Chromatography: Combined Chromatography and Mass Spectrometry
Z Zhang, X Hu, and P Li, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, China
ã 2016 Elsevier Ltd. All rights reserved.
Introduction
The advanced analytic technologies are revealing a complex pro-
file regarding the food and health research. Most foodstuffs are
produced from living organisms and tissues, thus reflecting the
complexity of the biological systems they are coming from.
Generally, two types of opposite food components, namely, ben-
eficial and hazardous ones, gain the emerging attention. These
components play a key role in food nutritional, functional, or
hazardous properties. Among the toolkits of techniques devel-
oped to investigate food at wide scale including small molecules,
peptide, and proteome, chromatography combined with MS has
gained popularity especially because of its ability to handle com-
plex food matrices. The chromatography–MS methods demon-
strate high resolution ratio, specificity, speed, and reliability of the
analytic response in a high-throughput mode. For these reasons,
chromatography–MS methods have been extensively employed
in food analysis.
In this article, applications of chromatography–MS to food
safety and quality is discussed in detail, including detection,
identification, and quantification. In this way, the identifica-
tion and determination of food could be addressed, especially
for the certification and traceability of foodstuffs. Moreover,
the relationship between structure and function in food
systems could be clarified.
Combined Chromatography to MS Strategies
MS method is based on the production of ions, which are
subsequently separated or filtered according to their mass-to-
charge (m/z) ratio and then detected. The resulting mass
spectrum is a plot of the (relative) abundance of the generated
ions as a function of the m/z. It provides excellent selectivity,
which is of utmost importance in quantitative trace analysis.
The mass spectrometer is a highly sophisticated and comput-
erized instrument, which basically consists of ion source, a
mass analyzer, and a detector. In principle, liquid chromatog-
raphy (LC), gas chromatography (GC), and capillary
electrophoresis (CE) are used as the separation technique,
while the mass spectrometers are employed as a detector. The
different physical and chemical properties between analytes
and their relative affinity for the stationary/mobile phases
promote their separation. The molecules are retained in the
column and then elute (come off) from the column at different
times (retention time) that depend on the analyte affinity for
the mobile phase. This allows the mass spectrometer down-
stream to capture, ionize, accelerate, deflect, and detect the
ionized molecules separately, by breaking each molecule into
ionized fragments and detecting these fragments using their
m/z. However, online chromatography–MS systems offer addi-
tional value, especially in terms of selectivity that allows sensi-
tive and specific analysis in food for various purposes.
Encyclopedia of Food and Health http://dx.doi.org/10.1016/B978-0-12-384947-2.00158-6
Mass Spectrometer
A mass spectrometer contains three major components,
namely, an ion source, a mass analyzer, and a detector. The
analyte previously separated from other analytes and
the matrix bulk eluted to the ion interface, where a portion
of the sample is converted into ions. The ions that meet
certain characteristics are trajected through the mass analyzer
and onto the detector. The mass analyzer is used to sort the
ions (according to their m/z values) and to calculate their
abundances.
With the ion source, the target of interest is ionized and
then transported by magnetic or electric fields to the mass
analyzer. For gases and vapors, electron ionization (EI) and
chemical ionization (CI) can be applied. For liquid and solid
biological samples, electrospray ionization (ESI) and matrix-
assisted laser desorption/ionization (MALDI) are the most
commonly used ionization sources. Inductively coupled
plasma (ICP) sources can carry out cation analysis, although
it appears seldom in food analysis. In the combination of
HPLC/GC to MS, the ionization sources are classified accord-
ing to hard and soft ionization of the molecule. Hard ioniza-
tion types, such as EI, provide a high degree of fragmentation
and important information for structure of unknown com-
pounds. However, the EI source is not the most appropriate
for HPLC–MS, because of the short EI shelf life at atmospheric
pressure. On the country, EI source can be used in GC–MS
due to its high vacuum. Soft ionization indicates that ions are
formed using lower residual energy, such as fast atom bom-
bardment (FAB), chemical ionization (CI), atmospheric pres-
sure chemical ionization (APCI), electrospray ionization
(ESI), and MALDI. These sources provide mostly the molecu-
lar ions (or protonated or deprotonated molecules and few
fragments).
