QuEChERS Method

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Recent Advances and

Developments in the
QuEChERS Method
Bárbara Socas-Rodrı́guez, Javier González-Sálamo,
Antonio V. Herrera-Herrera, Javier Hernández-Borges and
Miguel Á. Rodrı́guez-Delgado1
Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Spain
1
Corresponding author: E-mail: mrguez@ull.edu.es
Chapter Outline
1. Introduction 2 3. Application Fields 13
2. Modifications of the Original 3.1 Pesticide Analysis 13
Method 8 3.2 Pharmaceutical Analysis 20
2.1 pH Adjustment 8 3.3 Mycotoxin Analysis 25
2.2 Extraction Solvent 10 3.4 Polycyclic Aromatic
2.3 Dispersive Solid-Phase Hydrocarbon Analysis 31
Extraction Sorbents 10 3.5 Miscellaneous 37
2.4 Salt Addition 11 4. Conclusions and Future Trends 43
2.5 Freezing of the Sample or Acknowledgements 44
Introduction of a Freezing- References 44
Out Step 12
Glossary CEN European Committee for

Standardization.
ACN Acetonitrile. CLC Capillary liquid chromatography.
Al-N Alumina neutral. DAD Diode array detector.
AOAC Association of Analytical DART Direct analysis in real time.
Communities. DCM Dichloromethane.
ASE Accelerated solvent extraction. di-Na Sodium citrate dibasic
BSA Bis-(trimethylsilyl)acetamide. sesquihydrate.
C18 Octadecylsilane. DLLME Dispersive liquideliquid
CCa Limit of decision. microextraction.
CCb Detection capability. d-SPE Dispersive solid-phase
CE Capillary electrophoresis. extraction.
Comprehensive Analytical Chemistry, Vol. 76. http://dx.doi.org/10.1016/bs.coac.2017.01.008

Copyright © 2017 Elsevier B.V. All rights reserved. 1
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2 Comprehensive Analytical Chemistry
ECD Electron capture detector. OCP Organochlorine pesticide.

EN European norm. OH-PAH Monohydroxylated poly-
EPA Environmental Protection cyclic aromatic hydrocarbon.
Agency. PAH Polycyclic aromatic hydrocarbon.
EtOAc Ethyl acetate. PBDE Polybrominated diphenyl ether.
EU European Union. PBS Phosphate-buffered saline.
EURL European Union Reference PCB Polychlorinated biphenyl.
Laboratories. PFC Perflourinated compound.
FA Fatty acid. PLE Pressurized liquid extraction.
FD Fluorescence detector. PSA N-propylethylendiamine.
FIA Flow injection analysis. Q Single quadrupole.
FID Flame ionization detector. QAC Quaternary ammonium
GAC Green analytical chemistry. compound.
GC Gas chromatography. QqQ Triple quadrupole.
GCB Graphitized carbon black. QTOF Quadrupole-time of flight.
HLB Hydrophilicelipophilic balance. RSD Relative standard deviation.
HPLC High-performance liquid SAX Strong anion exchange.
chromatography. SFE Supercritical fluid extraction.
IAC Immunoaffinity column. SFO Solidification of floating organic
IL Ionic liquid. drop.
IS Internal standard. SLE Solideliquid extraction.
LC Liquid chromatography. SPE Solid-phase extraction.
LLE Liquideliquid extraction. SVHC Substance of very high concern.
LOD Limit of detection. TFA Trifluoroacetic acid.
LPGC Low-pressure gas TMCS Trimethylchlorosilane.
chromatography. TMSI N-trimethylsilylimidazole.
MeOH Methanol. TOF Time of flight.
MRL Maximum residue limit. TPP Triphenylphosphate.
MS Mass spectrometry. tri-Na Sodium citrate tribasic
MSPD Matrix solid-phase dispersion. dihydrate.
MWCNT Multiwalled carbon TSL Terbium-sensitized luminescence.
nanotube. UAE Ultrasound-assisted extraction.
Na2EDTA Disodium UFLC Ultra-fast-liquid
ethylenediaminetetraacetate. chromatography.
NaOAc Sodium acetate. UHPLC Ultra-high-performance
NH4OAc Ammonium acetate. liquid chromatography.
NPD Nitrogen phosphorus detector. UV Ultraviolet.
1. INTRODUCTION
The term ‘green chemistry’ emerged from the increasing concern for the
development of chemical products and processes that reduce or eliminate the
use or generation of hazardous substances. It has its roots in the Federal
Pollution Prevention Act of 1990 of the US Senate [1]. The main objective of
green chemistry is the prevention of pollution at the molecular level in all
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Advances and Developments in the QuEChERS Method Chapter j 3
disciplines of chemistry and the application of innovative scientific solutions

to environmental problems [1]. Thus, the design of chemical products and
processes with reduced intrinsic hazards to both human’s health and the
environment is a priority topic. Initially, green chemistry was obviously
orientated to organic synthetic procedures. However, this concept was
subsequently adapted to other fields of chemistry, including analytical
chemistry, as also shown in chapter: Green Analytical Chemistry: The Role of
Green Extraction Techniques by Armenta et al. [1a] of this book.
Green analytical chemistry (GAC) could be defined, under the principles of
green chemistry, as the discipline responsible for the development of cleaner or
more ecofriendly methodologies (elimination or minimization of pollutants) to
determine low concentration of analytes in samples with a complex matrix
composition without compromising accuracy, sensitivity, and reproducibility
[2,3]. Apart from the environmental advantages, the application of green chem-
istry principles in analytical chemistry allows reducing the cost of the analysis,
improves the speed of methodologies, and increases the safety for operators [3].
The different steps of the whole analytical process (i.e., sample collection
and storage, sample preparation, analysis and data processing) are susceptible to
being modified with the aim of reducing environmental pollution [2,4]. How-
ever, sample preparation is one of the most contaminant steps of any analytical
procedure due to the consumption of solvents and other chemical substances
used to remove matrix interferences and to concentrate the target compounds.
Thus, it is not surprising that a great number of authors have focused their
research on this stage of the methodology, as can be seen in the numerous
review articles published [2,3,5,6]. From such point of view, the so-called
QuEChERS method (standing for quick, easy, cheap, effective, rugged, and safe)
has emerged as a greener alternative to traditional sample preparation steps.
The QuEChERS method was introduced in 2003 by Michelangelo Anas-
tassiades (visiting scientist from Chemisches und Veterinäruntersuchungsamt,
Stuttgart, Germany), Steven J. Lehotay (US Department of Agriculture,

Philadelphia, Pennsylvania, USA), Darinka Stajnbaher (Public Health Institute,
Maribor, Slovenia), and Frank J. Schenck (U.S. Food and Drug Administration,
Atlanta, Georgia, USA) [7] as an alternative method to extract pesticide residues
in vegetables and fruits. It consists of two different steps: (1) a solideliquid
extraction/partitioning with a salting out effect and (2) a dispersive solid-phase
extraction (d-SPE) for sample cleanup purposes. Despite the fact that both steps
had been extensively used in the analysis of a wide variety of compounds in
different complex matrices, this methodology was a genuine revolution in the
analysis of contaminants and residues. This fact is clearly demonstrated by
the enormous number of articles and reviews devoted to almost all types of
compounds and samples published since then [8e12], although many articles
claim to have used the whole method when only one of the steps has been used
[11,13]. Apart from this, the transcendence of the method is such that two of its
versions are nowadays official methods of analysis of international standard
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organizations (the European Union [14] and AOAC International [15]) to

determine residues of pesticides in fruit and vegetables.
The importance of the method lies in the ingenious combination of
procedures, solvents, salts and sorbents to provide suitable results in a very
effective way with a reduced cost in a relatively short time. In fact, authors
already affirmed in the original article that six chopped samples could be
prepared in less than 30 min by a single analyst with a cost lower than 1 US
$/sample and this fact was later demonstrated.
The original intent of the authors was to introduce not only a more
ecofriendly methodology but also a more efficient extraction method. Until
that date, different multiclass multiresidue methods had been widely used.
However, such methods did not cover the increasing demands of the agrifood
industry and health monitoring programs. The authors made an intensive,
systematized, and thorough study of the different factors affecting the effi-
ciency of the two extraction steps: sample size and comminution, sample
composition (pH and amount of matrix constituents), type of solvents used,
sample/solvent ratio, agitation mode (blending or shaking), temperature,
addition of a cosolvent and/or salts, extraction time, and cleanup sorbent. It is
worth noting that the final conditions were selected as a situation of
compromise to maximize simplicity, applicability, speed, selectivity, and
recovery of the analytes. For this purpose, the amount of coextracted material,
the amount of water and colouration of the extract, recovery, matrix back-
ground in mass spectrometry (MS) chromatograms and matrix-induced chro-
matographic effects were taken into consideration.
In their first article [7], the authors initially studied sample size and
comminution. As it was well known, the analytical efficiency of a particular
method can be improved (in terms of solvent volume, safety concerns, storage,
time and cost) by reducing the sample to the minimum homogeneous amount
that provides reliable results. It is important to note that such griding must
provide representative samples with intact integrity (no pesticide losses).
Previously developed multiclass multiresidue methods used sample amounts
between 50 and 100 g unless other extraction techniques [such as supercritical
fluid extraction, matrix solid-phase dispersion (MSPD) or pressurized liquid
extraction (PLE)] were used, in which case 5e15 g were considered enough.
In their case, based on previous experience and evidence in the literature, the
authors selected 10 g as a representative sample. They also recommended an
exhaustive comminution to maximize surface area and to ensure better contact
since a blender was not used during extraction as well as the use of dry ice to
avoid pesticide losses.
Regarding the extraction solvents, nonpolar and chlorinated substances
[petroleum ether, dichloromethane (DCM), etc.] or polar solvents [acetone,
acetonitrile (ACN) and ethyl acetate (EtOAc)] had been traditionally used in
multiclass multiresidue methods to extract pesticides. Taking into account
their intrinsic handicaps (petroleum ether and DCM are highly toxic, acetone
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and ACN are difficult to separate from water and EtOAc has a reduced affinity
for highly polar pesticides [7]), acetone, ACN and EtOAc were initially
selected since they had previously shown to offer high recovery for a
reasonable range of pesticides. These three solvents were compared in
experiments in which the rest of the parameters were maintained constant. The
authors found that ACN coextracted less material from fruits and vegetables
than acetone and EtOAc after d-SPE with N-propylethylendiamine (PSA) and
also less amounts than the other two solvents without using such cleanup step
(Fig. 1). Moreover, ACN can be separated from an aqueous phase by adding
salts (unlike acetone which needs a nonpolar cosolvent), does not extract a
high amount of lipophilic material, can be used with nonpolar solvents to
introduce an additional cleanup (if needed), and has a lower volatility
(compared with acetone and EtOAc). Moreover, the residual water in ACN can
be removed by drying agents (such as MgSO4) and this solvent is compatible
with both gas chromatography (GC) and liquid chromatography (LC) appli-
cations. For these reasons, such solvent was chosen for further experiments.
Solvent-to-sample ratio was also found to be fundamental to
guarantee effective extraction of all pesticides. Due to the high water content
of fruits and vegetables (80%e95%), the proportion 1/1 of sample/ACN
provides higher water content than that previously found as ideal to extract
nonpolar pesticides [16]. In such case, the intimate contact between both
solvents makes ACN much stronger for their extraction. Thus this ratio was
selected, which clearly reduces the amount of organic solvent used.
Concerning the agitation method, the authors compared shaking versus
blending for the initial extraction. Shaking was found acceptable even for
without PSA Cleanup with PSA SPE Cleanup

3.5
Co-Extracted Matrix (mg/g)
2.8
2.1
1.4
0.7
0
EtOAc ACN ACN:Acetone Acetone
Extraction Solvent
FIGURE 1 Comparison of different solvents for the extraction of a mixture of fruits and vege-
tables with and without d-SPE cleanup step using PSA as sorbent. The y-axis represents the
coextracted matrix amount (mg) dissolved in the final extract per gram of the original sample
amount extracted. ACN:acetone ratio was 1/1. ACN, acetonitrile; d-SPE, dispersive solid-phase
extraction; PSA, N-propylethylendiamine. Redrawn from M. Anastassiades, S.J. Lehotay,
D.
Stajnbaher, F.J. Schenck, Fast and easy multiresidue method employing acetonitrile extraction/
partitioning and “dispersive solid-phase extraction” for the determination of pesticide residues in
produce, J. AOAC Int. 86 (2003) 412e431 with permission of AOAC International.
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incurred residues that might not be easily accessible for extraction. Thus,
bearing in mind these results and other possible advantages of shaking over
blending (sample not exposed to the active surface of the blender, no cleaning
of the blender is needed between samples, more samples can be extracted in
parallel and no frictional heat is generated), a vortex mixer was used.
According to previously published methods, the introduction of a salt to
induce phase separation by means of a salting out effect appeared to be
appropriate to improve recovery values [17e19]. On the one hand, the
introduction of a salt usually increased recovery of polar pesticides and
controlled the percentage of water in the organic phase. On the other hand,
such introduction avoided the use of a cosolvent with its associated disad-
vantages (dilution and inadequate polarity of the extracts). Fructose, MgCl2,
NaNO3, Na2SO4, LiCl, MgSO4 and NaCl were tested with this objective in the
first application of the method. Among them, MgSO4 provided the best results
because it demonstrated to bind large amounts of water and thus to promote
partitioning of analytes in the ACN layer. However, strong agitation should be
applied just after the addition of MgSO4 to avoid the formation of conglom-
erates. The exotherm of the hydration of MgSO4 (40e45 C) was also found to
be of benefit to the extraction, especially for nonpolar pesticides. Moreover,
the combination or substitution of MgSO4 with NaCl was evaluated, obtaining
satisfactory results. In terms of recovery, MgSO4 alone provided higher values
than using only NaCl. However, and regarding selectivity, NaCl addition
reduced partitioning of polar matrix compounds into the organic phase, which
was not expected. Furthermore, NaCl had a great positive influence on the
peak shape and areas of different pesticides, which is why NaCl was also
included in the extraction step, but its concentration was carefully optimized to
achieve a compromise between both opposite effects.
Another important factor that was also studied in the first publication of the
QuEChERS method was the pH of the sample, since some pesticides degrade
rapidly at high pH values and others are poorly recovered at low pH. The pH
values of fruits and vegetables tend to be in the acidic range (in the range
2.5e6.5) but authors hypothesized that pH would not have a significant effect
on their method since an important amount of water remains in the ACN phase
after separation. Several experiments demonstrated that acid conditions have a
negligible effect even for the most basic pesticides. This effect was found
important using other extractant solvents such as EtOAc. However, to ensure a
quantitative recovery of alkaline-sensitive pesticide, it was necessary to adjust
the pH of various vegetables below 4. Apart from that, it is not surprising that
pH could also have a strong influence on the coextraction of matrix in-
terferences. As can be seen in Fig. 2, the coextraction of fatty and other acids
increased at lower pH values. It is important to mention that recovery of
alkaline-sensitive pesticides is also affected by the acidity of the final extracts.
These kinds of pesticides could be lost during sample extraction with pH
values higher than 5 and also after the d-SPE cleanup with PSA (which
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FIGURE 2 Effect of pH on the presence of matrix coextractives in GCeMS chromatograms (full

