Physical Bases of Mass Spectrometry

Because mass spectrometry deals with positive or negative ions it is necessary to ionize a sample after its introduction onto an ion source. There are several dozens of ionization methods. Some of them are used very commonly, others only in unique experiments. The popularity of a method may reach its peak at some stage and then with the appearance of new more efficient techniques it can decline (see Chapter 2, Section 2.1). 

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Two general types of the application of mass spectrometry should be emphasized. One is the detection and characterization of compounds introduced into the mass spectrometer. In this case the mass spectrometer can be considered as a powerful detector. It is able to characterize individual compounds, or work online with (chromatographic) separation techniques. Many applications of mass spectrometry, including analytical aspects, are based on the fact that this method involves physical or chemical transformations of the compounds being studied. These transformations may include evaporation, desolvation, electron transfer to or from the analyte, and chemical transformations before or after ionization. Chemical transformation can involve the formation of new bonds, or bond cleavage in ions of the compound under study. 

Figure 3 Schematic illustration of the liquid-based thermospray ionization modes. Reprinted with permission from Vestal ML (1983) InternationalJournal of Mass Spectrometry and Ion Physics 46 193-196, 1983, Elsevier Science.

Molecules can be small, like CH4, large, or very large, like some biopolymers with molecular weights of millions of daltons. They can be organic, inorganic, polar, apolar, etc. Mass spectrometry can study all of them. However, one ionization technique cannot ionize all kinds of molecules but different ionization techniques are now available. Their choice is based on the chemico-physical properties of the molecule, such as molecular weight, polarity, thermal stability, etc. 

Most nitrile oxides are unstable, some of them are explosive. This fact hinders the study of their physical properties. Nevertheless, there are a number of publications concerning not only stable but also unstable nitrile oxides. In particular, mass spectral data for nitrile oxides among other unstable compounds containing an N+-X bond are summarized in a review (9). In such studies, the molecular ions must be generated using indirect procedures, including dissociative electron ionization, online flash-vacuum pyrolysis mass spectrometry, or ion-molecular reactions. Their characterization is mainly based on collisional activation and ion-molecular reactions. 

In practice, it is not sufficient for an object to have an isotopic composition that cannot be explained by radioactive decay or mass-dependent fractionation effects. The object must also have physical and chemical characteristics making it unlikely to be a product of solar system processes. For example, millimeter- to centimeter-sized refractory inclusions from primitive chondrites have been shown to contain small (parts in 103 to 104) isotopic anomalies in many elements. However, based on the size, composition, physical characteristics, and abundance of the inclusions, it is generally believed that these objects formed within the solar system. They preserve small isotopic anomalies because they did not form from a representative sample of the bulk solar system (see Chapters 7 and 14). So, isotopic anomalies can indicate either that an object is itself presolar or that it formed in the solar system from precursor material that was not fully homogenized in the solar system. As mass spectrometry has become more precise, small isotopic anomalies of the second type have shown up in a wide variety of chondritic materials. As we discuss below and in Chapter 7, these anomalies and bona fide presolar grains can be used as probes of processes in the early solar system. 

Laval University was one of the first Canadian universities to hire a theoretical chemist. Wendell Forst arrived in 1961 and developed a research program based on the theory of unimolecular reactions75 and quantum chemistry. He maintained ties with experimental physical chemistry through a strong interest in mass spectrometry and gas phase kinetics. In many of his papers he sought analytical solutions to fundamental problems.76 In 1986, after a quarter-century at Laval, he moved to the University of Nancy in France. 

Mass spectrometry is based on the physical properties of the atomic nucleus. The atomic nucleus of any chemical element consists of protons and neutrons. In an electrically neutral atom the number of positively charged protons in the nucleus equals the number of negatively charged electrons in the shells. The number of protons (Z = atomic number) determines the chemical properties and the place of the element in the periodic table of the elements. The atomic number Z of a chemical element is given as a subscript preceding the elemental symbol (e.g., jH, gC, 17CI, 2eF or 92 )-Besides the protons, uncharged neutrons with nearly the same mass in comparison to the protons (m = 1.67493 x 10 kg versus nip = 1.67262 x 10 kg) stabilize the positive atomic nucleus. In contrast to the mass of the protons and neutrons in the nucleus, the mass of the electrons is relatively small at = 9.10939 x 10 kg. 

In drug preparations, sensitivity is not a particular problem as there is always sufficient of the active constituent present. Suitable extraction procedures should be carried out and each fraction should then be subjected to chromatographic analysis. The mass spectra, together with the appropriate retention parameters, may then be used for identification purposes. In many cases mass spectrometric analysis is undertaken as confirmation of an identification based on the physical characteristics such as size, colour, markings, etc., of the tablet or capsule. Mass spectrometry may be used not only to identify the major components but also the trace impurities. This information may be used for quality control purposes, and may enable the route of manufacture of certain drugs to be determined. 

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