Mass analyzers separate the ions according to their m/z ratio
by using an electric and/or magnetic field. There are different
types of mass analyzers. Time-of-flight (TOF) analyzer records
the pass-through time by using an electric field to accelerate the
ions with the same potential, thus allowing the most rapid
reach of lighter ions. Nowadays, TOFs provide accurate m/z.
Quadrupole mass filter can chose ions in a certain range of m/z
by using oscillating electrical fields and can filter m/z as the
quadrupole ion trap. Three-dimensional quadrupole ion trap
can trap and eject ions sequentially. A linear quadrupole ion
trap can trap ions in a two-dimensional quadrupole field,
instead of a three-dimensional quadrupole field as in a 3-D
quadrupole ion trap. In the Orbitrap method, ions are electro-
statically trapped in an orbit around a central, spindle-shaped
electrode.
The final element of the mass spectrometer is the detector.
The detector records the charge induced or the current pro-
duced when an ion passes by or hits a surface. The electron
multiplier, Faraday cups, or ion-to-photon detectors are com-
monly used.
79
80 Chromatography: Combined Chromatography and Mass Spectrometry
GC–MS
GC–MS method combines the features of GC and MS to iden-
tify different substances within single food sample. The use of a
mass spectrometer as detector in GC was developed during the
1950s after being initially assembled by James and Martin in
1952. GC involves an oven and inside of it capillary column
with proper dimensions (length, diameter, and film thickness)
and optimized phase properties that helps to separate the
targets of interested by volatilization using a temperature gra-
dient of the oven. The mobile phase is an inert carrier gas
(as helium or nitrogen), while the stationary phase is a micro-
scopic layer of liquid or polymer on an inert solid support
(silica). In principle, the targets of interest are volatilized and
then interact with the GC stationary phase coated in the col-
umn walls. Each compound elutes at a different time (reten-
tion time) depending on their boiling point and affinity by the
stationary phase.
The typical components of GC instruments are carrier gas,
flow controller, sample injector, column oven, column, and
detector (any type of mass analyzer). In the GC separation
process, a certain volume of gaseous or liquid sample is
injected into the column head by using, usually, a microsyringe
(solid-phase microextraction fibers can also be used). The
carrier gas sweeps the targets through the GC column and,
then, the analyte elute of the column when the oven temper-
ature raises its boiling point. Different adsorption strengths
between the targets and stationary-phase materials allow also
variations in retention time, in favor of the identification and
determination by MS.
Recently, comprehensive two-dimensional (2-D) GC, or
GC
GC  originally developed in 1991 by Professor
Phillips  was employed to separate targets that are difficult
to separate by conventional GC. The two GC columns are
connected sequentially, the 1-D column is a conventional
one and the 2-D column is a short fast one. Between the 2-D
columns, a modulator is employed to collect small fractions of
the effluent from 1-D, focus them as a narrow pulse, and
transfer them to the 2-D. This so-called modulation cycle is
repeated throughout the 2-D GC run. For example, a typical
modulation is the thermal modulation. The liquid nitrogen is
used to immobilize all the components eluting from 1-D. A
hot stream pulse mobilizes a part of the compounds through
the second column, where the 2-D elution starts again.
GC–MS method offers high sensitivity and resolution
power, excellent reproducibility, and extensive and highly
reproducible fragmentation, providing excellent identification
potential through well-established databases, such as the NIST
library. Other advantages are the easy use of the technique and
its low cost. The major disadvantage is that GC–MS is by its
nature limited to the analysis of small volatile molecules and
molecules that can be made volatile. The problem of by-
product formation and degradation needs consideration.
The GC-MS methods allow much finer degree of substance
identification than either of the unit used separately. It is
difficult to make an accurate identification by single GC or
MS methods. The MS process normally requires a pure sample,
while GC using a traditional detector (e.g., flame ionization
detector) cannot differentiate between molecules that coeluted
in the same peak. GC–MS method reduces the possibility of
error, because two different molecules that behave in the same
manner in GC and MS are very rare. Therefore, when an
identifying mass spectrum appears at a characteristic retention
time in a GC–MS analysis, it typically increases certainty that
the analyte of interest is in the sample. Two different molecules
can also have a similar pattern of ionization in a mass spec-
trometer (isobaric interferences). However, accurate mass
instruments reduce or eliminate the possibility of these
interferences.
LC–MS
LC–MS is a powerful technique that has very high sensitivity
and selectivity and so is useful in many applications such as
food safety. This separation principle is similar to GC (different
affinities of the analytes for the stationary/mobile phases).