scan mode) of ACN apple juice extracts obtained using 1 g NaCl and 5 g MgSO4 to induce
partitioning. ACN, acetonitrile; GC, gas chromatography; MS, mass spectrometry. Reprinted from
M. Anastassiades, S.J. Lehotay, D. Stajnbaher, F.J. Schenck, Fast and easy multiresidue method
employing acetonitrile extraction/partitioning and “dispersive solid-phase extraction” for the
determination of pesticide residues in produce, J. AOAC Int. 86 (2003) 412e431 with permission
of AOAC International.
contains primary and secondary amines that also affect the pH). Authors
demonstrated that pesticides were stable for more than a day in ACN extracts
when 0.05%e0.1% (v/v) acetic acid was added. Although they avoided the use
of any acid, these observations provided suitable evidence for the current use
of the buffered QuEChERS methods, which are indeed current official
methods [14,15] as it will be later shown.
It should be remarked that the ACN phase obtained was water dried and
cleaned up simultaneously. Drying was necessary since water can affect both
the d-SPE and GC determination. In this sense, MgSO4 was preferred over
Na2SO4 as drying agent because it removed water more effectively and
provided less polar extracts causing precipitation of certain polar interferences
of the matrix. Regarding the d-SPE sorbent, the authors tested PSA, a meth-
acrylate-divinylbenzene copolymeric sorbent, graphitized carbon black
(GCB), alumina neutral (Al-N), a strong anion exchanger (SAX), as well as
cyanopropyl, aminopropyl and octadecylsilane (C18). Among them, the
mixture of PSA and GCB removed the high amount of matrix materials in the
ACN phase. However, GCB was found to retain certain pesticides due to its
high affinity towards planar molecules. Other sorbent combinations did not
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provide an additional cleanup. As a result, PSA was initially selected as

cleanup sorbent.
Finally, authors carried out the quantification by using matrix-matched
calibration, that is, standards added to blank extracts before and after the
d-SPE step e without differences in the results e as well as non-matrix-
matched calibration, which used standards added to solutions of analyte
protectants. The use of analyte protectants was tested with the aim of
providing an alternative tool to correct matrix effect for laboratories that
cannot use matrix-matched calibration. Thus, compounds with multiple
hydroxyl, amino and/or carboxyl groups capable of forming hydrogen bonds
were tested as analyte protectants. None of the tested substances was effective
for all the analytes but a combination of sorbitol and 3-O-ethylglycerol proved
to be useful. Moreover, triphenylphosphate (TPP) was used as an internal
standard (IS) to eliminate the sources of inherent errors of the method (the IS
was added after the first partitioning step).
To sum up, the original QuEChERS method consisted of the extraction of
10 g of chopped and homogenized sample with 10 mL of ACN. After vigorous
shaking for 1 min by vortex, 4 g of MgSO4 and 1 g of NaCl were added and
the mixture was immediately vortexed 1 min more (to avoid formation of
conglomerates). Then, the IS was added, the mixture was vortexed for 30 s and
centrifuged for 5 min at 5000 rpm. An aliquot of 1 mL of the ACN phase was
then mixed with 25 mg of PSA and 150 mg of MgSO4. The mixture obtained
was vortexed for 30 s, centrifuged for 1 min at 6000 rpm and 0.5 mL was
transferred to a vial and analysed by GCeMS. It is worth mentioning that
authors highlighted the need for further research to apply the method to LC (or
faster chromatographic methods) and fatty matrices as well as to use large-
volume injections.
2. MODIFICATIONS OF THE ORIGINAL METHOD

Despite the fact that the original QuEChERS method has shown excellent
efficiency for the extraction of hundreds of analytes from a wide variety of
matrices, since its creation, some modifications have been proposed from the
need of obtaining high recovery, of avoiding pesticide degradation and
diminishing matrix effects. Such new amendments (Fig. 3) have allowed
improving the performance of the original QuEChERS method even more,
especially when complex matrices are analysed. These modifications maintain
both liquideliquid extraction (LLE) and d-SPE steps but have modified the
solvents, salts and sorbents originally used in each of them.
2.1 pH Adjustment
As it is well known, there are certain pH-dependent analytes that undergo
ionization and/or even degradation processes depending on the pH of the
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Anastassiades et al., 2003 Original

QuEChERS
Quick method
Easy
Cheap
Effective 10 g sample Water addition
extraction with (samples with water
Rugged 10 mL ACN content < 80%)
Safe
Sample
Formate buffer Citrate buffer 4 g MgSO4 and Acetate buffer freezing
and others (EN 15662) 1 g NaCl (AOAC 2007.01) (thermolabile
analytes)
Others: d-SPE:
Use of C18 and
Florisil®, 1 mL extract, Additional
Use of GCB Z-Sep or Z-
MWCNTs, 150 mg MgSO4
Zep+ freeze-out step
Chlorofiltr®, etc. and 25 mg PSA
Analysis
FIGURE 3 Schematic summary of the original QuEChERS method and its most relevant
modifications.
matrix. If any of these facts take place, analytes may not pass to the organic
layer or may degrade during the initial LLE step, resulting in low recovery. For
this reason, most efforts have been focused on the development of pH-
controlled extraction/partitioning steps.
Regarding the previously mentioned aspects, two official methods were
proposed from the original unbuffered version [7] trying to extend the method
to these analytes. The first one was proposed by Lehotay and co-workers and
makes use of an acetate buffer at high concentration to achieve a greater
buffering strength (AOAC Official Method 2007.01 [15]). However, part of the
buffer that also partitions into the organic phase results in an ACN constant pH
and the strong buffer capacity of acetate produced a visibly worse cleanup with
PSA with respect to the original method [20]. The second version was
developed by Anastassiades and co-workers and consists in the addition of a
citrate buffer that provides a lower buffering capacity [European Committee
for Standardization (CEN) Standard Method EN 15,662 [14]] and has no
negative effects in the PSA cleanup. Both buffered methods provide a pH
around 5 allowing the satisfactory extraction of pesticides, which are sensitive
under acidic or basic conditions (e.g., folpet, dichlofluanid, pymetrozine,
chlorothalonil) independently of the fruit/vegetable matrix. However, and
despite the fact that both versions have been used as routine methods in many
laboratories thanks to their inherent advantages, buffering is not recommended
for certain matrices (i.e., those with a high lipid content) due to the reduction
of PSA retention capacity at such pH, as it has just been commented [21],
resulting in higher amount of coextractives.
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Despite the fact that these QuEChERS versions were originally thought
for the analysis of pesticides, they have also been applied to the extraction of
a wide variety of analytes with a different nature [22e24]. Moreover, other
buffers that have also been used are formate [25,26] (with a particular aspect
that will be later described in Section 2.4) or phosphate-buffered saline
(PBS), although, in this last case, for the analysis of other compounds like
mycotoxins [22].
Finally, it has to be mentioned that another typical problem related with
pH-dependent pesticide degradation takes place at the end of the process, since
the final extracts normally have a measured pH of around 8e9, which leads to
base-sensitive pesticide degradation [10,20]. This problem can be overcome by
the addition of 5% (v/v) formic acid in ACN, obtaining a final pH about 5,
although it is especially relevant when samples are stored for a certain time
before injection. Thus, a short time between sample treatment and injection
can also avoid this fact [10,27].
2.2 Extraction Solvent

Many times, the features of the samples that are going to be analysed deter-
mine the solvents that have to be used. Thus, one of the simplest proposed
modifications has been the addition of a certain volume of water (in addition to
the extraction solvent) at the beginning of the process [28,29], making possible
to extend the methodology to the analysis of commodities with less than 80%
of water content (i.e., cereals, flours, etc.). Water allows weakening in-
teractions between analytes and matrix ensuring a suitable partitioning in the
first step.
Beside this, a suitable selection of the organic solvent is crucial to guar-
antee that the target analytes are extracted from the aqueous matrix. In this
sense, ACN has been occasionally replaced by other organic solvents like
acetone [30] or n-hexane [31]. Mixtures of solvents, such as ACN:methanol
(MeOH) [32,33], ACN:n-hexane [34] or DCM:hexane [35] have also been
applied. In many of such cases, the same salts (MgSO4 and NaCl) were added.
2.3 Dispersive Solid-Phase Extraction Sorbents

Apart from avoiding analyte ionization and/or degradation during the LLE
procedure, many efforts have also been made to reduce the amount of coex-
tractive compounds, which can later interfere in the correct determination of
the analytes. For this purpose, other sorbents different from PSA have been
proposed as part of the d-SPE cleanup step for the selective removal of certain
coextractives.
In this regard, there are two main modifications that could be considered as
part of the current universal QuEChERS method aimed to obtain cleaner
extracts prior to the analysis. The first implied the use of different amounts of
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PSA [21,36] or its combination with C18 [23,29,37,38]. Contrary to PSA, C18
does not produce a decrease in pesticide recovery and is particularly useful
when matrices with high lipid content (e.g., cereals, avocado or milk) are
analysed. For these reasons, some modified methods have only used C18 to
remove fats avoiding the use of PSA [39e41]. The second is the combination
of PSA with GCB, which allows the successful removal of planar pigment
coextractives from coloured matrices, obtaining less coloured extracts [28,42],
although, as previously mentioned, it can also retain planar analytes. In the
specific case of planar pesticides, it has been demonstrated to decrease the
recovery by up to 25% [43,44].
Although the use of C18 and GCB with or without PSA may be considered
as an essential part of the current QuEChERS method, there are many other
sorbents that can also be considered in the d-SPE cleanup step. In this sense,
new materials based on zirconium oxide have already been used for
lipid removal [45e48] and are providing interesting results in different fields.
These kinds of sorbents have shown to be more efficient than PSA and C18 for
both fat and pigment removal, providing higher recovery values. Nowadays, it is
possible to find two zirconium-based materials commercially available called Z-
Sep and Z-Sepþ. The first is a combination of Si coated with ZrO2, while the
second also has C18 in a 2:5 ratio. Regarding pigment removal, ChloroFiltr,
which is a polymer-based sorbent, has emerged as an important alternative to
the use of GCB [49], since it provides a selective reduction of chlorophyll
content in the final extract without loss of planar analytes. Furthermore, other
new cleanup sorbents have also been employed, including alumina (for lipo-
philic compounds elimination) [50], Florisil (magnesium silicate e for the
separation of nonpolar or low polar analytes) [31,51e53], nanomaterials like
multiwalled carbon nanotubes (MWCNTs) [54] or even magnetic nanoparticles
[55e57] thanks to their high surface area and high extraction capacity. Some
other interesting alternative materials have been successfully applied as cleanup
sorbents, including diatomaceous earth [58], SAX (a strong anion exchange
sorbent based on trimethylaminopropyl-functionalized silica particles) [59] or
polymer-based sorbents such as styrene-divinylbenzene [60], although it is true
that these materials have not been widely used.
Finally, it should be mentioned that some other versions have emerged in
which the d-SPE procedure has been replaced by a conventional SPE step
[61e63]. However, and despite the fact that SPE columns tend to give a
greater cleaning power, the procedure itself cannot achieve the same level of
simplicity and speed of the d-SPE, the reason why d-SPE continues to be the
procedure mostly used [44].
2.4 Salt Addition

As previously mentioned, the initial LLE step requires the addition of NaCl to
favour the salting out effect as well as the addition of MgSO4 to eliminate
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water to dry the organic layer. However, it should be taken into account that
these salts could also affect the instrumentation used for the subsequent
determination.
In this sense, González-Curbelo et al. have proposed an interesting
alternative using ammonium chloride and ammonium formate and acetate
buffers for the extraction of representative pesticides [25,26]. As it is well
known, MgSO4 and NaCl tend to deposit as solids in some parts of the
instrumentation used after QuEChERS (GCeMS or LCeMS), which leads
to a loss in the instrumentation performance. The use of ammonium salts
avoids this problem and enhances the formation of analyte ions, while
formate buffer ensures a suitable pH during the extraction step indepen-
dently of the matrix. Although the performance of the three methods
compared favourably with QuEChERS in the AOAC Official Method [15],
the use of the formate buffer [7.5 g of ammonium formate and 15 mL of 5%
(v/v) formic acid in ACN for the extraction of 15 g of fruit/vegetable sam-
ples] ensured a suitable pH for high recovery of most pesticides indepen-
dently of the matrix.
Concerning salt addition during the d-SPE cleanup, it has also been
proposed to change MgSO4 by CaCl2 since it improved water removal and
fortified the interactions between matrix components and PSA resulting in a
better purification [64]. However, this alternative is conditioned by the absence
of polar pesticides since CaCl2 produces an important decrease in the recovery
of such analytes [27,64].
2.5 Freezing of the Sample or Introduction of a Freezing-Out

