MASS SPECTROMETRY / Overview 337
MALDI
See MASS SPECTROMETRY: Matrix-Assisted Laser Desorption/Ionization
MARINE
See WATER ANALYSIS: Seawater  Organic Compounds; Seawater  Dissolved Organic Carbon;
Seawater  Inorganic Compounds
MASS SPECTROMETRY
Contents
Overview
Principles
Ionization Methods Overview
Electron Impact and Chemical Ionization
Atmospheric Pressure Ionization Techniques
Electrospray
Liquid Secondary Ion Mass Spectrometry
Matrix-Assisted Laser Desorption Ionization
Mass Separation
Ion Traps
Time-of-Flight
Selected Ion Monitoring
Multidimensional
Stable Isotope Ratio
Pyrolysis
Archaeological Applications
Clinical Applications
Environmental Applications
Food Applications
Forensic Applications
Gas Analysis
Peptides and Proteins
Polymerase Chain Reaction Products
Overview
Introduction
R Sleeman and J F Carter, Mass Spec Analytical Ltd.,
Bristol, UK
Mass spectrometry (MS) is an analytical tech-
& 2005, Elsevier Ltd. All Rights Reserved. nique that is used to identify unknown compounds,
338 MASS SPECTROMETRY / Overview
quantify known materials, and elucidate the struc- The analyte may already exist as ions in solution, or
tural and physical properties of ions. The technique it may be ionized by a variety of methods within the
is associated with very high levels of specificity and ion source.
sensitivity, somewhat offset by a high degree of tech- Gas-phase ions are separated in the mass analyzer
nical complexity. Analyses can be accomplished with according to their mass-to-charge (m/z) ratios and
minute quantities  sometimes less than picogram impinge on a detector, where the ion flux is converted
12
(10 g) amounts of material. MS is highly suited to to a proportional electrical current. A data system
the identification of individual components in ex- records the magnitude of these electrical signals as a
tremely complex mixtures. function of m/z and converts this information into a
The history of MS began when the existence of mass spectrum, a graph of ion intensity as a function
electrons and  positive rays was demonstrated by J.J. of mass-to-charge ratio, often depicted as simple his-
Thomson in the early part of the twentieth century. tograms.
Thomson suggested that the technique could be used The mass scale is calibrated by introducing a ref-
to perform chemical analysis, but this was not real- erence compound that yields a well-characterized
ized for several decades. MS was initially used to mass spectrum comprising known masses at suitable
determine the relative abundances of gaseous iso- intervals. A range of calibrants is available for var-
topes and to measure their  exact masses , i.e., ious techniques and applications.
atomic masses with a precision of 1 part in 106 or
better. These fundamental measurements led to Compound Identification
developments in a wide range of physical sciences.
The mass spectrum will typically establish the mo-
lecular weight and structure of the compound being
Principles analyzed. Mass spectra recorded under controlled
conditions are highly reproducible such that the
A mass spectrometer is an instrument that separates
spectrum derived from an unknown may reasonably
charged atoms or molecules according to their mass-
be compared to that of an authenticated standard.
to-charge (m/z) ratio. The unit of mass used is the
When combined with a chromatographic technique
unified atomic mass unit (symbol u), defined as 1/12
mass spectral identification is often regarded as
of the mass of a single atom of the isotope of carbon-
providing unequivocal characterization of a chemi-
12 (12C). The term Dalton (Da) has become widely
cal compound.
accepted in MS as the unit to represent atomic mass.
Large databases or libraries of spectra are com-
The charge on an ion is denoted by the integer
mercially available to assist in compound identifica-
number (z) of the fundamental unit of charge, the
tion in a range of applications, although currently
magnitude of the charge of an electron. In many
these are largely restricted to electron ionization (EI)
cases, the ions encountered have just one charge
spectra.
(z ź 1) so the m/z value is numerically equal to the
Since the rules governing the fragmentation of ions
molecular (ionic) mass in Daltons. Mass spec-
in the gas phase are well established, it is also pos-
trometrists sometimes refer to the  mass of an ion
sible to elucidate the structure of an unknown com-
when they really mean the m/z ratio. The name
pound solely from its mass spectrum.