However, in GC, the analyte separation is between the liquid
stationary phase and the gas mobile phase, while, in HPLC, the
analyte separation is between the solid stationary phase and
the liquid mobile phase. Then, analytes are separated accord-
ing to their polarity independently of whether they are volatile
or not. In HPLC, the separation is forced by a liquid at high
pressure (as the mobile phase) through a column. This HPLC
column is previously packed with a stationary phase generally
composed of irregularly or spherically shaped particles. Usu-
ally, octadecylsilyl (C18) is used as stationary phase with pure or
pH-adjusted water–organic mixtures (as water–acetonitrile or
water–methanol), which is termed reversed-phase liquid chro-
matography (RP-LC). Silica gel is also can be applied as station-
ary phase with neat or mixed organic mixtures, which is called
normal-phase liquid chromatography (NP-LC). RP-LC is most
often used because of its superior separation capabilities.
LC–MS is currently (probably) the most widely used mass
spectrometry technology, due to its ability to separate and
detect a wide range of molecules. The method allows for the
collection of both qualitative and quantitative data and can
achieve pgL1level of detection.
The combination of the separating potential of liquid chro-
matography and the analyzing power of mass spectrometry
makes LC–MS a highly useful tool for analytical chemists.
Due to its high selectivity and sensitivity, it is finding increasing
use in the analysis of a wide range of substances in complex
mixtures. The major challenge in coupling of LC with MS is
posed by the fact that gas-phase ions must be produced in
order to obtain a mass spectrum.
There are many types of LC–MS interface, such as ESI, APCI,
atmospheric pressure photoionization (APPI), and MALDI.
Currently, there are mainly two types of API interfaces. One is
ESI, which is best suited to ionic compounds with high polarity
and the other APCIs. As already mentioned, ESI is a soft ioni-
zation technique, producing little fragmentation. For better
structural information, ESI interface can be coupled with
tandem MS (ESI-MS/MS).
CE–MS Method
CE includes a group of electrokinetic separation methods car-
ried out in submillimeter capillaries and in micro- and nano-
fluidic channels. In these methods, analytes migrate through
electrolyte solutions under the influence of an electric field.
 Chromatography: Combined Chromatography and Mass Spectrometry
Analytes can be separated according to ionic mobility;
additionally, they may be concentrated by means of gradients
in conductivity and pH. The identity of sample components
can be established by direct coupling of the capillary electro-
phoresis with mass spectrometers. Commonly, to connect
both instruments, the capillary outlet is introduced into an
ESI source modified to introduce a sheath liquid that closes
the electrical circuit. CE-MS offers a powerful tool for the
targeted analysis of polar metabolites, such as amino acids,
organics acids, and nucleotides with superior resolution and
sensitivity.
Application in Food Analysis
Food products can be regarded as complex mixtures and
consist of beneficial and hazardous compounds that naturally
occur in food or are introduced during food processing. Bene-
ficial food components include lipid, carbohydrate, polyphe-
nols, carotenoid, amino acids, peptides, and proteins, while
the hazardous ones consist of mycotoxin, marine toxin, plant
toxins, pesticide, and veterinary drugs. As example of natural
beneficial food compounds, lipids such as fats and sterols are
able to store energy and act as structural components of cell
membranes. The positive health benefits associated with
the consumption of omega-3 fatty acids on infant develop-
ment, cancer, cardiovascular diseases, and various mental
illnesses, such as depression, attention-deficit hyperactivity
disorder, and dementia, should also be kept in mind. On the
contrary, toxic substances generally originating from crop pro-
tection treatments against pest, agrochemical treatments, or
packaging materials have been frequently found in foodstuffs.
Pesticide residues can cause acute and chronic health effects in
human and livestock, ranging from simple irritation of the skin
and eyes to the destruction of the nervous system, reproductive
problems, and even cancer. All these compounds, toxic or
beneficial, can be determined using chromatography com-
bined with mass spectrometry. In the next section, the deter-
mination of both, beneficial and hazardous compounds, in
food is discussed.