Step
The temperature during the QuEChERS process may also affect the perfor-
mance of the method. In this sense, the exothermic hydration reaction that
takes place after the addition of anhydrous MgSO4 to the sample is well known
and may degrade thermally labile analytes [44]. To reduce this problem,
freezing the sample before the initial extraction [65,66] or adding cold water to
it (<4 C) if water addition is needed [67] have been proposed as alternatives,
the first one being the most suitable due to the soft temperatures reached after
extraction.
Low temperatures have also been used before and after the d-SPE step in
the so-called freeze-out step, which leads to lipid precipitation [36,68,69].
This step does not need additional sorbents but implies the freezing of the
extract for 1e2 h, which results in a clear increase of the sample treatment
time [69], although this time can be reduced by employing dry ice baths
[68]. Moreover, it has been demonstrated that such step is in fact unnec-
essary in pesticide analysis if the d-SPE procedure is developed with PSA
and C18 [70].
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3. APPLICATION FIELDS
3.1 Pesticide Analysis
As it is widely known, pesticides constitute a group of contaminants of special
concern. They are extensively applied in modern agriculture to protect crops
from different diseases, weeds or insects [29]. However, they can denote
significant health risks to consumers due to their persistence after the harvest
step, appearing in agricultural and processed food products as well as other
environmental matrices related to this field [10,29]. For this reason, it is of
high importance that the analytical methodologies used for their determination
allow the analysis of a wide number of compounds with good recovery values
using, ideally, a fast and simple procedure. In this sense, the QuEChERS
method has resulted to be an excellent alternative for this purpose able to
provide enough sensitivity to reach the low maximum residue limits (MRLs)
established for these contaminants in different matrices by several interna-
tional organizations. In fact, nowadays more than 650 pesticides and their
metabolites are included in the European Union Reference Laboratories
(EURL) DataPool database for the validation of their data using this meth-
odology [8,71].
As it has been previously reviewed [9,11,72], pesticides constitute the
main application field of the QuEChERS method, not only for fruit and
vegetables as it was originally applied but also for other wide variety of
matrices including other foods of different nature, environmental samples
and even biological fluids or nonedible plants. In Table 1, some of the
published articles in this field have been summarized. As can be seen, both
the original and modified versions of the method have been applied for the
extraction of different groups of pesticides, although multiresidue analyses
have also been extensively carried out [29,31,52,54,76e78,81e83]. As an
example, Lozowicka et al. [83] developed a QuEChERS approach to analyse
400 pesticides in sugar beet and beet molasses using a citrate buffer in the
extraction step as well as PSA and GCB as cleanup sorbents prior to their
determination by GCeMS/MS and high-performance liquid chromatography
(HPLC)eMS/MS. Good results with limits of detection (LODs) in the range
5e10 mg/kg and recovery values between 60% and 140%, which allows the
application of the methodology as routine-multiresidue method [85], were
obtained.
As previously mentioned, a common tendency, also in this field, is the
introduction of alternative cleanup sorbents such as Florisil [31,52,53], zir-
conium-based sorbents [47,48] or even MWCNTs [54,86,87] to increase the
recovery efficiencies and matrix cleanness. In this sense, Volpatto et al. [53]
tested the extraction of 19 different pesticides from grapes using the con-
ventional and the acetate-buffered methods resulting that the last approach
provided better and more consistent recovery for the selected pesticides than
TABLE 1 Some Examples of the Application of the QuEChERS Method to the Analysis of Pesticides
Extraction
Sample Sorbents in the Analytical Recovery
Analytes (Amount) Solvents Salts d-SPE Step Method (%) LODs Comments References
58 Pesticides Soil (5 g) 10 mL ACN 4 g MgSO4, 900 mg GCeMS/MS 69e119 0.03e1.5 10 mL of water was [29]
1% acetic 1 g NaCl MgSO4, mg/kg added initially. Real
acid (v/v) 150 mg PSA, samples were
150 mg C18 analysed. Different
cleanup sorbents
were tested.
Heptachlor epoxide
was
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used as IS
8 Pyrethroid Green and red 20 mL ACN 2 g NaCl 150 mg PSA, GCeECD 79e104 1.2e150 10 mL of water was [73]
pesticides pepper (10 g), 1% acetic 50 mg C18 mg/kg added initially for
dehydrated red acid (v/v), dehydrated red
pepper (1 g) 2 mL hexane pepper. Real
samples were
analysed
11 OCPs Beans, 10 mL ACN 3 g MgSO4, 1.5 g MgSO4, GCeECD 80e92 0.25e19.29 GCxGC-TOF-MS [74]
cabbage, beef, 1.5 g NaCl 27.5 mg PSA mg/kg was used to confirm
fish (10 g) the identification of
target compounds
in samples. Real
samples were
analysed
11 Pesticides Coconut pulp 10 mL ACN 4 g MgSO4, 600 mg UHPLCeMS/ 70e120 3 mg/kg Cooling of [75]
(10 g), coconut 1% acetic 1.5 g MgSO4, MS supernatant in a dry
water (10 mL) acid (v/v) NaOAc 100 mg PSA, ice prior to the
500 mg C18 cleanup step
88 Pesticides Human milk 1 mL ACN 0.4 g 157 mg GCeMS/MS 70e120 0.2e2 mg/kg Freezing of [76]
(1 mL) 1% acetic MgSO4, MgSO4, 9 mg supernatant at
acid (v/v) 0.1 g PSA, 9 mg C18 20 C for 2 h prior
NaOAc to cleanup step TPP
was used as IS
120 Pesticides Apple, 10 mL ACN 4 g MgSO4, 900 mg HPLCeMS/ 70e120 1.2e100 e [77]
cucumber 1 g NaCl, MgSO4, MS mg/kg
(10 g) 0.5 g di-Na, 150 mg PSA
1 g tri-Na
21 Pesticides Olive and 20 mL ACN 8 g MgSO4, 0.5e3.5 g Z- HPLCeDAD 50e130 e 10 mL of water was [47]
grapeseed oil 2 g NaCl Sep added initially.
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(6 g) An additional
SPE step using
C18 cartridges was
carried out before
d-SPE
4 Pesticides Maize grain 10 mL ACN 4 g MgSO4, 200 mg UHPLCeMS/ 80e110 1.8 mg/kg 2 mL of water was [41]
(5 g), maize 1% acetic 1 g NaCl MgSO4, 25 mg MS added initially
straw (2 g), soil acid (v/v) C18
(5 g)
74 Pesticides Orange juice 10 mL ACN 4 g MgSO4, 150 mg UHPLCeMS/ 70e118 3.0e7.6 mg/ TPP was used as IS [78]
(10 mL) 1% acetic 1.7 g MgSO4, 40 mg MS kg
acid (v/v) NaOAc PSA
116 Pesticides Honey (5 g) 10 mL 4 g MgSO4, 150 mg UHPLCeMS/ 70e120 5 mg/kg 10 mL of water was [52]
ACN:EtOAc 1 g NaOAc MgSO4, 50 mg MS added initially
70/30 (v/v) PSA, 50 mg
1% acetic Florisil
acid (v/v)
Continued
TABLE 1 Some Examples of the Application of the QuEChERS Method to the Analysis of Pesticidesdcont’d
Extraction
24 Pesticides Fruit, cereal, 15 mL ACN 6 g MgSO4, 150 mg GCeMS 70e120 10e50 mg/ Comparison of d- [79]
starch and milk 1% acetic 1.5 g MgSO4, 50 mg kg SPE cleanup step
baby food acid (v/v) NaOAc PSA, 50 mg C18 with DLLME. TPP
(15 g) was used as IS
28 Carbamate Aromatic herb 10 mL ACN 4 g MgSO4, 200 mg UHPLCeMS/ 72e99 0.6 mg/kg Comparison with [80]
pesticides (1 g) 1 g NaCl MgSO4, MS other d-SPE sorbents
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200 mg C18
30 Pesticides Milk (20 mL) 16 mL ACN 8 g MgSO4, 125 mg PSA, HPLCeDAD 70e100 0.02e0.06 - [48]
2 g NaCl 25 mg Z-Sep, (for mg/L
5 mg Z-Sepþ almost all
pesticides)
74 Pesticides Medicinal plant 20 mL hexane 2 g NaCl, 50 mg MgSO4, GCeMS/MS 70e120 3 mg/kg 10 mL was added [31]
(2 g) 3 g NaOAc 50 mg C18, initially.
50 mg Florisil Chlorpyrifos-d10
was used as IS
223 Pesticides Tobacco (2 g) 20 mL ACN 4 g MgSO4, 150 mg GCemECD/ 71e120 1e1.2 mg/kg 2 mL of water was [81]
1 g NaCl, MgSO4, 25 mg NPD added initially.
0.5 g di-Na, PSA, 2.5 mg Comparison with
1 g tri-Na GCB MSPD and SLE
methods. GCeMS/
MS was applied for
confirmation
studies. TPP was
used as IS
66 Pesticides Grape (10 g) 10 mL ACN 4 g MgSO4, 300 mg UHPLCeMS/ 70e120 3 mg/kg TPP was used as IS [82]
1% acetic 1.7 g MgSO4, MS
acid (v/v) NaOAc 100 mg PSA
171 Pesticides Cowpea (10 g) 10 mL ACN 4 g MgSO4, 150 mg GCeMS/MS 74e129 1e3 mg/kg Comparison with [54]
1 g NaCl MgSO4, 5 mg (for PSA and C18
MWCNTs almost all cleanup sorbents
pesticides)
400 Pesticides Sugar beet, beet 10 mL ACN 4 g MgSO4, 150 mg GCeMS/MS, 60e140 5e10 mg/kg 5 mL of water was [83]
molasses (10 g) 1% formic 1 g NaCl, MgSO4, 25 mg HPLCeMS/ added initially for
acid (v/v) 0.5 g di-Na, PSA, 2.5 mg MS beet molasses
1 g tri-Na GCB samples. Freezing of
supernatant at
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60 C for 30 min
prior to cleanup
step. TPP was used
as IS for GCeMS/
MS and atrazine-d5
carbendazim-d3
and isoproturon-d6
for HPLCeMS/MS.
Comparison with
MSPD and
conventional
QuEChERS methods
13 OCPs Fish (5 g) 10 mL ACN 4 g MgSO4, 50 mg PSA GCeECD 88e121 0.65e1.58 DLLMEeSFO was [84]
1 g NaCl mg/kg integrated in the
cleanup step to
concentrate de
extract
Continued
TABLE 1 Some Examples of the Application of the QuEChERS Method to the Analysis of Pesticidesdcont’d
Extraction
19 Pesticides Grape (10 g) 10 mL ACN 4 g MgSO4, 300 mg GCeMS 95e102 6e12 mg/kg Comparison with [53]
1% acetic 1 g NaOAc MgSO4, conventional
acid (v/v) 400 mg Florisil QuEChERS.
Quintozene and
caffeine were used
as ISs of method
and instrumental,
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respectively.
ACN, acetonitrile; C18, octadecylsilane; DAD, diode array detector; di-Na, sodium citrate dibasic sesquihydrate; DLLME, dispersive liquideliquid microextraction; d-SPE, dispersive solid-
phase extraction; ECD, electron capture detector; GC, gas chromatography; GCB, graphitized carbon black; HPLC, high-performance liquid chromatography; IS, internal standard; LOD, limit
of detection; MS, mass spectrometry; MSPD, matrix solid-phase dispersion; MWCNT, multiwalled carbon nanotube; NaOAc, sodium acetate; NPD, nitrogen phosphorus detector; OCP,
organochlorine pesticide; PSA N-propylethylendiamine; SFO, solidification of floating organic drop; SLE, solideliquid extraction; TOF, time of flight; TPP, triphenylphosphate; tri-Na, sodium
citrate tribasic dihydrate; UHPLC, ultra-high-performance chromatography.
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the conventional one, including problematic pesticides with pH dependency

such as cyprodinil, myclobutanil and tebuconazol. In the same way, different
cleanup sorbents including GCB, C18, PSA and Florisil were evaluated indi-
cating that Florisil also provided an adequate removal of pigments, similar to
the ones obtained with PSA, but a higher number of pesticides with recovery
in the range 70%e120% were extracted. Thus, a Florisil cleanup step was
applied together with a buffered acetate extraction prior to the analysis by
GCeMS for the determination of the 19 pesticides with recovery values of
95%e102% and low LODs (in the range 6e12 mg/kg).
Another important aspect that could be seen in the literature is the
combination of QuEChERS with other methodologies with the aim of
improving the results obtained. As an example, Wang et al. [84] combined
dispersive liquideliquid microextractionesolidification of floating organic
droplet (DLLMEeSFO) with the d-SPE cleanup step of the QuEChERS method
using 50 mg of PSA after previous extraction with 10 mL of ACN as well as 4 g
of MgSO4 and 1 g of NaCl for the analysis of 13 organochlorine pesticides from
catfish samples. The DLLMEeSFO, which was carried out using ACN as
dispersant and 1-undecanol as extraction solvent and by the addition of 6 mL of
water to favour the transference of the analytes to the organic layer, provided a
considerable increase of the enrichment factor improving the sensitivity of the
technique. Besides, in this approach, the organic layer was solidified in an ice
bath simplifying its collection and avoiding its losses during the process. As a
result, excellent recovery in the range 88%e121% with relative standard
deviations below 15% and very low LODs (0.65e1.58 mg/kg) were obtained.
Other examples of this type can be found in [88,89].
With respect to the analytical methods used for the analysis of pesticides in
combination with QuEChERS, the coupling of LC [41,52,75,78,80,82,83] and
GC [29,31,53,54,76,79,83] with MS is the technique most commonly used as
well as low-pressure GC [25] and GCxGC [69], simple quadrupole and triple
quadrupole being the analysers mostly employed. However, the combination
of LC with other detectors as, for example, diode array detector (DAD)
[47,48], and the coupling of GC with an electron capture detector [73,74,84] or
a nitrogen phosphorus detector [81] as well as other separation techniques such
as capillary electrophoresis (CE) have been used in several studies [90,91]. In
the case of CE, the technique has not been so widely applied as LC or GC and
the first published works were somehow delayed, probably due to the inade-
quate conductivity of the final extract that may preclude the injection in the CE
system, even though it has been demonstrated that CE can also be used for this
purpose.
Regarding the use of ISs, although TPP was proposed and applied with success
by Anastassiades et al. in their first work (also in a higher number of occasions
[76,79,82,83]), isotopic labelling of target pesticides is a common practice
[25,31,70,83,92]. However, others like heptachlor epoxide [29], 4-bromo-3,5-
dimethylphenyl-N-methylcarbamate [93], 4,40 -dichlorobenzophenone [94],
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diazinon [95], ethoprophos [96] or quintozene [53] have been occasionally used
for specific groups of pesticides.
3.2 Pharmaceutical Analysis

Pharmaceuticals are compounds administrated to humans and animals to
prevent or treat different diseases. However, the presence of these analytes as
contaminants is mainly associated with their use in animal feeding, veterinary
treatments and growth promotion. Consequently, they can appear in animal
products, edible tissues and environmental matrices, exposing humans to
different negative side effects [33] such as haematological, gastrointestinal and
neurological diseases [97]; muscular tremors; cardiac palpitations; nervous-
ness, headache or muscular pain [98], among others. Due to all these aspects,
different regulations have been ascertained to control them. As an example, the
European Union has established MRLs in the range 0.12e20,000 mg/kg for
pharmacologically active substances in foodstuffs of animal origin [99].
Taking these data into account, the necessity of developing convenient ap-
proaches as the QuEChERS method presents great relevance, especially in
environmental and food safety fields.
As is shown in Table 2, the applications of QuEChERS to the analysis of
pharmaceuticals have focused not only on the determination of specific
groups, for example, alkaloids [28], nonsteroidal compounds [40], acyl urea
derivatives [23], polyether carboxylic acids [51], b-agonists and b-blockers
[98,102], sulphonamides [45], heterocyclic amines [34], macrocyclic lactones
[101], benzodiazepines [103] or phenylpropanoids [46], but also in multi-
residue analyses [32,33,100]. Among them can be found pharmaceuticals used
for the specific treatment of glycaemia, hypotension, hypocholesterolaemic
and hypoglycaemic regulators [28] as well as anti-inflammatory [40], anti-
parasitic [23,101], antimicrobial [51], growth promoter [98,102], antibacterial
[45,46,97], anti-infective [34] or sedatives drugs [103].
There also exist a large number of modified versions of QuEChERS that
have been applied for the analysis of pharmaceuticals because of the great
variety of compounds used for this purpose and the different nature of the
studied matrices. Among them can be found a wide variety of environmental
(i.e., poultry litter [51] and pork manure [32]) or food samples (i.e., vegetables
[33], cereals [28], milk [40,46], honey and royal jelly [46,100], mollusc [23],
fish [103], poultry, porcine and bovine edible tissues [34,45,97,98,101], animal
feed [102] or eggs [45]).
Regarding the extraction step, pH adjustment with different acids such as
acetic [40,97,98], formic [28,45,46], ascorbic [40] or citric acid [100]; buffers
[23,28,40,45,97,101,102,104]; or bases [105,106] have been widely applied.
With respect to the cleanup step, C18 and PSA have been the sorbents most
commonly applied both together and separately, but other interesting sorbents
such as Florisil [51] or Z-Sepþ [45,46] have been introduced for the study of
TABLE 2 Some Examples of the Application of the QuEChERS Method to the Analysis of Pharmaceuticals
Extraction Sorbents in
Sample the d-SPE Analytical Recovery
Analytes (Amount) Solvents Salts Step Method (%) LODs Comments References
Atropine, Buckwheat, 10 mL ACN 4 g MgSO4, 25 mg PSA, UHPLCeMS/ 50e92 0.04e0.2 mg/kg 10 mL of [28]
scopolamine wheat, soy, 1% formic 1 g NH4OAc 25 mg GCB MS water was
buckwheat acid (v/v) added initially
flour,
buckwheat
noodle,
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amaranth
grain, chia
seeds,
peeled
millet (5 g)
10 Nonsteroidal Milk (5 g) 10 mL ACN 1 g NH4OAc, 1 g MgSO4, HPLCeMS/ 78e97 CCa: 6 mL of water [40]
anti- 5% acetic 5 g Na2SO4 150 mg C18 MS 0.4e1.5 mg/kg, was added
inflammatory acid (v/v), 4 mL CCb: initially.
drugs ascorbic acid 0.8e1.9 mg/kg Meloxicam-d3,
0.02 M, HCl niflumic acid-
0.24 M 13 C , flufenamic
6
acid-13 C6 and
phenylbutazone-
13 C
12 were
used as ISs.
Comparison
between QqQ and
Q-Orbitrap
MS was used
Continued
TABLE 2 Some Examples of the Application of the QuEChERS Method to the Analysis of Pharmaceuticalsdcont’d
Diflubenzuron Mussel 10 mL ACN 4 g MgSO4, 900 mg HPLCeDAD 101 30 mg/kg Study of the [23]
(10 g) 1 g NaCl, MgSO4, half-life of
0.5 g di-Na, 150 mg PSA, diflubenzuron
1 g tri-Na 150 mg C18 in mussel
w10 mg/kg
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3 Ionophore Poultry 10 mL ACN 4 g MgSO4, 150 mg HPLCe 70e120 10 mL of water [51]
antimicrobials litter (5 g) 1 g NaCl MgSO4, 25 mg MS/MS was added
Florisil initially. Real
samples were
analysed.
Nigericin was
used as IS
14 b-Agonists, 2 Porcine 10 mL ACN 3 g MgSO4, 150 mg C18 UHPLCeMS 67e121 0.17e1.67 mg/ 2 mL of water [98]
b-blockers muscle 1% acetic 0.5 g NaCl kg was added
(3 g) acid (v/v) initially. Real
samples were
analysed
22 Sulfonamides Chicken, 10 mL ACN 4 g MgSO4, 900 mg LCeMS/MS e e 2 mL of water [97]