Thomson (Th) has recently been proposed as a unit
of mass-to-charge ratio in an attempt to alleviate the
Quantification
confusion caused by the increasing importance of
multiply charged ions in MS, but does not yet enjoy Quantification may be achieved by comparing the
widespread acceptance. response of the mass spectrometer from an analyte of
Formation of gas-phase sample ions is an essential interest to the response obtained from the introduc-
prerequisite to mass selection and detection. Ions are tion of a known amount of a standard. Standards are
produced and are accelerated toward an analyzer typically a closely related substance or may be chem-
region that is maintained under vacuum. Either po- ically identical but synthesized by substituting an
sitive or negative ions are selected for analysis. In isotope of one of the elements.
many cases a high proportion of the molecules do not Since the identity of the analyte is already known
ionize and are simply pumped away and not detected. and the requirement is to measure how much is
The sample, which may be a solid, liquid, or vapor, present, it is not necessary to record the full mass
enters the vacuum chamber. Early mass spectrome- spectrum. Selected ion monitoring (SIM) is often
ters required a sample to be gaseous, but the appli- used in such circumstances, where the mass spectro-
cability of MS has been extended to include samples meter (generally coupled with a chromatographic
in liquid solutions or embedded in a solid matrix. technique) monitors only the sample ion and the
MASS SPECTROMETRY / Overview 339
equivalent ion for a suitable internal standard. In this momentum-to-charge ratios of the ions. Ions of
way, very selective conditions for quantifying a larger m/z values follow larger radius paths than
known sample can be devised. ions of smaller m/z values, so ions of differing m/z
values are dispersed in space. By changing the ion
Resolution
trajectories through variations of the magnetic field
strength, ions of different mass-to-charge ratios can
The ability of a mass spectrometer to distinguish be-
be focused onto a detector.
tween ions of different mass-to-charge ratio values is
Double focusing sector field instruments incorpo-
termed as resolution. There are many definitions,
rate a combination of electromagnetic fields (B) and
depending on specific applications and instrument
electric fields (E).
types being used. Traditionally, multisector mass
A common configuration ( forward geometry ) for
spectrometers are considered as high-resolution in-
a sector instrument is the geometry in which a
struments and quadrupole instruments as medium
magnetic sector follows an electric sector analyzer
resolution.
(ESA). This  double focusing combination of energy
A typical multisector instrument can be set to re-
focusing and  angular or  directional focusing and
solve ions at the 20 parts per million level, that is to
energy focusing provides mass resolution high
say an ion of mass-to-charge ratio 500.00 can be
enough to separate ions of the same nominal mass
separated from an ion of m/z 500.01. Time-of-flight
but different chemical formulas. In  reverse geome-
(TOF) instruments can also attain or exceed this
try, the magnetic sector precedes the electric sector.
resolution.
Figure 1 shows a reverse-geometry mass spectrometer
Exact mass measurement can aid in determining
coupled to a gas chromatograph (GC). Such instru-
chemical composition. Every isotope (except carbon-
ments are commonly used for the highly specific de-
12 which is assigned exactly 12.000 00 Da) has a
tection of environmental contaminants such as
unique, noninteger mass. Exact mass measurement
dioxins or performance-enhancing drugs in athletes.
thus allows determination of chemical composition.
With sufficient resolution it is possible to distinguish
between carbon monoxide (CO, 27.995 Da) and nit-
Quadrupole Filters
rogen (N2, 28.006 Da) by exact mass measurement.
Quadrupole mass filters consist of four parallel rods,
illustrated in Figure 2. In such instruments, mass se-
Mass Analyzers lection depends on ion motion resulting from simul-
taneously applied DC and RF electric fields. Scanning
Sector Field Instruments
is accomplished by systematically changing the field
Magnetic sectors deflect the trajectories of ions strengths, thereby changing the m/z value that is
into circular paths of radii that depend on the transmitted through the analyzer. Quadrupole mass
Magnetic sector
Ion source Electric sector
GC inlet
ESA
Magnet
Exit
slit
Electron multiplier
Entrance (source) slit
Ion source
Figure 1 Photograph and schematic diagram of a modern  reverse geometry mass spectrometer coupled to a GC. (Reproduced
with permission from Thermo Electron (Bremen).)