Analyzing Beneficial Food Components via
Chromatography–MS
Lipid
Lipids are macronutrients that contribute significantly to the
nutritional and sensory value of food. Lipids can be found in
various forms, such as free fatty acids, acylglycerols, phospho-
lipids, sphingomyelins, glycosphingolipids, steroids, and bile
acids. Some lipids have simple structure (as fatty acids), but
many others have complex and variable structures. The struc-
tures can be ascertained and completely resolved by HPLC–MS
or GC–MS methods, helping to establish the structure/func-
tion relationship. HPLC–MS method is one of the most pow-
erful tools for the analysis of lipid components in food. Lipid
content from various foodstuffs has been extensive investi-
gated. To simplify sample preparation, HPLC–MS method
has been an attractive alternative. The main trend of diverse
lipids’ analysis is the employment of HPLC–MS methods.
Triacylglycerols, fatty acids, carotenoids, and phospholipids
81
found in various foodstuffs have been studied in detail via
HPLC–MS method. In addition, the use of tandem mass spec-
trometry (MS/MS) enhances dramatically their structural elu-
cidation, for example, individual triacylglycerols. Besides,
GC–MS is also used to analyze free fatty acids and triacylgly-
cerols, although it required derivatization procedures (e.g.,
transformation of free fatty acids in the methyl esters).
Carbohydrate
Carbohydrates, the most abundant natural products, can be
classified according to their degree of polymerization (DP).
They can be divided initially into three principal groups, namely,
simple sugars (DP 1–2), oligosaccharides (DP 3–9), and
polysaccharides (DP > 9). They are one of the most important
components for nutrition and health, because they have impor-
tant physiological role. They can serve as structural elements in
plants (as cellulose), important sources of dietary fiber, and
major sources of energy (as starch or glucose) in food. For the
reasons mentioned earlier, carbohydrates are specially targeted
via HPLC–MS or GC–MS methods in food. Monosaccharides
and small oligosaccharides have been traditionally analyzed via
GC–MS. However, the use of derivative reaction in GC–MS
method hampered its application to larger oligosaccharides
and molecular conjugates. Due to the high polarity and low
volatility of carbohydrates, ESI ionization is usually preferred
over APCI ionization. Carbohydrates can be hardly observed in
negative ionization, due to its lower sensitivity, while they can be
sensitive in the positive ionization mode. For example, the addi-
tion of Li salts with low concentration to the HPLC eluents
produces [M þ Li]þ ions and can increase the sensitivity of
carbohydrate compounds in food.
Carotenoids
Carotenoids are lipid-soluble pigments responsible for the color
of a wide variety of fruits and vegetables. Some of them are
provitamin A carotenoids, subsequently transformed into vita-
min A, which can prevent serious eye diseases, such as night
blindness; susceptibility to infection; rough, scaly skin; and
retarded tooth and bone development. There are about 700
carotenoids in nature, but only about 50 have provitamin activ-
ities. Of those 50 compounds, the three most important pre-
cursors of vitamin A in humans are a-carotene, b-cryptoxanthin,
and b-carotene.
A range of LC-based techniques have been used to analyze
carotenoids, most of them coupled to a PDA or UV–vis detec-
tor. Although LC separation coupled to UV–vis instruments
has been the most common analytic method for determining
carotenoids qualitatively and quantitatively, the spectra of
many carotenoids are very similar, so many researchers
have complemented the identification of carotenoids using
other detectors, such as MS. With UV and PDA systems, it is
impossible to provide molecular structure information for
identification, especially for unknown carotenoids in complex
sample matrices. The MS instruments are used to overcome
spectral interferences in UV–vis and, therefore, to achieve
high sensitivity in complex mixtures and to obtain molecular
structure information on the basis of the molecular mass and
fragmentation pattern under tandem MS (MS/MS and MS/
MS/MS).
82 Chromatography: Combined Chromatography and Mass Spectrometry
For HPLC–MS, usually ESI, sometimes APCI ionization, is
used. There are many examples of analysis and quantitation of
vitamins in food via HPLC–MS. Most carotenoids are apolar
compounds, so APCI (possibly also APPI) ionization may be
more advantageous than the more commonly used ESI.
HPLC–MS/MS has also been used to distinguish between
structurally related molecules and their epoxidized forms, prod-
ucts of carotenoid oxidation, that are potential oxidative stress
markers and difficult to profile due to their small amounts and
the difficulty in separating them from hydroxyl carotenoids.
Amino Acids, Peptides, and Proteins
There is currently a general trend in food science towards the
consideration of food as an affordable way to prevent diseases. In
this sense, one of the main challenges is to improve our limited
understanding on the interaction of food compounds with genes
and their subsequent effect on proteins and metabolites; this
knowledge should allow a rational design of strategies to manip-
ulate cell functions through diet, which is expected to have an
extraordinary impact on our health in the nondistant future.