beef and 1% acetic 1 g NaCl, MgSO4, was added
sheep acid (v/v) 0.5 g di-Na, 150 mg PSA initially.
meat (5 g) 1 g tri-Na Sulfamethoxazole-
d4 was used as IS
90 Veterinary Royal 5 mL citric acid 2 g NaCl, 2 g 200 mg NH2 UHPLCeMS/ 70e120 0.07e6 mg/kg Real samples [100]
drugs jelly (1 g) 0.1 M:Na2HPO4 Na2SO4 sorbents MS were analysed
0.2 M 8/5 (v/v),
20 mL ACN 5%
acetic acid (v/v)
Methenamine Pork muscle, 10 mL ACN, 4 g Na2SO4 50 mg PSA HPLCeMS/ 87e110 1.5 mg/kg Methenamine- [34]
liver and 5 mL hexane MS 13 C 15 N was
6 4
kidney used as IS
tissues (2 g)
Abamectin, Bovine liver 10 mL ACN 4 g MgSO4, 1 g MgSO4, HPLCeFD 85e90 CCa: Analytes were [101]
ivermectin, (10 g) 1 g NaCl, 25 mg PSA, 23e127 mg/kg derivatized to be
doramectin, 0.5 g di-Na, 200 mg C18 analysed by FD
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moxidectin 1 g tri-Na
Ractopamine Pork 10 mL ACN 4 g MgSO4, 900 mg HPLCeMS/ 96e107 1.91 mg/kg Sample was [102]
feed (5 g) 1 g of NaCl, MgSO4, MS previously
0.5 g di-Na, 150 mg PSA, hydrolysed using a
1 g tri-Na 150 mg C18 protease and
b-glucuronidase
enzyme.
Isoxsuprine
hydrochloride
was used as IS
26 Veterinary Pork 20 mL 4 g MgSO4, 40 mg PSA, HPLCeMS/ 61e106 0.01e Comparison of [32]

drugs manure MeOH:ACN:0.1 1 g NaCl 20 mg C18 MS 1.86 mg/kg d-SPE step with
(2 g) M EDTA conventional HLB
McIlvaine cartridges
Buffer
12.5/37.5/50
(v/v/v)
Continued
TABLE 2 Some Examples of the Application of the QuEChERS Method to the Analysis of Pharmaceuticalsdcont’d
8 Sulfonamides Chicken 10 mL ACN 4 g MgSO4, Muscle: HPLCeFD 66e81 4.2e25.5 mg/kg e [45]
muscle and 1% acetic 1 g NaOAc 300 mg Z-
egg (5 g) acid (v/v) Sepþ, egg:
300 mg PSA
Diazepam, Carp (2 g) 10 mL ACN 2 g MgSO4, 100 mg PSA HPLCeMS/ 89e110 0.5 mg/kg Comparison with [103]
nordiazepam, 1 g NaCl MS MWCNTs as
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temazepam, d-SPE sorbent
oxazepam
3 Veterinary Milk, 15 mL ACN 0.1% 4 g MgSO4, 900 mg CLCeMS/MS 96e100 0.02e0.045 mg/ e [46]
antibiotics honey (2 g) acetic 1 g NaCl Na2SO4, kg
acid (v/v) 500 mg C18,
500 mg Z-
Sepþ
11 Celery, 7 mL Na2EDTA 2 g Na2SO4, 225 mg HPLCe 70e119 0.7e8 mg/kg Comparison with [33]
Pharmaceuticals lettuce 150 mg/ 0.5 g NaCl Na2SO4, MS/MS ASE and UAE
(500 mg) L:ACN:MeOH 12.5 mg PSA, methods
28.6/46.4/25.0 12.5 mg C18
(v/v/v)
ACN, acetonitrile; ASE, accelerated solvent extraction; C18, octadecylsilane; CCa, limit of decision; CCb, detection capability; CLC, capillary liquid chromatography; DAD, diode array detector;
di-Na, sodium citrate dibasic sesquihydrate; d-SPE, dispersive solid-phase extraction; EDTA, ethylenediaminetetraacetate; FD, fluorescence detector; HLB, hydrophilicelipophilic balance; HPLC,
high-performance liquid chromatography; IS, internal standard; LOD, limit of detection; MeOH, methanol; MS, mass spectrometry; MWCNT, multiwalled carbon nanotube; NaOAc, sodium
acetate; NH4OAC, ammonium acetate; PSA, N-propylethylendiamine; Q, Single quadrupole; QqQ, triple quadrupole; tri-Na, sodium citrate tribasic dihydrate; UAE, ultrasound-assisted extraction;
UHPLC, ultra-high-performance liquid chromatography.
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pharmaceuticals. Besides, the d-SPE step was also compared with other
conventional cleanup procedures [32]. With this aim, Guo et al. [32] evaluated
the application of 40 mg of PSA and 20 mg of C18 as cleanup sorbents
of pork manure extracts for the analysis of 26 veterinary drugs by
QuEChERS-HPLCeMS/MS and compared the results obtained with
hydrophilicelipophilic balance (HLB) SPE cartridges. Besides, the use of
HLB cartridges involved a higher consumption of time, and, as can be seen in
Fig. 4, d-SPE provided higher recovery values than conventional HLB SPE
as well as a smaller range of variability (4.4%e15%) than the one obtained
for commercially cartridges, which ranged between 3.3% and 21.2%.
Apart from the comparison with other cleanup approaches, the whole
method has also been compared with alternative methodologies. In this sense,
Chuang et al. [33] evaluated the extraction of 11 pharmaceuticals from celery
and lettuce using 7 mL of a mixture of Na2EDTA, ACN and MeOH together
with 2 g of Na2SO4 and 0.5 g of NaCl followed by a cleanup step with 225 mg
of Na2SO4, 12.5 mg of PSA and 12.5 mg of C18, prior to their analysis by
HPLCeMS/MS and their comparison with accelerated solvent extraction
(ASE) and ultrasound-assisted extraction (UAE). While UAE provided re-
covery values lower than 40% for some of the analytes, ASE and QuEChERS
methods resulted in acceptable recovery, higher than 70%. However, the
QuEChERS method seems to be easier and less solvent- and time-consuming
than the rest of the approaches applied, achieving an overall recovery in the
range 70%e119% and LODs of 0.7e8 mg/kg.
Regarding the combination of the QuEChERS method with different
analytical techniques for the analysis of pharmaceuticals, the most common
choice is, as it is well known, LCeMS/MS, HPLC [32e34,40,51,102,103] or
ultra-high-performance liquid chromatography (UHPLC) [28,100]. However,
other techniques such as GC (less common) [107], capillary LC [46] or even
direct analysis in real time (DART), which does not require a previous chro-
matographic separation [106], have also provided adequate results.
3.3 Mycotoxin Analysis

Mycotoxins are secondary metabolites of diverse fungal species and are
mainly produced during the process of growing, harvesting, transformation
and storage of crops [22]. They are considered important contaminants since
they can be toxic and produce a large number of diseases in humans and
animals including hormonal disorders, immunosuppression or the teratogenic,
mutagenic and even carcinogenic activities [108].
As it has been previously reviewed [9,10,109], the application of the
QuEChERS method for the extraction of mycotoxins has been almost exclu-
sively focused in the analysis of food matrices such as cereals
[37,39,110e114], milk [115], vegetables [42], eggs [108], fruits [67], drinks
[116] or other food plants [117] since food is the most direct route for human
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FIGURE 4 Comparison of recovery values obtained by the d-SPE approach and the traditional HLB SPE for the analysis of 26 different veterinary drugs including
sulfonamides, macrolides and fluoroquinolones from pork manure. d-SPE, dispersive solid-phase extraction; HLB, hydrophilicelipophilic balance. Reprinted from
C. Guo, M. Wang, H. Xiao, B. Huai, F. Wang, G. Pan, X. Liao, Y. Liu, Development of a modified QuEChERS method for the determinationof veterinary antibiotics
in swine manure by liquid chromatography tandem mass spectrometry, J. Chromatogr. B 1027 (2016) 110e118 with permission of Elsevier.
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exposure. However, as it is shown in Table 3, in which the applications

of QuEChERS for the extraction of this group of analytes are presented, other
matrices like medicinal plants [22], earthworms [118] or dietary supplements
[119] have also been studied in a few occasions. In this sense, Veprikova et al.
[119] analysed 57 mycotoxins in plant-based dietary supplements intended
for different purposes including liver diseases, reduction of menopause
effects and general health support. The extraction was carried out using 10 mL
of 1% (v/v) acetic acid, 10 mL of ACN, 4 g of MgSO4 and 1 g of NaCl,
followed by a cleanup step using 300 mg of MgSO4 and 100 mg of C18 prior to
the determination by UHPLCeMS/MS. Results showed recovery values in the
range 40%e122% and LODs between 1.5 and 300 mg/kg.
The addition of acid additives and citrate salts in the first step of the
method has been widely applied in this case [9,23,28,40,97,98,100e102], but
other salts have also been included to increase the efficiency of the extraction.
In this sense, Michlig et al. [115] added 1 mL of Na2EDTA 1 M to 10 mL of
ACN with formic acid 0.1% (v/v), with the aim to favour the extraction of
aflatoxin M1 from 10 mL of milk obtaining excellent results. Aflatoxin M1
was protein bonded and the addition of Na2EDTA allows breaking casein
micelles. With a similar goal, Xing et al. [22] used 5 mL of PBS together with
2.5 mL of ACN with acetic acid 5% (v/v) to establish an adequate pH and
acuo-organic ratio, which allowed extracting 21 mycotoxins with very
different hydrophobicity from a Chinese herb, obtaining excellent recovery
values (between 75% and 104%).
Regarding the cleanup step, PSA and C18 are, once more, the sorbents
mostly used [22,37,39,67,108,110,115,116,119], but others, for example, Al-N
for cereal samples [113] or GCB for medicinal animals [118], vegetables [42]
or food plants samples [117], have also been included in a few occasions with
excellent results. Besides, several studies have also been developed to compare
the effectiveness of d-SPE with that of other cleanup procedures [110,115].
Pereira et al. [110] compared the extraction of 12 mycotoxins from cereal baby
foods using a cleanup step with PSA as sorbent with the application of
MultiSep cleanup columns and immunoaffinity columns (IAC) prior to their
determination by GCeMS. Results showed that contrary to d-SPE, IAC cannot
be applied for the analysis of a great variety of mycotoxins due to their
specificity, since it was only possible to extract 3 of 12 compounds with this
procedure. With respect to MultiSep cleanup columns, which are mixtures of
sorbents especially designed for mycotoxin analysis, recovery values were
acceptable for almost all analytes (21%e103%) but the methodology was
more complex, expensive and time-consuming.
Concerning the separation techniques, GCeMS [110,116] and specially
LCeMS/MS [22,37,39,42,108,115,117e119] are the most commonly used,
although for the first one, derivatization of the analytes with bis-(trimethylsilyl)
acetamide/trimethylchlorosilane/N-trimethylsilylimidazole was necessary in
some cases. Besides, although less common, others such as LCeDAD [67], flow
TABLE 3 Some Examples of the Application of the QuEChERS Method to the Analysis of Mycotoxins
21 Mycotoxins Chinese herb 5 mL PBS, 2 g MgSO4, 150 mg UHPLCeMS/MS 75e104 0.031e5.4 Study of different [22]
(1 g) 2.5 mL ACN 0.5 g NaCl, MgSO4, mg/kg cleanup sorbents.
5% acetic 0.5 g tri-Na, 150 mg C18 Real samples were
acid (v/v) 0.25 g di-Na analysed
Patulin Wheat tortilla 10 mL ACN 4 g MgSO4, 1.2 g MgSO4, HPLCeMS/MS e 0.2 mg/kg e [37]
(10 g) 1 g NaCl 400 mg PSA,
400 mg C18
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22 Mycotoxins Medicinal 15 mL ACN 4 g MgSO4, 900 mg UHPLCeMS/MS 73e105 0.05e10 Before cleanup [118]
earthworm 15% formic 1 g NaCl MgSO4, mg/kg step, sample was
(1 g) acid (v/v) 300 mg PSA, placed in an ice
900 mg C18, bath for 10 min.
60 mg GCB Atrazine-d5
and13C-
zearalenone were
used as ISs
Aflatoxin M1 Defatted and 10 mL ACN 4 g MgSO4, 200 mg UHPLCeMS/MS 70e95 0.002 mg/L Comparison with [115]
whole milk 0.1% formic 1 g NaOAc MgSO4, IAC cleanup
(10 mL) acid (v/v), 67 mg PSA,
1 mL 180 mg C18
Na2EDTA
1M
7 Mycotoxins Egg (2 g) 10 mL ACN 4 g MgSO4, 100 mg PSA, UHPLCeMS/MS 85e115 1e5 mg/kg 2 mL of water was [108]
0.1% formic 1 g NaCl 100 mg C18 added initially
acid (v/v) Real samples were
analysed
9 Mycotoxins Beet (6 g) 5 mL formic 4 g MgSO4, 150 mg HPLCeMS/MS 64e168 e Real samples were [42]
acid 0.1% 1 g NaCl, MgSO4, (21 and 34 analysed
(v/v), 10 mL 1 g tri-Na, 25 mg PSA, for gliotoxin
ACN 0.1% 0.5 g di-Na 7.5 mg GCB and
formic acid roquefortine
(v/v) C)
10 Mycotoxins Wheat, 15 mL ACN 5.5 g 2 g MgSO4, HPLCeMS/MS 87e106 0.062e199 10 mL of water [39]
maize, rice 1% acetic MgSO4, 1.4 337 mg C18 mg/kg was added
(7.5 g) acid (v/v) NaCl, 1 g initially. Real
tri-Na, 0.5 g samples were
di-Na analysed
14 Mycotoxins Beer (10 mL) 5 mL ACN 4 g MgSO4, 900 mg GCeMS/MS 70e110 0.05e8 mg/L Analytes were [116]
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1 NaCl MgSO4, derivatized to be
300 mg C18 analysed by
GCeMS/MS. Real
samples were
analysed
3 Mycotoxins Pomegranate 15 mL ACN 4 g MgSO4, 600 mg HPLCeDAD 82e108 15e20 e [67]