340 MASS SPECTROMETRY / Overview
of the signal from each ion is equal to its orbital
frequency, which in turn is inversely related to its m/z
value. The signal intensity of each frequency is pro-
portional to the number of ions having that m/z
Electron value. The signal is amplified and all the frequency
Ion
multiplier
source Quadrupole components are determined, yielding the mass spec-
trum. Since the pressure in the cell is very low, the ion
Cap orbital motion can be maintained over many cycles
electrodes
and the frequency can be measured with very high
Trapped
precision. FT-ICR instruments can therefore be used
ion region
to generate exceptionally high resolution spectra
with great mass accuracy.
Time-of-Flight Mass Spectrometry
TOF mass analyzers separate ions by virtue of their
different flight times over a known distance. Pulses of
Electron
Ion
ions are ejected from a source and accelerated so that
multiplier
source
ions of like charge have equal kinetic energy. They
Ring
are then directed into a flight tube where lower mass
electrode
ions have greater velocities and shorter flight times.
Figure 2 Schematic diagram of quadrupole and ion trap mass
The travel time from source to detector can be trans-
analyzers.
formed to the m/z value. All ion masses are measured
for each pulse, so TOF mass spectrometers offer high
sensitivity as well as very rapid scanning. They can
spectrometers provide lower resolution than double
provide mass data for very high-mass biomolecules.
focusing instruments but are less costly. The high
scan speeds of quadrupole mass filters render them
highly suited for use in combination with chro-
Ionization Methods
matographic inlet systems.
Compounds are converted into gas-phase molecules
Ion Traps
either before or during the charging or ionization
process, which takes place in the ion source.
Ion trap mass spectrometers operate on a principle
Many types of ionization mode are available; the
similar to a quadrupole mass filter. However, it does
type of compound to be analyzed and the specific
not operate as a filter; the ions are stored for sub-
information required determine which ionization
sequent experiments and analysis. Electric fields are
mode is the most suitable. The ionized molecule
applied to electrodes arranged as a ring electrode in
may subsequently fragment, producing ions of lower
the middle with cap electrodes on each end. Con-
mass than the original precursor molecule. These
ceptually, an ion trap can be considered as a convent-
fragment ions are determined by the structure of the
ional quadrupole folded on itself to form a closed
original molecule.
loop. A comparison with a quadrupole mass analyzer
is shown in Figure 2. Within a selected range of m/z
Electron Ionization
ratios determined by the applied voltages, the device
traps ions in the space bounded by the electrodes. A
In the commonly used EI source (earlier referred to as
mass spectrum is produced by scanning the applied
 electron impact ), ions are generated by bombarding
RF voltages to eject ions sequentially of increasing
the gaseous sample molecules with a beam of
m/z ratio through an end cap opening for detection.
energetic electrons. EI produces a mixture of positive
and negative ions, as well as neutral species. Positive-
Fourier Transform Mass Spectrometry
ion EI mass spectra are more commonly recorded
In a Fourier transform ion cyclotron resonance because these ions form more readily.
(FT-ICR) spectrometer, ions are trapped electrostat- The energy of the electrons (typically 70 eV) is
ically within a cell in a constant magnetic field. An generally much greater than that of the bonds that
orbital ( cyclotron ) motion is induced by the appli- hold the molecule together. Ionization by electrons is
cation of a pulse between the exciter (or emitter) a highly energetic or  hard process that may lead to
plates. The orbiting ions generate a faint signal in the extensive fragmentation that leaves very little or no
detector (or receiver) plates of the cell. The frequency trace of a molecular ion. Because molecular mass and
MASS SPECTROMETRY / Overview 341
structure are not easily determined in the absence of technique for samples where quantity and purity are
a molecular ion, lower energy or  soft ionization not a problem. The sample is first dissolved in a liq-
techniques have been developed based on chemical uid matrix. This is typically a viscous, low vapor
and desorption ionization processes. pressure liquid. A few microliters of this liquid are
placed on a small metal target at the end of a probe
Chemical Ionization
that is inserted into the mass spectrometer. The liquid
surface is then bombarded with a beam of high ki-
Chemical ionization (CI) source is very similar to the
netic energy atoms (xenon) or ions (cesium). Mole-
EI source but the beam of electrons is used to create a
cules sputtered from the surface enter the gas phase
plasma of ionized reagent gas (e.g., isobutane, meth-
and ionize, either by protonation, deprotonation, or
ane, ammonia).