Proteomics is the large-scale analysis of a proteome that
includes all the expressed proteins in a particular biological
system at a given time, whereas peptidomics is the analysis of
all peptide content within an organism, tissue, or cell (pepti-
dome) including not only the peptide present in the system but
also the transient products of protein degradation. In general,
the major difficulty in the analysis of protein and peptides
comes from the different physicochemical properties of pro-
teins, the high number of peptidic sequences that can become
available, and the huge dynamic concentration range of both
families of compounds in real samples. Proteomics and pepti-
domics offer multiple applications in food science including
food processing, food quality, food safety, and characterization
of healthy food ingredients.
LC–MS has been extensively used in the identification and
determination of amino acids, peptides, and proteins. In earli-
est studies, for example, conventional RP-HPLC with chiral
derivatization agents was used for the determination of
amino acids. However, these methods were not applicable in
real food samples because of the insufficient sensitivity and the
interference from the numerous coexisting amino acids. For
the determination of peptides and proteins, HPLC–MS plays a
critical role. By using RP-HPLC, ion exchange, hydrophobic
interaction chromatography, etc., peptides and proteins can be
separated via the differences in surface hydrophobicity or
surface charge. These methods provide the practical technolo-
gies to separate complex food matrices, and the affinity
chromatography allows the purification of targeted peptides
and proteins. After HPLC separation, most peptides and pro-
teins in the low concentration range can be identified by MS
techniques.
CE-MS has been mainly applied for proteomics,
peptidomics, and metabolomics studies. Capillary electropho-
resis techniques coupled to MS are ideal analytic techniques for
different ‘omics’ approaches such as metabolomics, proteo-
mics, and peptidomics mainly due to the particular character-
istics of this separation technique. CE provides fast and highly
efficient separations, low reagent and sample consumptions
(CE is particularly well suited for samples that are volume-
limited), and high versatility considering the different CE
modes available. The main drawback of CE is its poor
sensitivity, but it can be improved by combining CE with MS
detection, while the use of preconcentration strategies can give
further sensitivity gain. Besides, the use of MS as detector pro-
vides additional selectivity and structural information of the
detected compounds.
Polyphenols
Flavonoids are polyphenolic compounds, usually found in
food and beverage. The motivation of flavonoids analysis
using HPLC–MS or GC–MS methods arises from their
potential beneficial effects on human health. Flavonoids are
usually present in low amounts in a complex matrix of plant
extracts and thus generally are difficult to isolate in higher
quantities. This, combined with their good sensitivity in elec-
trospray, makes HPLC–MS the method of choice for flavonoid
analysis. To increase selectivity (often a critical aspect) and
high mass resolution and to increase structural information,
tandem mass spectrometry is often used in HPLC–MS analysis
of flavonoids.
In the other side, several CE-ESI-MS methods have been
developed for the analysis of flavonoids, using high-pH run-
ning buffers containing ammonium acetate and MS detection
in the negative-ion mode. Other natural compounds bearing
phenol structures have been analyzed by CE-MS. Thus, a com-
parison between HPLC-ESI-MS and CE-ESI-MS for the analysis
of phenolic compounds from red wines showed that in spite of
CE providing much higher separation efficiency than HPLC, 24
compounds could be identified by HPLC–MS vs. 13 com-
pounds identified by CE-MS in the mentioned red wine
extracts.
Food additives
Food additives are strictly limited; only additives explicitly
authorized may be used in food. Monitoring foodstuffs for
additives is an area of increasing concern and importance.
Due to its excellent figures of merit, HPLC–MS is often a
method of choice. Food additives are groups of substances
commonly classified according to their application and not
to their chemical structure. Some of these are small molecules
(like benzoic acid used for conservation), some are macromol-
ecules (like the ‘infamous’ guar gum, causing concern a few
years ago), some are synthetic products, while others are
natural extracts. For these reasons, it is difficult to generalize
the ‘proper’ analytic method to be used for their characteriza-
tion. Some methods are compound-specific (and do not
estimate total amount of a given class of compounds); some
characterize groups of substances. Often, both identification
and quantification are required. Generic procedures for the
simultaneous extraction of various classes of food additives
and residues in various matrices are in use.