fruit (2 g) and 1% acetic 1 NaCl MgSO4, mg/kg
juice (2 mL) acid (v/v), 200 mg PSA
7 mL cold
water
12 Mycotoxins Cereal baby 10 mL ACN 4 g MgSO4, 1.350 g GCeMS 44e135 0.37e19.19 15 mL of water [110]
food (2.5 g) 1 NaCl MgSO4, mg/kg was added
450 mg PSA initially.
a-Chloralose
and 13 C15 -
deoxynivalenol
was used as IS
Comparison with
MultiSep cleanup
columns and IAC
Continued
TABLE 3 Some Examples of the Application of the QuEChERS Method to the Analysis of Mycotoxinsdcont’d
3 Mycotoxins Strawberry 10 mL ACN 6 g MgSO4, 855 mg UHPLCeQTOF- 55e106 0.6e0.96 10 mL of water [117]
plant (10 g), 1 g NaCl, MgSO4, MS mg/kg was added
maize plant 1 g tri-Na, 150 mg PSA, initially.
(5 g) 0.5 g di-Na 45 mg GCB Roxithromycin 4
was used as IS.
57 Mycotoxins Plant-based 10 mL formic 4 g MgSO4, 300 mg UHPLCeMS/MS 40e122 1.5e300 mg/ e [119]
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dietary acid 1% (v/v), 1 g NaCl MgSO4, kg
supplement 10 mL ACN 100 mg C18
(1 g)
ACN, acetonitrile; C18, octadecylsilane; DAD, diode array detector; di-Na, sodium citrate dibasic sesquihydrate; d-SPE, dispersive solid-phase extraction; GC, gas chromatography; GCB,
graphitized carbon black; HPLC, high-performance liquid chromatography; IAC, immunoaffinity column; IS, internal standard; LOD, limit of detection; MS, mass spectrometry; NaOAc, sodium
acetate; PBS, phosphate-buffered saline; PSA, N-propylethylendiamine; QTOF, quadrupole-time of flight; tri-Na, sodium citrate tribasic dihydrate; UPHLC, ultra-high-performance liquid
chromatography.
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injection analysis with fluorescence detector or terbium-sensitized lumines-

cence [120] and DART-Orbitrap-MS [114] have also been applied for the
analysis of mycotoxins using QuEChERS for sample pretreatment.
3.4 Polycyclic Aromatic Hydrocarbon Analysis

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic envi-
ronmental contaminants that contain at least two condensed aromatic rings in
their structures and are produced by incomplete combustion processes. Due to
their demonstrated mutagenic and carcinogenic activity, they have to be
monitored and their sources have to be identified to control their release to the
environment. In this sense, and despite the fact that there are hundreds of these
compounds, the US Environmental Protection Agency (EPA) has established a
list of 16 PAHs as priority pollutants, which includes acenaphthene, ace-
naphthylene, anthracene, benzo[a]anthracene, benzo[a]pyrene, benzo[b]fluo-
ranthene, benzo[g,h,i]perylene, benzo[k]fluoranthene, chrysene, dibenzo[a,h]
anthracene, fluoranthene, fluorine, indeno[1,2,3-cd]pyrene, naphthalene,
phenanthrene and pyrene [121].
Table 4 provides a general overview of the applications of the QuEChERS
method to PAH analysis. As can be seen, most applications in this field have
focused on achieving good recovery values for the 16 PAHs in the priority list
[58,123,126e128,130,132,134], while it is true that many other articles have
included only some of them as target analytes [30,38,59,122,124,125,131,133],
sometimes even substituted variants of those priority PAHs [125,129,131,133].
Besides the 16 regulated PAHs already mentioned, monohydroxylated
PAHs (OH-PAHs) have also been studied by Knobel et al. since they have been
found in milk as detoxification products [129]. Thus their determination is
important because they could be taken as biomarkers to determine cattle
exposure to PAHs and prevent the ingestion of contaminated milk by humans.
It is noteworthy to mention that CE-ultraviolet (UV) was employed for the
determination of these five OH-PAHs, constituting one of the few works in the
literature in which QuEChERS and CE have been combined [129,136,137].
The high number of possible PAH sources has made them one of the most
widespread groups of pollutants in the environment, being found at really high
concentrations in industrialized places [138,139]. This fact, in addition to their
lipophilic nature, results in a higher risk of contamination of foods of animal
origin since they normally have greater fat content. Therefore, it is possible to
find in the literature a wide variety of studied matrices in which the
QuEChERS method has been applied. Among them, animal origin foods
like fish [38,122,133,135], seafood [123,125,126,130,131,134], meat
[124,126,128,132] and milk [129] stand out. However, they have also been
analysed in soils [58], because this matrix is one of the main reservoirs of
PAHs since they tend to be strongly bound to soil organic matter. In this sense,
Cvetkovic et al. [58] have proposed a modification of the original method,
TABLE 4 Some Examples of the Application of the QuEChERS Method to the Analysis of PAHs
Extraction
Analytes (Amount) Solvents Salts d-SPE Step Technique (%) LODs Comments References
16 PAHs Soil (10 g) 30 mL 8 g MgSO4, 2 g 150 mg MgSO4, GCeMS/MS 81e110 0.39e1.53 A mixture [58]
ACN:H2O NaCl 50 mg mg/kg hexane:H2O
2/1 (v/v) diatomaceous was also tested.
earth PSA, C18,
Florisil and
clinoptilolite
were also tried
as cleanup
sorbents.
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Acenaphthene-
d10 and
perylene-d12 as
IS
Benzo[a] Bread (5 g) 10 mL 6 g MgSO4, 1.8 g MgSO4, GCeMS/MS 97e120 0.3 mg/kg 5 mL of [30]
pyrene acetone 1.5 g NaCl 400 mg PSA deionized
water was
added initially.
Anthracene-d10
as IS
13 PAHs Smoked fish (5 g) 10 mL ACN 4 g MgSO4, 1 g 900 mg MgSO4, GCeFID 72e90 1.1e5.5 mg/kg e [38]
NaCl 300 mg PSA,
150 mg C18
5 PAHs Carp fish (2.5 g) 10 mL ACN 2 g MgSO4, 2 g MgSO4, HPLCeFD e e Comparative [122]
0.5 g NaCl 150 mg PSA with Soxhlet
was developed.
Some different
sorbents were
tried
16 PAHs Wild and 10 mL ACN 4 g MgSO4, 1 g 900 mg MgSO4, GCeMS/MS 89e112 0.01e0.99 mg/L 5 deuterated as [123]
commercial NaCl 150 mg PSA ISs
mussels (10 g)
12 PAHs Ham (8 g) 10 mL 4 g MgSO4, 1 g 900 mg MgSO4, GCeMS 72e111 0.1e1 mg/kg Anthracene-d10 [124]
EtOAc NaCl 150 mg PSA, as IS
300 mg C18
14 PAHs Manila clams, 5 mL ACN 2 g MgSO4, 150 mg MgSO4, HPLCeFD 87e116 0.0500e0.5270 Extraction step [125]
hard clams, 0.5 g NaCl 50 mg PSA mg/kg was carried out
oysters, cockles twice
(2 g)
12 PAHs Tea (1 g) 10 mL ACN 4 g MgSO4, 1 g 900 mg MgSO4, GCeMS 50e120 e 10 mL boiling [59]
NaCl 150 mg PSA, water was
150 mg SAX added initially.
One deuterated
IS. LLE step
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after
QuEChERS
16 PAHs Kindling-free- 10 mL ACN 6 g MgSO4, 1200 mg GCeMS 71e104 0.1e2 mg/Lb 10 mL of water [126]
charcoal grilled 1.5 g NaOAc MgSO4, 400 mg was added
poultry meat, red PSA, 400 mg initially.
meat, seafood C18 silica gel Commercial
(5 g) particles QuEChERS kits
16 PAHs Rice grain (10 g) 10 mL ACN 6 g MgSO4, 150 mg MgSO4, GCeMS 70e122 e 10 mL of water [127]
1% acetic 1.5 g NaOAc 50 mg PSA was added
acid (v/v) initially. Six
deuterated ISs
16 PAHs Meat (5 g) 10 mL ACN 6 g MgSO4, 1200 mg GCeMS 71e104 0.1e2 mg/Lb 10 mL of water [128]
1.5 g NaOAc MgSO4, 400 mg was added
PSA, 400 mg initially.
C18 Commercial
QuEChERS kits
5 OH- Milk (1200 mL) 300 mL 480 mg 30 mg PSA, CEeUV 80e105 0.98e3.72 Hydrolysis step [129]
PAHs ACN MgSO4, 30 mg C18 mg/kg prior to
120 mg NaCl QuEChERS
Continued
TABLE 4 Some Examples of the Application of the QuEChERS Method to the Analysis of PAHsdcont’d
Extraction
Analytes (Amount) Solvents Salts d-SPE Step Technique (%) LODs Comments References
16 PAHs Oysters (10 g) 15 mL ACN 6 g MgSO4, 150 mg MgSO4, UHPLCeMS 71e110 13e129 mg/kg 7 mL of water [130]
1.5 g NaCl 50 mg PSA was added
initially.
Commercial
QuEChERS kits
17 PAHs Sea urchin (1 g) 1 mL ACN 600 mg MgSO4, 90 mg MgSO4, GCeMS/MS 70e120a 0.7e1.5 mg/kgb e [131]
150 mg NaOAc 30 mg PSA,
15 mg C18
16 PAHs Chicken and 10 mL ACN 6 g MgSO4, 1200 mg GCeMS 71e104 0.1e2 mg/Lb 10 mL of water [132]
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duck meat (5 g) 1.5 g NaOAc MgSO4, 400 mg was added
PSA, 400 mg initially.
C18 Commercial
QuEChERS kits
33 PAHs Salmon (1 g) 2 mL Method 1: 6 g 150 mg MgSO4, GCeMS 70e120a 2e10 mg/kg 2 deuterated [133]
acetone: MgSO4, 1.5 g 50 mg PSA, ISs. Commercial
EtOAc: NaOAc 50 mg C18 QuEChERS kits.
isooctane Method 2: 4 g Comparison
2/2/1 (v/v/v) MgSO4, 1 g with EN and
NaOAc, 1 g tri- AOAC methods
Na, 0.5 g di-Na
16 PAHs Shrimp (10 g) 10 mL ACN 6 g MgSO4, 150 mg MgSO4, UFLCeMS/ 70e120a 20e510 mg/kg Commercial [134]
1.5 g NaCl 50 mg PSA MS QuEChERS kits
16 PAHs Fish (5 g) 8 mL ACN 6 g MgSO4, 900 mg MgSO4, HPLCeFD 70e120a 0.09e1.40 mg/L Commercial [135]
1.5 g NaOAc 300 mg PSA, QuEChERS kits
150 C18
ACN, acetonitrile; AOAC, Association of Analytical Communities; C18, octadecylsilane; CEeUV, capillary electrophoresiseultraviolet; di-Na, sodium citrate dibasic sesquihydrate; EN,
European norm; EtOAc; ethyl acetate; FD, fluorescence detector; FID, flame ionization detector; GC, gas chromatography; HPLC, high-performance liquid chromatography; IS, internal
standard; LLE, liquideliquid extraction; LOD, limit of detection; MS, mass spectrometry; NaOAc, sodium acetate; OH-PAH, monohydroxylated polycyclic aromatic hydrocarbon; PAH,
polycyclic aromatic hydrocarbons; PSA, N-propylethylendiamine; SAX, strong anion exchanger; tri-Na, sodium citrate tribasic dihydrate; UFLC, ultra-fast-liquid chromatography.
a
Recovery values were found between 70% and 120% for most of analytes determined.
b
Instrumental LOD.
ARTICLE IN PRESS
consisting of the same LLE step but using diatomaceous earth as d-SPE sor-
bent, for the extraction of the 16 PAHs listed by the US EPA from soil samples.
This extraction procedure allowed obtaining high recovery and good cleanup
power. Fig. 5 shows a comparison of the GCeMS chromatograms obtained
when a standard, a blank and a spiked sample were analysed.
Moreover, food contamination can take place due to the production of
PAHs during thermal processing (e.g., smoking, roasting, grilling, drying).
Thus, matrices subjected to drying or roasting processes in which wood
burning is involved have also been studied, including tea [59], rice grain [127]
or bread [30], whose raw materials may have been subjected to these kinds of
processing methods. In this sense, animal origin foods, which are often grilled,
smoked or baked, have also been analysed [38,126].
In relation to the solvents, salts and sorbents used to carry out the
QuEChERS method for the extraction of PAHs, it should be highlighted that
very few changes have been made with respect to the original method. Thus,
almost all articles have used the original solvent (ACN) and salts (MgSO4
and NaCl) in the extraction step [38,58,59,122,123,125,129,130,134]. How-
ever, some articles have proposed some slight modifications such as the use of
buffers like citrate [133] or changes in the type of salt, for example, sodium
acetate (NaOAc) [126e128,131,132,135]. Several authors have also proposed
alternative solvents like acetone or EtOAc, and also mixtures of solvents like
ACN:water or acetone:EtOAc:isooctane, to improve the recovery of the method
[30,124,133]. In this sense, Forsberg et al. [133] proposed the use of a solvent
mixture (acetone, EtOAc and isooctane) in combination with AOAC and CEN
official methods for the extraction of 33 PAHs from fish, resulting in a better
extraction performance than that obtained when official methods are applied.
The authors suggested that the higher miscibility of acetone and EtOAc with
water facilitates PAH transfer to isooctane from water-sealed matrix pores.
Regarding the cleanup step, it seems clear that the sorbent mostly used has
been, once more, PSA [30,38,59,122e135] in the presence of MgSO4 and,
very often, in combination with C18 to diminish the fat content of the final
extract when samples required its use. Only a few articles have proposed the
use of different materials as sorbents to be included in this step. As an
example, Cvetkovic and co-workers [58] have proposed the first use of dia-
tomaceous earth (composed principally of 87%e91% of SiO2, although they
also contain Al2O3 and Fe2O3) as cleanup sorbent, while Sadowska-Rociek
et al. [59] have suggested the use of PSA in combination with an SAX sorbent,
suitable for the extraction of compounds such as carboxylic acids. Finally, it is
noteworthy to mention that it is not possible to use GCB because PAHs are
apolar planar compounds and are highly retained by this sorbent.
Apart from the application of QuEChERS for PAH determination, GC and
LC have also been used, although it is true that the most extended separation
techniques have been GC, generally coupled to an MS detector
[30,58,59,123,124,126e128,131e133]. Although commented at the beginning
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FIGURE 5 GCeMS chromatograms of (A) standard solution at 19.23 mg/mL (B) blank sample
(C) spiked sample (ACN:water:diatomaceous earth); (1) phenol-d6; (2) 2-chlorphenol-3,4,5,6-d4;
(3) 1,2- dihlorbenzen-d4; (4) nitrobenzene-d5; (5) naphthalene; (6) 2-fluorobiphenyl; (7) ace-
naphthylene; (8) acenaphthene-d10; (9) acenaphthene; (10) fluorene; (11) 2,4,6-tribromophenol;
(12) phenanthrene; (13) anthracene; (14) fluoranthene; (15) pyrene; (16) p-terphenyl-d14; (17)
chrysene; (18) benzo[a]anthracene; (19) benzo[b]fluoranthene; (20) benzo[k]fluoranthene; (21)
benzo[a]pyrene; (22) perylene-d12; (23) indeno[1,2,3-cd]pyrene; (24) dibenzo[a,h]anthracene; (25)
benzo[g,h,i] perylene. ACN, acetonitrile; GC, gas chromatography; MS, mass spectrometry.
Reprinted from J.S. Cvetkovic, V.D. Mitic, V.P.S. Jovanovic, M.V. Dimitrijevic, G.M. Petrovic, S.D.
Nikolic-Mandic, G.S. Stojanovic, Optimization of the QuEChERS extraction procedure for the
determination of polycyclic aromatic hydrocarbons in soil by gas chromatography-mass spec-
trometry, Anal. Methods 8 (2016) 1711e1720 with permission of Royal Society of Chemistry.
ARTICLE IN PRESS
of this section, it should be pointed out again the work of Knobel and co-
workers [129] since capillary zone electrophoresis has been applied for the
determination of OH-PAHs, taking advantage of their capacity to be ionized.
Finally, it has to be mentioned that all methodologies based on the
QuEChERS method and developed for the analysis of PAHs have shown
excellent results, with recovery values generally being in the range 70%e
120%, although it should be highlighted that many authors have made use of
ISs during the process. Apart from good recovery data, LODs provided by
these methodologies are in the range of a few mg/kg or mg/L. Hence, judging
by the data shown in Table 4, it seems clear that the QuEChERS method has
shown to have a good performance in PAH analysis.
3.5 Miscellaneous
Apart from the analytes previously mentioned, the QuEChERS method has
also been used to analyse, among others, personal care products [140,141],
flame retardants [140,142], industrial chemicals [140,143], polybrominated
diphenyl ethers [144] and polychlorinated biphenyls [140,145], UV filters
[140], hormones [146,147], marine toxins [148,149], compounds of interest in
the agrifood industry [150] (i.e., possible contaminants [150,151] and natural
substances [152], plant compounds [60,153]), siloxanes [35], lipids [154] and
phthalates [155].
Table 5 shows some examples of such applications. It is worth mentioning
that the robustness of this method has allowed the simultaneous extraction of
different families of compounds [24,140,157] (including those previously
mentioned as well as pesticides, pharmaceuticals, mycotoxins and PAHs) with
optimum results. As an example, Plassmann et al. developed a methodology to
determine 64 compounds from 14 different families [140]. For this purpose, a
non-buffered extraction step using 5 mL of ACN, 2 g of MgSO4 and 0.5 g of
NaCl and a d-SPE with PSA and MgSO4 were used. The efficiency of the
selected method was compared with that obtained using only the LLE step
(similar recovery but higher background in chromatography were achieved) or
using formate- or citrate-buffered QuEChERS (with coloured and turbid ex-
tracts). It is important to note that despite the versatility of the QuEChERS
method, recovery was higher than 70% for 47 compounds in pig and human
blood. The authors explained the losses of the 17 remaining compounds by
means of the evaporation and PSA sorption.
The mentioned analytes have been determined in almost all types of liquid
[140,156,158] and solid samples [24,35,144,146,148,151,153,156] including
biological samples (blood [140,153,156], urine [156], human tissues [156],
plasma [154] and cerebrospinal fluid [159]), industrial products (hygiene
products [141], food contact paper [151]), environmental matrices (sediments
and soils [35,144,146], plants [35,60] and water [158]) and foods (soy prod-
ucts [24], beverages [160], meat [150], fish and seafood [148], milk and
TABLE 5 Some Examples of the Application of the QuEChERS Method to the Analysis of Miscellaneous Compounds
Extraction
64 Multiresidue Blood (5 mL) 5 mL ACN 2 g MgSO4, 375 mg HPLCeMS/ 70 for 47 1e128 A stainless-steel ball [140]
compounds (10 0.5 g NaCl MgSO4, MS, GCeMS compounds mg/L was added to break
cosmetic 62.5 mg PSA clots formed after
ingredients addition of ACN.
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potentially QuEChERS, LLE
allergenic, 5 (similar to first
aromatic amines, QuEChERS step),
10 flame QuEChERS using
retardants, 5 other salt
industrial combination (2 g
chemical MgSO4 þ 0.5 g
additives, 4 NaCl þ 5 g tri-
pesticides, 3 Na þ 0.25 g di-Na or
PAHs, 3 PCBs, 2 g MgSO4 þ 0.5 g
8 PFCs, 1 phenol, NaCl þ 0.5 g
2 plasticisers, 4 NaCOOH þ 340 mg
preservatives, 3 HCOOH) were
QACs, 2 SVHCs, compared. Better
4 UV filters) results (in terms of
efficiency and
cleaner extracts)
were obtained with
the selected
QuEChERS method
257 Multiresidue Soy isoflavones 10 mL ACN 1 g MgSO4, 200 mg UHPLCeMS/ 70e120 for 0.5e5 8 mL of water was [24]
compounds nutraceutical 1% acetic 0.5 g MgSO4, MS 70 of mg/kg added initially. PSA,
(pesticides and products: acid (v/v) NaOAc 100 mg C18 compounds GCB, C18, Z-Sepþ
mycotoxins) capsules, tablets and a mixture of
and powder them were tested as
presentation (2 g) clean-up sorbents.
Florisil cartridges
were also used in
cleanup step. An
alternative LLE was
tested [extraction
with 7.5 mL ACN 1%
formic acid (v/v)].
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Better results were
obtained with LLE
extraction plus
Florisil cartridges
3 Synthetic Urine (0.10 mL), Liquid e 150 mg UHPLCeMS/ 85e109 0.1 mg/L QuEChERS extracts [156]
cannabinoids blood (0.10 mL), samples: MgSO4, 25 mg MS were passed through
brain, heart 1 mL ACN PSA, 25 mg C18 a lipid capturer
muscle, lung, solid samples: cartridge
liver, spleen, 9 mL ACN
kidney, pancreas,
adipose tissue
(1 g)
6 PBDEs Sediment (1 g) 5 mL e 1.5 g MgSO4, GCeMS/MS 86e113 0.03e0.05 Extraction step was [144]
hexane:DCM 300 mg PSA, mg/kg ultrasonically
1/1 (v/v) 50 mg C18 assisted. C18, PSA
(three times) and GCB were tested
as sorbents.
QuEChERS and PLE
were compared. PLE
provided slightly
lower LODs
Continued
TABLE 5 Some Examples of the Application of the QuEChERS Method to the Analysis of Miscellaneous Compoundsdcont’d
Extraction
6 Steroid Sediment (2.5 g) 10 mL ACN: 6 g MgSO4, 900 mg LCeMS/MS 63e123 0.03e 7.5 mL of water was [146]
hormones isopropanol 1.5 g MgSO4, 0.2 mg/kg added initially.
90/10 (v/v) NaOAc 150 mg PSA Acetate buffer and
citrate buffer (1 g
NaO citrate, 4 g
MgSO4, 1 g NaCl,
0.5 g di-Na) were
compared. Acetate
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buffer provided better
results. PSA, C18 and
GCB were tested as
sorbents
12 Synthetic Personal care 3 mL ACN 2.4 g 180 mg GCeMS 50e112 0.01e Extraction step was [141]
musks products: body MgSO4, MgSO4, 60 mg 5.00 mg/kg ultrasonically
and hair wash, 750 mg PSA, 30 mg C18 assisted
toilet soaps, NaOAc
shaving products,
dentifrice,
deodorants/
antiperspirants,
moisturizers and
perfumes
(500 mg)
13 Paralytic Mussel (1 g) 1 mL 0.1% e 10 mg ABS HPLCeMS/ 83e113 3e708 Proteins were [148]
shellfish formic acid Elut-NEXUS MS mg/kg eliminated before d-
poisoning toxins (v/v) (two sorbent SPE by adding MeOH
times) (polymeric and freezing at
sorbent with 20 C
nonpolar
retention
mechanism)
5 Nitrosamines Cooked bacon 10 mL 4g 300 mg GCeMS/MS 70e120 0.1 mg/kg Fats were removed by [150]
(5 g) ACN:H2O 1/1 ammonium MgSO4, adding 2 mL of
(v/v) formiate 100 mg PSA, hexane saturated
100 mg C18, with ACN in d-SPE
100 mg Z-Sep step
2 Perfluorinated Honey (5g) 10 mL ACN 4 g MgSO4, 900 mg UHPLCeMS/ 82e86 0.016e 5 mL of water was [143]
compounds 0.15% formic 1 g NaCl MgSO4, MS 0.040 mg/ added initially. PSA,
acid (v/v) 150 mg styrene- kg SAX, aminopropyl,
divinylbenzene C18 and Florisil were
also tested as
sorbents
6 Polyphenols Human blood 5 mL ACN 4 g MgSO4, 600 mg HPLCeMS/ 1e64 0.12e Samples were [153]
cells (2 mL) 1% acetic 4 g NaCl MgSO4, MS 48.40 mg/ buffered and
acid (v/v) 100 mg PSA La conjugated analytes
were hydrolysed
before extraction.
Eighteen different
methods made by
combination of
protein precipitation,
LLE and SPE were
also tested
2 Betalains Red beetroot (2 g) 10 mL 4 g MgSO4, 900 mg HPLCeMS e 1.063e PSA, C18, [60]
MeOH:H2O 1 g NaCl, MgSO4, 1.166 mg/ aminoporpyl, Florisil,
90/10 (v/v) 0.01 g di- 150 mg SAX kg silica gel and styrene-
Na, 1 g tri- divinylbenzene were
Na also used as sorbents
9 Siloxanes Pine needles, 10 mL 6 g MgSO4, 900 mg GCeMS 56e63 1.845e e [35]

