How does a mass-spectrometer work?

Mass spectrometry is the analytical technique that provides the most structural information for the least amount of analyte material. It provides qualitative and quantitative information about the atomic and molecular composition of inorganic and organic materials and their chemical structures. As an analytical technique it possesses distinct advantages such as:

1. Increased sensitivity over most other analytical techniques because the analyzer, as a mass-charge filter, reduces background interference

2. Excellent specificity from characteristic fragmentation patterns to identify unknowns or confirm the presence of suspected compounds.

3. Information about molecular weight.

4. Information about the isotopic abundance of elements.

A few of the disadvantages of the method is that often fails to distinguish between optical and geometrical isomers and the positions of substituent in o-, m- and p- positions in an aromatic ring. Also, its scope is limited in identifying hydrocarbons that produce similar fragmented ions.

The mass spectrum obtained is a fingerprint for each compound because no two molecules are fragmented and ionized in exactly the same manner.

History of Mass Spectrometry

 

Mass spectrometry (MS) was developed at the beginning of the 20^th century by J.J. Thomson (1910) Dempster (1918) and F.W. Aston (1920) to separate and identify isotopes. In the thirties, Smyth (1931) and Tate (1935) recognized that ionization of organic molecules by electron impact leads to characteristic fragment ions which can be measured by mass spectrometry and which allow conclusions on the structure of the chemical compound.

In the forties, mass spectrometry was first commercially used in the petroleum and rubber industry of the U.S.A.

In the sixties mass spectrometry was introduced to organic chemistry as a powerful spectroscopic method, especially for the determination of accurate molecular masses and for the calculation of elemental compositions. It was also used for the identification of unknown compounds, since the mass spectrometer reproducible forms fragment ions which are typical for an organic molecule.

In the seventies, mass spectrometry was directly coupled with chromatographic methods such as gas chromatography. This coupling significantly improved the analysis of complex mixtures of organic compounds because of its high specificity and sensitivity.

In the eighties GC-MS became the most powerful method for the analysis of organic compounds such as drugs, pesticides, pollutants and their metabolites in clinical, forensic and food chemical determinations. It is also used in doping control as well as in environmental and occupational toxicology. 

The Basics of  Mass Spectrometer / Mass Spectrometry

Mass spectrometers use the difference in mass-to-charge ratio (m/z) of ionized atoms or molecules to separate them.  Therefore, mass spectrometry allows quantitation of atoms or molecules and provides structural information by the identification of distinctive fragmentation patterns.

The general operation of a mass spectrometer is:

1. Create gas-phase ions
2. Separate the ions in space or time based on their mass- to-charge ratio 
3. Measure the quantity of ions of each mass-to-charge ratio

  A schematic design of a mass spectrometer is shown in Fig. 1

 

Fig. 1: Schematic design of a mass spectrometer.

The sample is introduced through the inlet into the ion source which is under vacuum. The sample components are ionized in the ion source and the ions formed are accelerated in the direction of the mass analyzer. Without the vacuum, the molecular mean free path would be very short and ions would collide with air molecules before they could reach the mass analyzer. The resulting distribution of molecular fragments is characteristic of the molecule and it is called a mass spectrum.

The mass spectrum obtained consists of a unique bar graph in which the height of the bars represents the relative abundance of the most abundant ions of each individual compound as a function of the mass (Fig. 2). These ions give information concerning the molecular weight and the most electronically stable ion fragments from the original molecule. These unique fragments may be matched or interpreted to characterize a molecule based on its atomic structure. A typical electron impact (EI) mass spectrum of acetone is shown in Fig. 2. Ion fragments appear at the mass-to-charge ratios (m/z) 43 and 15 (the m/z = 15 is not shown). These ion fragments represent the parts of the molecule that broke off from the parent molecule. Also the parent molecule of acetone appears at m/z = 58, a valuable information about the molecular weight of the analyzed compound.

 

Fig. 2: Electron-impact mass spectrum of acetone showing the molecular ion at m/z 58 and the base peak at m/z 43.

The ion sources used for the ionization of samples are: chemical ionization (CI), atmospheric pressure chemical ionization (APCI), electron impact (EI), electrospray ionization (ESI), thermospray ionization (TI), fast atom bombardment (FAB), matrix assisted laser desorption (MALDI).

The two most accepted ways to create ions in mass spectrometers are by electron impact (EI) and chemical ionization (CI). The largest amount of mass spectra have been obtained by electron impact.

Electron impact (EI) is the oldest and most simple technique. The ionization source is heated and is under vacuum so most samples will vaporize and then ionize. Ionization is usually accomplished by impact of a high energetic (70 eV) electron beam. The electrons are drawn out from a tungsten filament when a voltage of 70 eV is applied. The voltage applied to the filament defines the energy of the electrons.

These high energy electrons strike the neutral analyte molecule causing ionization – loss of an electron – and fragmentation. This ionization technique produces almost exclusively positive ions:

M    +    e^-      →   M⁺   + 2e^-

The EI technique is applicable to all volatile compounds ( >103 Da) and gives reproducible mass spectra with fragmentation to provide structural information.

The Chemical Ionization (CI) is the other major technique for ionizing samples. In CI, a reagent gas like methane is admitted to the ionization chamber where it is ionized, producing a cation that undergoes further reactions to produce secondary ions. For example:

CH₄  +  e^-     →      CH₄⁺   +    2e^-

                                            CH₄  +    CH₄⁺    →      CH₅⁺   +   CH₃

The secondary ion produced CH₅⁺ in this case serves as a reagent to ionize the sample gently. Usually this process results in less fragmentation and more simple spectra. The major peaks that normally result are M+1, M, M-1, M+29 where M is the mass of the analyte under examination.

The CI technique gives mainly molecular weight information.

The mass analyzers used: quadrupoles, magnetic sectors, time-of –flight (TOF), Fourier transform and quadrupole ion traps.

The detectors used are the electron multiplier or Faraday cup. These devices have high gain amplification characteristics in the range of 10⁷. The high gain capabilities of the electron multiplier are what allow the detection of very low femtoampere ion currents.

REFERENCES

1. D. Harvey,  “Modern Analytical Chemistry”, McGraw-Hill Companies Inc., 2000
2. “Gas Chromatography”, J. Willett, John Wiley &Sons, 1987
3. K. Pfleger et al. “Mass Spectral and GC Data of Drugs, Poisons, Pesticides, Pollutants and their Metabolites”, 2^nd Edition, VCH, 1992
4. H.M. McNair, J.M. Miller, “Basic Gas Chromatography”, John Wiley &Sons, 1997