Analyzing Hazardous Food Components via
Chromatography–MS
Mycotoxin
Mycotoxins are toxic secondary metabolites of fungi (usually
molds) that readily colonize crops or foodstuffs during storage.
Most often, these are present in cereals and oil seeds. A
 Chromatography: Combined Chromatography and Mass Spectrometry
database reported 474 mycotoxins and fungal metabolites,
while previously unknown metabolites have recently been
created. These toxins are dangerous even in very small
amounts. Therefore, for some mycotoxins, maximum residue
level of aflatoxins B1, for example, as low as 0.1mgkg1 has
been established by the EU for baby foods and processed
cereal-based foods for infants and young children (please see
EC No 1881/2006). For mycotoxin analysis, two different
strategies can be followed to develop and validate analytic
methods. One is to set up a screening method to detect and
roughly quantify as many metabolites as possible, reducing the
selectivity in extraction and cleanup steps. The other approach
is to develop a high-performance method to accurately quan-
titate a few selected mycotoxins in selected cases. For both
approaches, a number of methods have been developed and
validated by diverse research groups. The combination of
HPLC with MS/MS has proved to be a powerful tool for the
simultaneous determination of different classes of mycotoxins.
Besides mycotoxins, also their metabolites often formed in
plants and animals might be hazardous for man. Such conju-
gated or masked mycotoxins can also be analyzed with
LC–MS/MS methods, very well suited for high sample through-
put, and should be included into multimycotoxin analysis for
the direct detection and characterization of metabolites in
complex biological and food matrices.
Mycotoxin analysis uses a variety of mass spectrometric
methods. Electrospray (in both positive-ion mode and
negative-ion mode), APCI, and APPI ionizations are all fre-
quently used. Triple-quadrupole instruments are often used
for targeted analysis, while high-resolution analysis is used to
look for unexpected derivatives. When quantitation is needed,
using isotope-labeled standards, whenever available, is highly
advantageous for accurate and precise analysis.
Pesticide residues
Pesticide residues in food are a growing concern, both for the
consumers and for legislation. Widespread use of pesticides
necessitates their trace analysis in vegetables and various food
products. There are several hundred active ingredients and
thousands of formulations currently in use. Like in the case
of mycotoxins, a large number of compounds need to be
screened and, if found, accurately quantified. Simultaneous
analysis of pesticides requires development of efficient high-
throughput methods.
A significant fraction of pesticide trace analysis is based on
HPLC–MS. In most cases, tandem mass spectrometry is uti-
lized, as it allows simplification of sample treatment prior to
the analysis and achieves multiresidue analysis in a single
chromatographic run. When quantitation is needed, using
isotope-labeled standards, whenever available, is highly advan-
tageous for accurate and precise analysis.
For chromatography, often, UHPLC (ultrahigh-performance
liquid chromatography) is used. UHPLC allows fast and effi-
cient separation and analysis is usually performed in less than
15 min chromatograms. For analysis, most often, a C18 column
with small particle size (1.7 m) is used. The most often used
mass spectrometer is the triple quadrupole (QqQ) that achieves
tandem mass spectrometry. The QqQ literally has three quadru-
pole mass analyzers in the same instrument. The first analyzer is
set to transmit the precursor (usually the molecular) ion; in the
83
central quadrupole, collision-induced dissociation (CID) takes
place, while the second analyzer transmits the expected product
ion, which is detected. In this instrument, several precursor
ion ! product ion transitions are selected (selected reaction
monitoring (SRM)) to increase sensitivity.
Increasing selectivity is of prime importance for analyzing
trace components in complex materials. For this reason, con-
ventional selected ion monitoring (SIM) in a single quadru-
pole is usually not considered sufficiently selective to identify
pesticide traces in food. Besides tandem mass spectrometry,
analysis using high mass resolution (HRMS) is another direc-
tion to increase selectivity. This can be carried out using
time-of-flight (TOF), Orbitrap, or Fourier transform (FT)
mass spectrometers.
A further option to increase accuracy and reliability of
pesticide analysis is the use of isotope dilution (that means to
use the isotopically labeled analyte as internal standard). This
enhances accuracy of analysis and at the same time may allow a
simplified sample preparation process. However, it increases
the costs of analysis significantly, so for this reason, it is rarely
used for routine pesticide analysis in the agrifood sector.