soils (2.5 g) DCM:hexane 1.5 g MgSO4, 19.853 ng/
1/1 (v/v) NaOAc 300 mg PSA kg
150 mg C18
ACN, acetonitrile; C18, octadecylsilane; DCM, dichloromethane; di-Na, sodium citrate dibasic sesquihydrate; d-SPE, dispersive solid-phase extraction; GC, gas chromatography; GCB, graphitized
carbon black; HPLC, high-performance liquid chromatography; LLE, liquideliquid extraction; LOD, limit of detection; MeOH, methanol; MS, mass spectrometry; NaOAc, sodium acetate;
PAH, polycyclic aromatic hydrocarbons; PBDE, polybrominated diphenyl ether; PCB, polychlorinated biphenyl; PFC, perflourinated compound; PLE, pressurized liquid extraction;
PSA, N-propylethylendiamine; QAC, quaternary ammonium compound; SAX, strong anion exchanger; SVHC, substance of very high concern; tri-Na, sodium citrate tribasic dihydrate;
UHPLC, ultra-high-performance liquid chromatography; UV, ultraviolet.
a
Limit of quantification.
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derivatives [161,162], honey and beehive products [143] and fruits, vegetables
and derivatives [155,157]).
The vast majority of the mentioned articles have used ACN as solvent of
extraction with variable proportions of NaCl and MgSO4. However, certain
applications required specific and distinctive solvents (such as MeOH [60]) or
mixtures of them (e.g., hexane:DCM 1/1 (v/v) [35,144], ACN:isopropanol 90/
10 (v/v) [146], CHCl3:MeOH 2/1 (v/v) [154]). This step is frequently carried
out in buffered media. Thus, the pH value was controlled in such applications
by the addition of an acetate [24,141,146] or citrate buffer [60] and formic
[143,148] or acetic acid [24,153].
Regarding the d-SPE step, the preferred sorbent was, without any doubt,
PSA followed by C18. However, other sorbents have been used or tested in the
cleanup step, including the ‘classical’ sorbents such as GCB [24,144,146],
silica gel [60], aminopropyl [60,143], an SAX [60] and Florisil [60,143] or
alternative materials such as Z-Sep/Z-Sepþ [24], styrene-divinylbenzene
[143] and polymeric sorbents [148]. The selection of the sorbent or the
combination of them was usually made by comparing the results (in terms of
efficiency, recovery and/or cleaning) obtained with each particular material or
mixture.
Generally, QuEChERS provide clean extracts with high recovery. How-
ever, in certain cases, and depending on the nature of the analysed samples and
compounds, an additional step to remove proteins or fats was performed
[148,150,156], both before and after the d-SPE step. Similarly, and not only to
remove proteins/fats but also other interferences of the matrix, some authors
added an additional extraction step (usually DLLME or SPE). In this regard,
Faraji et al. [163] applied a DLLME with the ionic liquid 1-hexyl-3-
methylimidazolium hexafluorophosphate ([HMIm][PF6]) as extractant after
the QuEChERS methodology (10 g of sample extracted with 10 mL ACN, 4 g
anhydrous MgSO4 and 1 g NaCl and cleaned with 50 mg of PSA and 300 mg
MgSO4; 25 mg of C18 was also used for sauce samples). The application of
50 mL [HMIm][PF6] (with water as dispersive solvent) allowed the detection
of bisphenol A in canned foods (lentil, pinto beans in tomato sauce and canned
spaghetti sauce) at 0.1 mg/L with recovery higher than 90%.
The separation techniques and determination methods most commonly
applied in these cases were LC (both HPLC [60,140,146,148,153,156] or
UHPLC [24,143] modes) and GC [35,140,141,144,150] mostly coupled to MS
[35,60,140,141] or MS/MS [24,140,143,144,146,148,150,153,156]. However,
CE has also been used, once more, to a lesser extent [136,137].
It is worth noting that some authors [137,140,154,157,164] compared the
efficiency of the optimized QuEChERS method with other well-established
extraction techniques [i.e., LLE, the Folch method (used in the extraction of
lipids), pseudomodified QuEChERS (avoiding the d-SPE step), microwave-
assisted solvent extraction, classical SPE, and PLE (coupled to gel permeation
chromatography or SPE)]. Commonly, QuEChERS provided better or
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comparable results in terms of efficiency, speed, solvent and reagent con-

sumption and economic cost. However, some examples could be found
[137,157] in which QuEChERS was not the preferred method since better
results were obtained with alternative procedures. In this respect, Fan et al.
[157] compared three different methods to extract 201 multiclass pesticides
and chemical pollutants in tea: (1) a double acidic ACN extraction followed by
cleanup with classical SPE cartridges (made of three types of materials, which
employ different mechanisms and entail interactions with colourants, organic
acids, bases and polyphenols as well as nonpolar interfering substance); (2) an
acetate-buffered QuEChERS method with GCB and PSA as d-SPE sorbents;
and (3) a double extraction with ACN with NaCl, removal of water with
MgSO4 and cleanup by the previously selected classical SPE cartridge. The
third method demonstrated not to be useful because less than 4% of analytes
were extracted with high recovery. The other two methods showed similar
efficiencies in terms of recovery, but the classical method showed superior
effectivity in removing pigments.
4. CONCLUSIONS AND FUTURE TRENDS