adduction. The resulting ions tend to be stable and
Transfer of a proton to a sample molecule M, from
exhibit little fragmentation.
an ionized reagent gas such as methane in the form of
þ þ
CH5 , yields the [M þ H] positive ion. This process
Matrix-Assisted Laser Desorption Ionization
is less energetic than EI and generally produces less
fragmentation. The fragmentation patterns are not Unlike FAB/LSIMS, matrix-assisted laser desorption
necessarily the same as those of molecular ions, Mþd. ionization (MALDI) uses a crystalline, rather than
Negative ions can also be produced under CI con- liquid, matrix, and a beam of photons, rather than
ditions. Transfer of a proton from M to reagent gas atoms or ions. The net result is a dramatic increase in
or ions can leave [M H] , a negatively charged both sensitivity and mass range of compounds that
sample ion. Addition of an electron to M, a process may be analyzed. The sample is dissolved in a matrix
facilitated by collisionally moderating the energy of and is allowed to crystallize on a stainless-steel
electrons generated in the source, can yield an intense target. The target is then inserted into the mass spec-
M ion. Such ions are often the only ion generated trometer and the surface bombarded with a pulsed
and can be used to detect species with great sen- laser beam. Molecules are desorbed from the surface
sitivity. and ionize, usually by protonation or deprotonation.
Any fragment or multiply charged ions are generally
Desorption Ionization
of low abundance in this ionization mode. The
pulsed nature of the laser excitation renders this
Samples may be desorbed and ionized by an impact
technique compatible with TOF, and the combined
process that involves bombardment of the sample
technique enjoys an almost limitless mass range.
with high-velocity atoms, ions, fission fragments, or
photons of relatively high energy. The impact depos-
Atmospheric Pressure Ionization Techniques
its energy into the sample, either directly or via a
matrix, and leads to both sample molecule transfer Atmospheric pressure ionization (API) techniques
into the gas phase and ionization. encompass a range of techniques in which ionization
Field desorption (FD) is perhaps the simplest tech- occurs external to the mass spectrometer vacuum.
nique, the sample is coated as a thin film onto a spe- Ionization can be achieved by a variety of methods,
cial filament placed within a very high intensity including photoionization, corona discharge at the
electric field. Ions created by field-induced removal of tip of a needle, or by the use of radioisotopes such
63
an electron from the molecule are extracted into as Ni.
the mass spectrometer. Field ionization (FI) is the Atmospheric pressure chemical ionization (APCI)
equivalent process whereby gas-phase molecules are is a simple and robust technique routinely used to
ionized by a high electric potential. These techniques interface the eluent from a high-performance liquid
are sometimes applied to relatively large, polymeric chromatography (HPLC) to a mass spectrometer.
molecules but are not commonplace. The liquid stream passes through a heated nebulizer
into a corona discharge region. Analyte molecules
Fast Atom Bombardment/Liquid SIMS
are ionized and extracted into the mass analyzer.
The techniques of fast-atom bombardment (FAB)/
Electrospray
liquid secondary ionization (LSIMS), developed in
the early 1980s, revolutionized the range of com- Electrospray (ESI) is another example of an API
pounds amenable to analysis by MS and opened up technique.
the field to many areas of biomedical research. Al- The sample is dissolved in a mobile phase and
though now considered insensitive by comparison pumped through a fine stainless-steel capillary main-
with more recently introduced ionization modes, tained at high potential. This creates an electrostatic
FAB still has a role as a rapid, reliable, and robust spray of multiply charged droplets containing the
342 MASS SPECTROMETRY / Overview
sample. At higher solvent flow rates, heat and drying
Sample Introduction Techniques
gas may be needed to increase the rate of droplet
Probe Inlets
evaporation. This technique is sometimes referred to
as pneumatically assisted ESI or Ionspray.
