This chapter should be read in conjunction with Chapter 3, Electron Ionization. In electron ionization (El), a high vacuum (low pressure), typically 10 mbar, is maintained in the ion source so that any molecular ions (M +) formed initially from the interaction of an electron beam and molecules (M) do not collide with any other molecules before being expelled from the ion source into the mass spectrometer analyzer (see Chapters 24 through 27, which deal with ion optics). 

Ions drawn into mass spectrometer analyzer... 

The Z-spray inlet causes ions and neutrals to follow different paths after they have been formed from the electrically charged spray produced from a narrow inlet tube. The ions can be drawn into a mass analyzer after most of the solvent has evaporated away. The inlet derives its name from the Z-shaped trajectory taken by the ions, which ensures that there is little buildup of products on the narrow skimmer entrance into the mass spectrometer analyzer region. Consequently, in contrast to a conventional electrospray source, the skimmer does not need to be cleaned frequently and the sensitivity and performance of the instrument remain constant for long periods of time. 

At the target, clusters are broken up and sample molecular ions, accompanied by some remaining solvent ions, are extracted by an electrical potential through a small hole into the mass spectrometer analyzer (Figure 11.1), where their mass-to-charge (m/z) ratios are measured in the usual way. The mass spectrometer may be of any type. 

All mass spectrometers analyze ions for their mass-to-charge ratios (m/z values) by separating the individual m/z values and then recording the numbers (abundance) of ions at each m/z value to give a mass spectrum. Quadrupoles allow ions of different m/z values to pass sequentially e.g., ions at m/z 100, 101, 102 will pass one after the other through the quadrupole assembly so that first m/z 100 is passed, then 101, then 102 (or vice versa), and so on. Therefore, the ion collector (or detector) at the end of the quadrupole assembly needs only to cover one point or focus for a whole spectrum to be scanned over a period of time (Figure 28.1a). This type of point detector records ion arrivals in a time domain, not a spatial one. 

All mass spectrometers analyze ions for their mass-to-charge ratios (m/z values) and simultaneously for the abundances of ions at any given m/z value. By separating the ions according to m/z and measuring the ion abundances, a mass spectrum is obtained. 

It is worth noting that some of these methods are both an inlet system to the mass spectrometer and an ion source at the same time and are not used with conventional ion sources. Thus, with electrospray, the process of removing the liquid phase from the column eluant also produces ions of any emerging mixture components, and these are passed straight to the mass spectrometer analyzer no separate ion source is needed. The particle beam method is different in that the liquid phase is removed, and any residual mixture components are passed into a conventional ion source (often electron ionization). 

Of course, some substances are sufficiently volatile that a heated inlet line can be used to get them into a mass spectrometer. Even here, there are practical problems. Suppose a liquid or solid is sufficiently volatile, that heating it to 50°C is enough to get the vapor into the mass spectrometer through a heated inlet line. If the mass spectrometer analyzer is at 30°C, there is a significant possibility that some of the sample will condense onto the inner walls of the spectrometer and slowly vaporize from there. If the vacuum pumps cannot remove this vapor quickly, then the mass... 

In a high vacuum (low pressure 10 mbar), molecules and electrons interact to form ions (electron ionization, El). These ions are usually injected into the mass spectrometer analyzer section. 

Ions formed by thermo- or plasmaspray are extracted through a small hole into the mass spectrometer analyzer, where a mass spectrum of the original dissolved sample is obtained. 

A mass spectrometer analyzer disperses ions according to their various m/z values. 

Figure A.3A.3 LC/MS analysis of a dietary supplement consisting of extract of Trifolium pratense (red clover). Reversed-phase C18 HPLC and negative ion electrospray ionization mass spectrometry were used with a quadrupole mass spectrometer analyzer (Agilent also see Table A.3A.1). The map illustrates the abundance of information provided by this hyphenated technique with HPLC mass chromatograms in one dimension and mass spectra in another dimension.

The APCI interface uses a heated nebulizer to form a fine spray of the HPLC eluate, which is much finer than the particle beam system but similar to that formed during thermospray. A cross-flow of heated nitrogen gas is used to facilitate the evaporation of solvent from the droplets. The resulting gas-phase sample molecules are ionized by collisions with solvent ions, which are formed by a corona discharge in the atmospheric pressure chamber. Molecular ions, M+ or M , and/or protonated or de-protonated molecules can be formed. The relative abundance of each type of ion depends upon the sample itself, the HPLC solvent, and the ion source parameters. Next, ions are drawn into the mass spectrometer analyzer for measurement through a narrow opening or skimmer, which helps the vacuum pumps to maintain very low pressure inside the analyzer while the APCI source remains at atmospheric pressure. 

A mass spectrometer analyzes the masses of individual molecules, not the weighted average mass of a group of molecules, so the whole-number masses of the most common Individual isotopes must be used to calculate the mass of the molecular ion. Thus, the mass of the molecular ion for CH4 should be 16. As a result, the mass spectrum of CH4 shows a line for the molecular ion—the parent peak or M peak—at miz =16. 

An impressive diversity of mass analyzers are utilized in modem analytical instrumentation. An overview of the common mass spectrometer analyzers follows, with particular emphasis on linear quadrupole mass analyzers, quadrupole ion traps, and time-of-flight mass analyzers, as they arguably constitute the quantitative MS workhorses of the pharmaceutical industry. The description of alternate analyzer systems should provide a framework in which the utility of these three particular systems provides the most cost-effective analytical mass spectrometer systems for pharmaceutical analysis. 

A number of mass analyzers in use today have been coupled to these sources. These include two- and three-dimensional quadrupole field, time-of-flight (TOF), quadrupole-TOF hybrids, magnetic sector, and Fourier transform mass spectrometers. Paramount to the mass spectrometer analyzer used in the analysis is proper sample preparation. With proper preparation of proteins and peptides, their molecular weights can be determined with high mass accuracy. Conversely, a poorly prepared sample will lead to poor or no mass spectrometer results. For peptides and proteins, the mass accuracy is typically better than 0.01%. 

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