Current trends in analytical chemistry, under the principles of GAC, are ori-
ented to the development of high-throughput multiresidue methods. In this
regard, methods should be easy to handle, rapid, and with low cost and
minimum requirements of sample, solvent volumes and reagents. Moreover, it
is highly desirable that they provide a high selectivity for a broad range of
analytes without applying complicated cleanup approaches.
Under such standpoint, the introduction of the QuEChERS method came
up as an alternative streamlined sample preparation approach to determine
pesticide residues in fruits and vegetables. However, its inherent advantages
favoured an exponential growth beyond its original scope of application. In
fact, QuEChERS has quickly evolved through experimentation and validation
to use different solvents, buffering salts (to increase recovery of pH-dependent
analytes) and sorbents that allow increasing the number and types of extracted
analytes as well as the complexity of studied matrices.
Nowadays, the technique is particularly useful to extract polar and basic
compounds from various matrices, particularly fruits, vegetables and other
food products. Furthermore, apart from pesticides from agricultural products,
QuEChERS has proved to be effective in the extraction of different organic
contaminants, such as mycotoxins, volatile organic compounds, PAHs and
pharmaceutical compounds, from foods and drinks, biological samples and
environmental matrices. However, and despite these positive results, certain
applications have yet to be fully investigated.
Although most applications of QuEChERS have been oriented to
contaminant analysis, there are some examples of its use for the determina-
tion of naturally occurring compounds. Due to the potential benefits of such
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substances and to the demonstrated efficiency of QuEChERS, it would not be

surprising that this method could be greatly applied in this field in the future.
Another important future perspective on QuEChERS, as in the great
majority of analytical methodologies that are being developed, could be
orientated towards its automation due to the increasing number of samples
entering every day in any analytical laboratory. QuEChERS is basically a
manual procedure with different steps. Until now, automation has been mainly
oriented to the commercial availability of preweighed salts, buffers and sor-
bents with the aim to reduce the time devoted to this step. In fact, there are
many different combinations marketed (almost any desired recipe is available)
by some companies. However, the attempts to automate other steps or the
complete procedure are more limited. In particular, different approaches have
been developed using disposable pipette extraction [165,166] (d-SPE tech-
nique that can be fully automated and applied instead of typically used
involving centrifugation), mini-SPE cartridges [167] with an autosampler to
automate the different steps, online SPE cartridges [168] or fully automated
devices [169e172] that carry out liquid dispensing/pipetting, vortex mixing,
vial shaking, opening/closing sample vials, addition of solid reagents, identi-
fying liquid levels, decanting, centrifugation, matrix spiking and d-SPE
cleanup. In the next few years, new approaches on this topic will be developed,
and these kinds of devices will be probably established as routine techniques in
different laboratories (due to their intrinsic advantages particularly for labo-
ratories with limited staff).
ACKNOWLEDGEMENTS
B.S.R. and J.G.S would like to thank the Canary Agency of Economy, Industry, Trade and
Knowledge of the Government of the Canary Islands for the FPI fellowship (cofinanced with
an 85% from European Social Funds).
REFERENCES
[1] US Environmental Protection Agency, Basics of Green Chemistry. https://www.epa.gov/
greenchemistry/basics-green-chemistry.
[1a] S. Armenta, F.A. Esteve-Turrillas, S. Garrigues, M. de la Guardia, Green analytical
chemistry: the role of green extraction techniques, in: E. Ibanez, A. Cifuentes (Eds.),
Green Extraction Techniques: Principles, Advances and Applications, vol. 76, 2017,
(in this volume).
[2] R.L. Pérez, G.M. Escandar, Experimental and chemometric strategies for the development
of green analytical chemistry (GAC) spectroscopic methods for the determination of
organic pollutants in natural waters, Sustain. Chem. Pharm. 4 (2016) 1e12.
[3] A.B. Eldin, O.A. Ismaiel, W.E. Hassan, A.A. Shalaby, Green analytical chemistry:
opportunities for pharmaceutical quality control, J. Anal. Chem. 71 (2016) 861e871.
[4] M. Koel, Do we need green analytical chemistry? Green Chem. 18 (2016) 923e931.
ARTICLE IN PRESS
[5] A. Gałuszka, P. Konieczka, Z.M. Migaszewski, J. Namiesnik, Analytical eco-scale for

assessing the greenness of analytical procedures, TrAC-Trend. Anal. Chem. 37 (2012)
61e72.
[6] S. Armenta, S. Garrigues, M. de la Guardia, The role of green extraction techniques in
green analytical chemistry, TrAC-Trend. Anal. Chem. 71 (2015) 2e8.
[7]
M. Anastassiades, S.J. Lehotay, D. Stajnbaher, F.J. Schenck, Fast and easy multiresidue
method employing acetonitrile extraction/partitioning and “dispersive solid-phase extrac-
tion” for the determination of pesticide residues in produce, J. AOAC Int. 86 (2003)
412e431.
[8] M.L. Schmidt, N.H. Snow, Making the case for QuEChERS-gas chromatography of drugs,
TrAC-Trend. Anal. Chem. 75 (2016) 49e56.
[9] M.Á. González-Curbelo, B. Socas-Rodrı́guez, A.V. Herrera-Herrera, J. González-Sálamo,
J. Hernández-Borges, M.Á. Rodrı́guez-Delgado, Evolution and applications of the
QuEChERS method, TrAC-Trend. Anal. Chem. 71 (2015) 169e185.
[10] T. Rejczak, T. Tuzimski, A review of recent developments and trends in the QuEChERS
sample preparation approach, Open Chem. 13 (2015) 980e1010.
[11] M.C. Bruzzoniti, L. Checchini, R.M. De Carlo, S. Orlandini, L.R.M. Del Bubba,
QuEChERS sample preparation for the determination of pesticides and other organic
residues in environmental matrices: a critical review, Anal. Bioanal. Chem. 406 (2014)
4089e4116.
[12] S.J. Lehotay, QuEChERS sample preparation approach for mass spectrometric analysis of
pesticide residues in foods, Methods Mol. Biol. 747 (2011) 65e91.
[13] G. Martı́nez-Domı́nguez, P. Plaza-Bolaños, R. Romero-González, A. Garrido-Frenich,
Analytical approaches for the determination of pesticide residues in nutraceutical products
and related matrices by chromatographic techniques coupled to mass spectrometry, Talanta
118 (2014) 277e291.
[14] European Committee for Standardization (CEN) Standard Method EN 15662, Food of plant
origin - determination of pesticide residues using GC-MS and/or LC-MS/MS following
acetonitrile extraction/partitioning and clean-up by dispersive SPE e QuEChERS method.
[15] AOAC Official Method 2007.01, Pesticide residues in foods by acetonitrile extraction and
partitioning with magnesium sulfate, AOAC Int., Gaithersburg, USA, 2007.
[16] P.A. Mills, J.H. Onley, R.A. Guither, Rapid method for chlorinated pesticide residues in
non fatty food, J. Assoc. Off. Anal. Chem. 46 (1963) 186e191.
[17] M. Luke, J.E. Froberg, H.T. Masumoto, Extraction and cleanup of organochlorine,
organophosphate, organonitrogen, and hydrocarbon pesticides in produce for
determination by gas-liquid chromatography, J. Assoc. Off. Anal. Chem. 58 (1975)
1020e1026.
[18] W. Specht, S. Pelz, W. Gilsbach, Gas-chromatographic determination of pesticide residues
after clean-up by gel-permeation chromatography and mini-silica gel-column chroma-
tography, Fresenius J. Anal. Chem. 353 (1995) 183e190.
[19] S.J. Lehotay, A.R. Lightfield, J.A. Harman-Fetcho, D.A. Donoghue, Analysis of pesticide
residues in eggs by direct sample introduction/gas chromatography/tandem mass spec-
trometry, J. Agric. Food Chem. 49 (2001) 4589e4596.
[20] M. Anastassiades, E. Scherbaum, B. Tasdelen, D. Stajnbaher, Recent developments in
QuEChERS methodology for pesticide multiresidue analysis, in: H. Ohkawa,
H. Miyagawa, P.W. Lee (Eds.), Pesticide Chemistry. Crop Protection, Public Health,
Environmental Safety, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007.
ARTICLE IN PRESS
[21] K. Mastovska, K.J. Dorweiler, S.J. Lehotay, J.S. Wegscheid, K.A. Szpylka, Pesticide
multiresidue analysis in cereal grains using modified QuEChERS method combined with
automated direct sample introduction GC-TOF-MS and UPLC-MS/MS techniques, J.
Agric. Food Chem. 58 (2010) 5959e5972.
[22] Y. Xing, W. Meng, W. Sun, D. Li, Z. Yu, L. Tong, Y. Zhao, Simultaneous qualitative and
quantitative analysis of 21 mycotoxinsin Radix Paeoniae Alba by ultra-high performance
liquid chromatography quadrupole linear ion trap mass spectrometry and QuEChERS for
sample preparation, J. Chromatogr. B 1031 (2016) 202e213.
[23] L. Norambuena-Subiabre, M.P. González, S. Contreras-Lynch, Uptake and depletion curve
of diflubenzuron in marine mussels (Mytilus chilensis) under controlled conditions,
Aquaculture 460 (2016) 69e74.
[24] G. Martı́nez-Domı́nguez, R. Romero-González, F.J. Arrebola, A. Garrido-Frenich, Multi-
class determination of pesticides and mycotoxins in isoflavones supplements obtained from
soy by liquid chromatography coupled to orbitrap high resolution mass spectrometry, Food
Control 59 (2016) 218e224.
[25] M.Á. González-Curbelo, S.J. Lehotay, J. Hernández-Borges, M.Á. Rodrı́guez-Delgado,
Use of ammonium formate in QuEChERS for high-throughput analysis of pesticides in
food by fast, low-pressure gas chromatography and liquid chromatography tandem mass
spectrometry, J. Chromatogr. A 1358 (2014) 75e84.
[26] L. Han, Y. Sapozhnikova, S.J. Lehotay, Streamlined sample clean-up using combined
dispersive solid-phase extraction and in-vial filtration for analysis of pesticides and envi-
ronmental pollutants in shrimp, Anal. Chim. Acta 827 (2014) 40e46.
[27] M. Anastassiades, Crl-srm 1st Joint CRL Workshop, 2006. Stuttgart, http://www.eurl-
pesticides.eu/library/docs/srm/1stws2006_lecture_anastassiades_quechers.pdf.
[28] H. Chen, J. Marı́n-Sáez, R. Romero-González, A. Garrido Frenich, Simultaneous deter-
mination of atropine and scopolamine in buckwheat and related products using modified
QuEChERS and liquid chromatography tandem mass spectrometry, Food Chem. 218
(2017) 173e180.
[29] Y. Yu, X. Liu, Z. He, L. Wang, M. Luo, Y. Peng, Q. Zhou, Development of a multi-residue
method for 58 pesticides in soil using QuEChERS and gas chromatography-tandem mass
spectrometry, Anal. Methods 8 (2016) 2463e2470.
[30] S. Eslamizad, F. Kobarfard, K. Javidnia, R. Sadeghi, M. Bayat, S. Shahanipour,
N. Khalighian, H. Yazdanpanah, Determination of benzo[a]pyrene in traditional,
industrial and semiindustrial breads using a modified QuEChERS extraction, dispersive
SPE and GC-MS and estimation of its dietary intake, Iran, J. Pharm. Res. 15 (2016)
165e174.
[31] X.-Q. Liua, Y.-F. Li, W.-T. Meng, D.-X. Li, H. Sun, L. Tong, G.-X. Suna, A multi-residue
method for simultaneous determination of 74 pesticides in Chinese material medica using
modified QuEChERS ample preparation procedure and gas chromatography tandem mass
spectrometry, J. Chromatogr. B 1015e1016 (2016) 1e12.
[32] C. Guo, M. Wang, H. Xiao, B. Huai, F. Wang, G. Pan, X. Liao, Y. Liu, Development of a
modified QuEChERS method for the determinationof veterinary antibiotics in swine
manure by liquid chromatography tandem mass spectrometry, J. Chromatogr. B 1027
(2016) 110e118.
[33] Y.-H. Chuang, Y. Zhang, W. Zhang, S.A. Boyd, H. Li, Comparison of accelerated
solvent extraction and quick, easy, cheap, effective, rugged and safe method for
extraction and determination of pharmaceuticals in vegetables, J. Chromatogr. A 1404
(2015) 1e9.
ARTICLE IN PRESS
[34] X. Xu, X. Zhang, E. Duhoranimana, Y. Zhang, P. Shu, Determination of methenamine