A direct insertion probe may be used for reasonably
After desolvation and subsequent charge concen-
pure volatile solids. The sample is loaded into a
tration, gas-phase ions are produced and propelled
quartz tube on the tip of a rod that is inserted into the
toward the high vacuum mass analyzer. ESI is con-
evacuated source region. The sample is then evapo-
sidered to be one of the  softest ionization techniques
rated or sublimed into the gas phase, usually by hea-
available, i.e., little energy is transferred to the mol-
ting. The gaseous molecules are then ionized (often
ecule other than that required for ionization. Thus,
with accompanying fragmentation) and the ions are
protonated, deprotonated, or cationized molecules
mass analyzed. In some techniques, volatilization
that undergo very little fragmentation are generated,
and ionization occur at the same time.
even from highly polar, thermally labile molecules.
ESI can impart many charges (z), usually in the
Septum Inlets
form of protons, to amenable large molecules such as
Heated reservoir septum inlets may be used for pure
proteins, and thus compounds with molecular masses
gases or volatile liquids, comprising a heated re-
in the tens of thousands can be analyzed with mass
servoir with a small restriction  bleed into the ion
spectrometers with m/z ranges of a few thousand.
source. The sample is injected into the reservoir
Molecular mass can often be determined to a preci-
through a septum. This method is commonly used to
sion in the order of one part in 10 000 or better. ESI is
introduce reference materials for calibration.
particularly compatible with liquid separation meth-
ods and has become a widely used method in
Chromatographic Techniques
biological and pharmaceutical analysis, where iden-
tification is achieved through deconvolution of the To obtain the mass spectrum of a single constituent
envelope of peaks formed with multiple charge states. of a mixture, the individual components often need
to be separated prior to analysis. Separation is nec-
Choice of Ionization Technique
essary for unambiguous identification because two
EI and CI are generally the techniques of choice for compounds present in the source region simultane-
small (o800 Da), volatile, thermally stable com- ously create a mixed spectrum and even simple com-
pounds. pounds can generate many fragment ions. The
CI tends to give molecular weight information and historical combination of GC and MS (GC MS) al-
EI, with the greater fragmentation, provides struc- lows compounds in the vapor phase to enter the mass
tural information. spectrometer so that the components of mixtures can
FAB/LSIMS is useful for larger (t5000 Da) be detected and analyzed sequentially.
involatile, polar, thermally unstable molecules, such The challenge in interfacing a mass spectrometer
as peptides, small proteins, and other biopolymers. to a separation system like a gas or liquid chro-
However, this technique has now largely been super- matograph is maintaining the required vacuum in the
seded by ESI and MALDI. mass spectrometer while introducing flow from
MALDI is suitable for similar compounds to those the chromatograph. Interfaces that restrict or reduce
amenable to FAB, but affords much greater sen- the gas flow into the mass spectrometer (e.g., flow
sitivity. Biopolymers with molecular weights above splitters or devices that differentially remove carrier
300 000 Da have been successfully analyzed. gas from the GC effluent) initially made the combi-
ESI is suitable for similar compounds to MALDI, nation of GC and MS an extremely widely used
with possibly a slightly reduced sensitivity and mass technique. The low gas flows typical of capillary GC
range. The tendency to produce multiply charged now permit direct connection to mass spectrometers.
ions brings the mass-to-charge ratios of high molec- More recently, liquid chromatography (LC), su-
ular weight proteins well within the range of inex- percritical fluid chromatography (SFC), and CZE
pensive mass spectrometers. This has fuelled an devices connected to mass spectrometers have been
explosion in biochemical applications of MS and used to separate components of complex mixtures
has spawned the developing fields of proteomics, prior to mass analysis. When vaporized, the solvent
genomics, and metabonomics. from an LC represents a volume of 100 1000 times
ESI is frequently interfaced with chromatographic greater than that of a carrier gas used in GC. Inter-
techniques such as HPLC, capillary zone elect- faces developed commercially have solved the
rophoresis (CZE), and capillary electrochromato- problem of eliminating this gas load by using com-
graphy (CEC). binations of heating and pumping, sometimes with
MASS SPECTROMETRY / Overview 343
the assistance of a drying gas stream. The inlets for standard and switching between the gas phase tran-
higher flow rates (as in analytical LC) employed in sitions can lead to very high specificity. This technique
LC/MS systems in routine use are primarily APCI is known as selected reaction monitoring (SRM), and
and ESI. is frequently used for quantification. Fragmentation is
Particle beam interfaces, thermospray, and  dy- usually achieved in a collision cell pressurized with an
namic FAB have also been used as LC continuous- inert gas such as argon. Collision of ions with atoms
flow injection techniques, but these have largely been in the cell produces fragments by a process known as
superseded. collision induced dissociation (CID). Other approach-
For GC MS, LC MS, or other combinations, the es have been used to cause fragmentation, such as
data consist of a series of mass spectra acquired lasers, electron beams, and surface collisions.