Pesticide analysis is one of the most important applications
in the agrifood sector. A large variety of different foodstuffs are
routinely analyzed, including baby food, vegetables, vegetable
oil, honey, fruit juice, wine, and milk.
Conclusion
In the past years, there has been an emerging investigation for the
food safety and food quality analysis using chromatography–MS
methods, including HPLC, GC, and CE. These combined
methods allow the rapid, reliable, and accurate analysis,
identification, and quantification in food matrices. State-of-the-
art MS instruments enhanced analytic sensitivities for the identi-
fication of trace components of food and provide a powerful tool
for analyzing various foods to meet the requirements of food
legislation or the concerns about toxicity. Combined MS
(LC–MS, GC–MS, etc.) and MS/MS methods can reduce the
time and labor-consuming sample preparation processes and
improve the selectivity for both qualitative and quantitative ana-
lyses of food samples present in complex matrices. The advances
of simple, robust, and reliable portable chromatography–MS
method can promise an on-site, rapid, accurate identification
and quantification of unknown compounds in food.
See also: Chromatography: Focus on Multidimensional GC;
Chromatography: High-Performance Liquid Chromatography; Food
Poisoning: Tracing Origins and Testing; HACCP and ISO22000: Risk
Assessment in Conjunction with Other Food Safety Tools Such as
FMEA, Ishikawa Diagrams and Pareto.
Further Reading
Agrawal GK, Sarkar A, Righetti PG, et al. (2013) A decade of plant proteomics and mass
spectrometry: translation of technical advancements to food security and safety
issues. Mass Spectrometry Reviews 32: 335–365.
84 Chromatography: Combined Chromatography and Mass Spectrometry

Arena S, Salzano AM, Renzone G, Dambrosio C, and Scaloni A (2014) Non-enzymatic Mohamed R and Guy PA (2011) The pivotal role of mass spectrometry in determining
glycation and glycoxidation protein products in foods and diseases: an the presence of chemical contaminants in food raw materials. Mass Spectrometry
interconnected, complex scenario fully open to innovative proteomic studies. Mass Reviews 30: 1073–1095.
Spectrometry Reviews 33: 49–77. Sandrin TR, Goldstein JE, and Schumaker S (2013) MALDI TOF MS profiling
Botitsi HV, Garbis SD, Economou A, and Tsipi DF (2011) Current mass spectrometry of bacteria at the strain level: a review. Mass Spectrometry Reviews 32: 188–217.
strategies for the analysis of pesticides and their metabolites in food and water Wang J (2009) Analysis of macrolide antibiotics, using liquid chromatography-mass
matrices. Mass Spectrometry Reviews 30: 907–939. spectrometry, in food, biological and environmental matrices. Mass Spectrometry
Garcia-Canas V, Simo C, Leon C, Ibanez E, and Cifuentes A (2011) MS-based analytical Reviews 28: 50–92.
methodologies to characterize genetically modified crops. Mass Spectrometry
Reviews 30: 396–416.
Hernandez F, Portoles T, Pitarch E, and Lopez FJ (2011) Gas chromatography coupled
to high-resolution time-of-flight mass spectrometry to analyze trace-level organic
compounds in the environment, food safety and toxicology. Trac-Trends In Relevant Websites
Analytical Chemistry 30: 388–400.
Herrero M, Simo C, Garcia-Canas V, Ibanez E, and Cifuentes A (2012) Foodomics: MS- http://www.asms.org/ – AAMS.
based strategies in modern food science and nutrition. Mass Spectrometry Reviews http://www.bmss.org.uk/index.html – BMSS.
31(1): 49–69. http://www.bmb.leeds.ac.uk/esms/ – ESMS.
Li P, Zhang Z, Hu X, and Zhang Q (2013) Advanced hyphenated chromatographic-mass http://www.imss.ie/index.htm – IMSS.
spectrometry in mycotoxin determination: current status and prospects. Mass http://www.chem.purdue.edu/cooks/MS%20Links.htm – Mass Spectrometry Links.
Spectrometry Reviews 32: 420–452. http://www.saams.up.ac.za/ – SAAMS.
Malik AK, Blasco C, and Pico Y (2010) Liquid chromatography-mass spectrometry in http://www.ualberta.ca/gjones/mslib.htm – Mass Spectrometry Database, American
food safety. Journal of Chromatography A 1217: 4018–4040. Academy of Forensic sciences.