sequentially in time. To generate this information, In cases where  soft ionization techniques are
the mass spectrometer scans the mass range repet- used, the molecular weight of the sample may be
itively during the chromatographic run. The intensi- observed but the lack of in-source fragmentation
ties of all the ions in each spectrum can be summed, means that little structural information is available.
and this sum plotted as a function of chromatogra- A product ion mass spectrum acquired with a tan-
phic retention time to give a total ion chromatogram dem mass spectrometer can yield this structurally
(TIC) whose appearance is similar to the output of a significant information.
conventional chromatographic detector. Each peak In the technique of precursor ion scanning the sec-
in the TIC represents an eluting compound that can ond mass spectrometer is set statically to transmit
be identified by interpretation of the mass spectra product ions of only one selected mass-to-charge ra-
recorded for the peak. The intensity at a single mass- tio. This mass is monitored continuously whilst the
to-charge ratio over the course of a chromatographic first mass spectrometer is scanned. A signal will be
run can be displayed to yield a selected ion current detected only when a precursor ion fragments to form
profile or mass chromatogram. This technique can be the product ion that is monitored. This technique is
used to find components of interest in a complex often used to screen for compounds of related struc-
mixture without having to examine each individual ture, such as the metabolites of a known drug.
mass spectrum. Another tandem screening method is known as
constant neutral loss scanning. Here, both mass spec-
trometers are scanned simultaneously but are offset
Mass Spectrometric Techniques
corresponding to the difference between precursor
and product ion masses. A signal only appears when a
Selected Ion Monitoring
precursor ion yields a product ion with the mass dif-
SIM is frequently used for the quantitative determi-
ference selected. This technique can be used to screen
nation of specific analytes by MS, usually in combi-
for compounds that contain a specific structural fea-
nation with a chromatographic separation. The mass
ture that yields a common fragmentation process.
spectrometer is used to monitor a limited number of
Tandem MS can be performed using sector, quad-
ions characteristic of target compounds, rather than
rupole, and TOF instruments. However, each stage
to acquire a complete spectrum. The effect is that the
of mass analysis requires a separate mass analyzer.
instrument spends a greater time recording ions from
Different mass analyzers are often combined to form
the analytes of interest with a resulting increase in
tandem instruments for specific applications, e.g.,
both sensitivity and selectivity. This is a very sensitive
Q-TOF.
technique and for some compounds it is possible to
Ion trap or ICR mass spectrometers permit MS/MS
15
detect at the femtogram (10 g) level.
product ion experiments to be conducted sequenti-
ally in time within a single mass analyzer. A number
Tandem or Multistage Mass Spectrometry
of sequential experiments, termed MSn, may be per-
(MS/MS, MSn)
formed.
Tandem MS is used to provide more information than Modern TOF mass spectrometers incorporate a
can be afforded by a single mass spectrometer and is reflectron unit and the facility to analyze what are
known as postsource decay ions. The spectra pro-
widely used for screening complex matrices such as
blood and urine. Analysis is achieved, in effect, by duced are similar to product ion spectra and can be
performing two stages of SIM. The first mass spec- enhanced by the inclusion of a collision cell.
trometer is set to transmit the  precursor ion of in-
Stable Isotope Ratio Mass Spectrometry
terest into a region where fragmentation occurs. One
of the  product ions is monitored by a second mass Although often presumed to be constant, natural
spectrometer. Selection of an appropriate internal isotope abundance ratios show significant and
344 MASS SPECTROMETRY / Principles
characteristic variations when measured very pre- chemical constituents. Elemental MS provides quan-
cisely. In stable isotope ratio mass spectrometry titative information about the concentrations of
(IRMS), element isotope ratios are determined very those elements. The decomposition of the sample
accurately and precisely. Typically, single focusing into its constituent atoms and ionization of those
magnetic sector mass spectrometers with fixed mul- atoms occurs in a specially designed source. The ion
tiple detectors (one per isotopomer) are used. Com- source used in elemental MS is ordinarily an atmos-
plex compounds are reduced to simple molecules pheric-pressure discharge such as inductively coupled
prior to measurement, for example, organic com- plasma (ICP) or a moderate-power device such as
pounds are combusted to CO2, H2O, and N2. Iso- glow discharge (GD). The resulting atomic-ion beam
tope ratio measurements are useful in a wide range of is then separated by a mass analyzer and the signal
applications, for example, metabolic studies using used to determine the sample composition. With an
isotopically enriched elements as tracers; climate ICP employed as an ion source, solution detection
studies using measurements of temperature-depend- limits down to the parts per trillion level are possible
ent oxygen and carbon isotope ratios in foraminifera; in favorable cases, while with the glow-discharge
rock age dating using radiogenic isotopes of elements source, solid metal samples can be analyzed directly
such as lead, neodymium, or strontium; and source and their elemental composition determined over a
determinations using carbon isotope ratios (for ex- million-fold range of concentrations. Isotopic infor-
ample, to discriminate between naturally occurring mation is readily available.
substances and petroleum-based synthetic materials).
See also: Gas Chromatography: Mass Spectrometry.
Pyrolysis Mass Spectrometry
Liquid Chromatography: Liquid Chromatography Mass
Spectrometry. Mass Spectrometry: Ionization Methods
Pyrolysis is the thermal degradation of complex ma-
Overview; Mass Separation; Stable Isotope Ratio.
terial in an inert atmosphere or a vacuum. Molecules
cleave into smaller, volatile fragments called pyroly-
Further Reading
sate. In pyrolysis MS (PyMS), the pyrolysate is di-
rectly analyzed by MS to produce a chemical profile
American Society for Mass Spectrometry website,
or fingerprint of the complex material analyzed. The
www.asms.org
development of PyMS was largely driven by its ap-
Armentrout PB (2003) In: Gross ML and Caprioli RM
plicability to the characterization of microorganisms
(eds.) Encyclopedia of Mass Spectrometry, vol.1: Theory
and has now largely been supplanted by the appli- and Ion Chemistry. Amsterdam: Elsevier.
Ashcroft AE (1997) Ionization Methods in Organic Mass
cation of MALDI in this field. In contrast, pyrolysis
Spectrometry. Cambridge: Royal Society of Chemistry.
GC/MS (Py-GC/MS) still finds numerous applica-
British Mass Spectrometry Society website, www.bmss.
tions in the analysis of complex synthetic and
org.uk
biological polymers.
Chapman JR (1993) Practical Organic Mass Spectrometry,
2nd edn. New York: Wiley.
Elemental Mass Spectrometry
de Hoffmann E and Stroobant V (2001) Mass Spectro-
Elemental MS is applied mostly to inorganic mate-
metry Principles and Applications. Chichester: Wiley.
rials, to determine the elemental composition of a
Sparkman OD (2000) Mass spectrometry desk reference.
sample rather than the structural identities of its Pittsburgh, PA: Global View Publishing.
Principles
K J Welham, University of Hull, Hull, UK
investigation, separating these ions according to their
mass-to-charge ratio and recording the relative abun-
& 2005, Elsevier Ltd. All Rights Reserved.
dances of the separated ion species as a mass spec-
This article is a revision of the previous-edition article by
trum. Many types of mass spectrometers have been
A Roberts, pp. 2787 2795, & 1995, Elsevier Ltd.
developed to fulfill the above definition. The widely
differing nature and physical state of sample mate-
rials has resulted in a variety of techniques for sa-
Introduction
mpling, ionization, ion storage, mass separation, and
The mass spectrometer is an instrument capable of ion recording. This article on the basic principles of
producing a beam of ions from a sample under mass spectrometry (MS) will cover the historical