residues in edible animal tissues by HPLC-MS/MS using a modified QuEChERS method:
validation and pilot survey in actual samples, Food Control 61 (2016) 99e104.
[35] S. Ramos, J.A. Silva, V. Homem, A. Cincinelli, L. Santos, A. Alves, N. Ratola, Solvent-
saving approaches for the extraction of siloxanes from pine needles, soils and passive air
samplers, Anal. Methods 8 (2016) 5378e5387.
[36] S.S. Herrmann, M.E. Poulsen, Clean-up of cereal extracts for gas chromatography-tandem
quadrupole mass spectrometry pesticide residues analysis using primary secondary amine
and C18, J. Chromatogr. A 1423 (2015) 47e53.
[37] F. Saladino, L. Manyes, F.B. Luciano, J. Mañes, M. Fernandez-Franzon, G. Meca,
Bioactive compounds from mustard flours for the control of patulin production in wheat
tortillas, LWT e Food Sci. Tech. 66 (2016) 101e107.
[38] M.T. Ahmed, F. Malhat, N. Loutfy, Residue levels, profiles, emission source and daily
intake of polycyclic aromatic hydrocarbons based on smoked fish consumption, an
Egyptian pilot study, Polycycl. Aromat. Comp. 36 (2016) 183e196.
[39] P.J. Fernandes, N. Barros, J.L. Santo, J.S. Câmara, High-throughput analytical strategy
based on modified QuEChERS extraction and dispersive solid-phase extraction clean-up
followed by liquid chromatography-triple- quadrupole tandem mass spectrometry for
quantification of multiclass mycotoxins in cereals, Food Anal. Method 8 (2015)
841e856.
[40] A. Rúbies, L. Guo, F. Centrich, M. Granados, Analysis of non-steroidal anti-inflammatory
drugs in milk using QuEChERS and liquid chromatography coupled to mass spectrometry:
triple quadrupole versus Q-orbitrap mass analyzers, Anal. Bioanal. Chem. 408 (2016)
5769e5778.
[41] N. Pang, T. Wang, J. Hu, Method validation and dissipation kinetics of four herbicides in
maize and soil using QuEChERS sample preparation and liquid chromatography tandem
mass spectrometry, Food Chem. 190 (2016) 793e800.
[42] H. Boudra, B. Rouillé, B. Lyan, D.P. Morgavi, Presence of mycotoxins in sugar beet pulp
silage collected in France, Anim. Feed Sci. Tech. 205 (2015) 131e135.
[43] L. Li, W. Li, D.M. Qin, S.R. Jiang, F.M. Liu, Application of graphitized carbon black to the
QuEChERS method for pesticide multiresidue analysis in spinach, J. AOAC Int. 92 (2009)
538e547.
[44] S.J. Lehotay, M. Anastassiades, R.E. Majors, The QuEChERS revolution, LCGC Europe
23 (2010) 418e429.
[45] J.F. Huertas-Pérez, N. Arroyo-Manzanares, L. Havlı́ková, L. Gámiz-Gracia, P. Solich,
A.M. Garcı́a-Campaña, Method optimization and validation for the determination of eight
sulfonamides in chicken muscle and eggs by modified QuEChERS and liquid chroma-
tography with fluorescence detection, J. Pharmaceut. Biomed. 124 (2016) 261e266.
[46] H.-Y. Liu, S.-L. Lin, M.-R. Fuh, Determination of chloramphenicol, thiamphenicol and
florfenicol in milk and honey using modified QuEChERS extraction coupled with poly-
meric monolith-based capillary liquid chromatography tandem mass spectrometry, Talanta
150 (2016) 233e239.
[47] T. Tuzimski, T. Rejczak, Application of HPLC-DAD after SPE/QuEChERS with ZrO2-
based sorbent in d-SPE clean-up step for pesticide analysis in edible oils, Food Chem. 190
(2016) 71e79.
[48] T. Rejczak, T. Tuzimski, QuEChERS-based extraction with dispersive solid phase
extraction clean-up using PSA and ZrO2-based sorbents for determination of pesticides in
bovine milk samples by HPLC-DAD, Food Chem. 217 (2017) 225e233.
ARTICLE IN PRESS
[49] S. Walorczyk, D. Dro_zd_zynski, R. Kierzek, Two-step dispersive-solid phase

extraction strategy for pesticide multiresidue analysis in a chlorophyll-containing matrix
by gas chromatography-tandem mass spectrometry, J. Chromatogr. A 1412 (2015)
22e32.
[50] P. Kaczy nski, B. Łozowicka, M. Jankowska, I. Hrynko, Rapid determination of acid her-
bicides in soil by liquid chromatography with tandem mass spectrometric detection based
on dispersive solid phase extraction, Talanta 152 (2016) 127e136.
[51] J.S. Munaretto, L. Yonkos, D.S. Aga, Transformation of ionophore antimicrobials in
poultry litter during pilot-scale composting, Environ. Pollut. 212 (2016) 392e400.
[52] P.A. Souza Tette, F.A. da Silva Oliveira, E.N. Corrêa Pereira, G. Silva, M.B. de Abreu
Glória, C. Fernandes, Multiclass method for pesticides quantification in honey by means of
modified QuEChERS and UHPLC-MS/MS, Food Chem. 211 (2016) 130e139.
[53] F. Volpatto, A.D. Wastowski, G. Bernardi, O.D. Prestes, R. Zanella, M.B. Adaime, Eval-
uation of QuEChERS sample preparation and gas chromatography coupled to mass
spectrometry for the determination of pesticide residues in grapes, J. Braz. Chem. Soc. 27
(2016) 1533e1540.
[54] Y. Han, L. Song, N. Zou, R. Chen, Y. Qin, C. Pan, Multi-residue determination of 171
pesticides in cowpea using modified QuEChERS method with multi-walled carbon
nanotubes as reversed-dispersive solid-phase extraction materials, J. Chromatogr. B 1031
(2016) 99e108.
[55] Y. Chen, S. Cao, L. Zhang, C. Xi, Z. Chen, Modified QuEChERS combination with
magnetic solid-phase extraction for the determination of 16 preservatives by gas chro-
matography-mass spectrometry, Food Anal. Method. (2016). http://dx.doi.org/10.1007/
s12161-016-0616-1.
[56] Y.-F. Li, L.-Q. Qiao, F.-W. Li, Y. Ding, Z.-J. Yang, M.-L. Wang, Determination of multiple
pesticides in fruits and vegetables using a modified quick, easy, cheap, effective, rugged
and safe method with magnetic nanoparticles and gas chromatography tandem mass
spectrometry, J. Chromatogr. A 1361 (2014) 77e87.
[57] H.-B. Zheng, Q. Zhao, J.-Z. Mo, Y.-Q. Huang, Y.-B. Luo, Q.-W. Yu, Y.-Q. Feng, Quick,
easy, cheap, effective, rugged and safe method with magnetic graphitized carbon black and
primary secondary amine as adsorbent and its application in pesticide residue analysis, J.
Chromatogr. A 1300 (2013) 127e133.
[58] J.S. Cvetkovic, V.D. Mitic, V.P.S. Jovanovic, M.V. Dimitrijevic, G.M. Petrovic,
S.D. Nikolic-Mandic, G.S. Stojanovic, Optimization of the QuEChERS extraction pro-
cedure for the determination of polycyclic aromatic hydrocarbons in soil by gas chro-
matography-mass spectrometry, Anal. Methods 8 (2016) 1711e1720.
[59] A. Sadowska-Rociek, M. Surma, E. Cieslik, Comparison of different modifications on
QuEChERS sample preparation method for PAHs determination in black, green, red and
white tea, Environ. Sci. Pollut. Res. 21 (2014) 1326e1338.
[60] T. Sawicki, M. Surma, H. Zielinski, W. Wiczckowki, Development of a new analytical
method for the determination of red beetroot betalains using dispersive solid-phase
extraction, J. Sep. Sci. 39 (2016) 2986e2994.
[61] B.D. Morris, R.B. Schriner, Development of an automated column solid-phase extraction
cleanup of QuEChERS extracts, using a zirconia-based sorbent, for pesticide residue an-
alyses by LC-MS/MS, J. Agric. Food Chem. 63 (2015) 5107e5119.
[62] F.J. Schenk, A.N. Brown, L.V. Podhorniak, A rapid multiresidue method for determination
of pesticides in fruits and vegetables by using acetonitrile extraction/partitioning and solid-
phase extraction column cleanup, J. AOAC Int. 91 (2008) 422e438.
ARTICLE IN PRESS
[63] R.E. Hunter Jr., A.M. Riederer, P.B. Ryan, Method for the determination of organophos-
phorus and pyrethroid pesticides in food via gas chromatography with electron-capture
detection, J. Agric. Food Chem. 58 (2010) 1396e1402.
[64] A. Lozano, Ł. Rajski, N. Belmonte-Valles, A. Uclés, S. Uclés, M. Mezcua,
A.R. Fernández-Alba, Pesticide analysis in teas and chamomile by liquid chromatography
and gas chromatography tandem mass spectrometry using a modified QuEChERS method:
validation and pilot survey in real samples, J. Chromatogr. A 1268 (2012) 109e122.
[65] T.D. Nguyen, B.S. Lee, B.R. Lee, D.M. Lee, G. Lee, A multiresidue method for the
determination of 109 pesticides in rice using the quick easy cheap effective rugged and safe
(QuEChERS) sample preparation method and gas chromatography/mass spectrometry with
temperature control and vacuum concentration, Rapid Commun. Mass Spectrom. 21
(2007) 3115e3122.
[66] L. Geis-Asteggiante, S.J. Lehotay, H. Heinze, Effects of temperature and purity of mag-
nesium sulfate during extraction of pesticide residues using the QuEChERS method, J.
AOAC Int. 95 (2015) 1311e1318.
[67] C.K. Myresiotis, S. Testempasis, Z. Vryzas, G.S. Karaoglanidis, E. Papadopoulou-Mour-
kidou, Determination of mycotoxins in pomegranate fruits and juices using a QuEChERS-
based method, Food Chem. 182 (2015) 81e88.
[68] P. Parrilla-Vázquez, A. Lozano, S. Uclés, M.M. Gómez-Ramos, A.R. Fernández-Alba, A
sensitive and efficient method for routine pesticide multiresidue analysis in bee pollen
samples using gas and liquid chromatography coupled to tandem mass spectrometry, J.
Chromatogr. A 1426 (2015) 161e173.
[69] S. Niell, V. Cesio, J. Hepperle, D. Doerk, L. Kirsch, D. Kolberg, E. Scherbaum,
M. Anastassiades, H. Heinzen, QuEChERS-based method for the multiresidue analysis of
pesticides in beeswax by LC-MS/MS and GCxGC-TOF, J. Agric. Food Chem. 62 (2014)
3675e3683.
[70] U. Koesukwiwat, S.J. Lehotay, K. Mastovska, X.K.J. Dorweiler, N. Leepipatpiboon,
Pesticide multiresidue analysis in cereal grains using modified QuEChERS method com-
bined with automated direct sample introduction GC-TOF-MS and UHPLC-MS/MS
techniques, J. Agric. Food Chem. 58 (2010) 5950e5972.
[71] EURL DataPool. EU Reference Laboratories for Residues of Pesticides. http://www.eurl-
pesticides-datapool.eu.
[72] A. Wilkowska, M. Biziuk, Determination of pesticide residues in food matrices using the
QuEChERS methodology, Food Chem. 125 (2011) 803e812.
[73] Y. Zhang, D. Hu, S. Zeng, P. Lu, K. Zhang, L. Chen, B. Song, Multiresidue determination
of pyrethroid pesticide residues in pepper through a modified QuEChERS method and gas
chromatography with electron capture detection, Biomed. Chromatogr. 30 (2016)
142e148.
[74] Y. Nuapia, L. Chimuka, E. Cukrowska, Assessment of organochlorine pesticide residues in
raw food samples from open markets in two African cities, Chemosphere 164 (2016)
480e487.
[75] J. Alves Ferreira, J.M. Santos Ferreira, V. Talamini, J. de Fátima Facco, T. Medianeira
Rizzetti, O.D. Prestes, M.B. Adaime, R. Zanella, C.B.G. Bottoli, Determination of pesti-
cides in coconut (Cocos nucifera Linn.) water and pulp using modified QuEChERS and
LC-MS/MS, Food Chem. 213 (2016) 616e624.
[76] J. Du, Z. Gridneva, M.C.L. Gay, R.D. Trengove, P.E. Hartmann, D.T. Geddes, Pesticides in
human milk of Western Australian women and their influence on infant growth outcomes:
a cross-sectional study, Chemosphere 167 (2017) 247e254.
ARTICLE IN PRESS
[77] G. Ramadan, M. Al Jabir, N. Alabdulmalik, A. Mohammed, Validation of a method for the

determination of 120 pesticide residues in apples and cucumbers by LC-MS/MS, drug test,
Analysis 8 (2016) 498e510.
[78] T.M. Rizzetti, M. Kemmerich, M.L. Martins, O.D. Prestes, M.B. Adaime, R. Zanella,
Optimization of a QuEChERS based method by means of central composite design for
pesticide multiresidue determination in orange juice by UHPLC-MS/MS, Food Chem. 196
(2016) 25e33.
[79] M.H. Petrarca, J.O. Fernandes, H.T. Godoy, S.C. Cunha, Multiclass pesticide analysis in
fruit-based baby food: a comparative study of sample preparation techniques previous to
gas chromatography-mass spectrometry, Food Chem. 212 (2016) 528e536.
[80] E.A. Nantia, D. Moreno-González, F.P.T. Manfo, L. Gámiz-Gracia, A.M. Garcı́a-Campaña,
QuEChERS-based method for the determination of carbamate residues in aromatic herbs
by UHPLC-MS/MS, Food Chem. 216 (2017) 334e341.
[81] B. Lozowicka, E. Rutkowska, I. Hrynko, Simultaneous determination of 223 pesticides in
tobacco by GC with simultaneous electron capture and nitrogen-phosphorous detection and
mass spectrometric confirmation, Open Chem. 13 (2015) 1137e1149.
[82] M.L. Martinsa, T.M. Rizzetti, M. Kemmerich, N. Saibt, O.D. Prestes, M.B. Adaime,
R. Zanella, Dilution standard addition calibration: a practical calibration strategy for
multiresidue organic compounds determination, J. Chromatogr. A 1460 (2016) 84e91.
[83] B. Lozowicka, G. lyasova, P. Kaczynski, M. Jankowska, E. Rutkowska, I. Hrynko,
P. Mojsak, J. Szabunko, Multi-residue methods for the determination of over four hundred
pesticides in solid and liquid high sucrose content matrices by tandem mass spectrometry
coupled with gas and liquid chromatograph, Talanta 151 (2016) 51e61.
[84] X.-C. Wang, B. Shu, S. Li, Z.-G. Yang, B. Qiu, QuEChERS followed by dispersive liquid-
liquid microextraction based on solidification of floating organic droplet method for
organochlorine pesticides analysis in fish, Talanta 162 (2017) 90e97.
[85] Document SANTE/11945/2015. https://ec.europa.eu/food/sites/food/files/plant/docs/
pesticides_mrl_guidelines_wrkdoc_11945.pdf, 2016.
[86] X. Hou, S.R. Lei, S.T. Qiu, L.A. Guo, S.G. Yi, W. Liu, A multi-residue method for the
determination of pesticides in tea using multi-walled carbon nanotubes as a dispersive solid
phase extraction absorbent, Food Chem. 153 (2014) 121e129.
[87] M.Á. González-Curbelo, M. Asensio-Ramos, A.V. Herrera-Herrera, J. Hernández-Borges,
Pesticide residue analysis in cereal-based baby foods using multi-walled carbon nanotubes
dispersive solid-phase extraction, Anal. Bioanal. Chem. 404 (2012) 183e196.
[88] B. Bresina, M. Piol, D. Fabbro, M.A. Mancini, B. Casetta, C. Del Bianco, Analysis of
organo-chlorine pesticides residue in raw coffee with a modified “quick easy cheap
effective rugged and safe” extraction/clean up procedure for reducing the impact of
caffeine on the gas chromatography-mass spectrometry measurement, J. Chromatogr. A
1376 (2015) 167e171.
[89] Y. Zhang, X. Zhang, B. Jiao, Determination of ten pyrethroids in various fruit juices:
comparison of dispersive liquid-liquid microextraction sample preparation and QuEChERS
method combined with dispersive liquid-liquid microextraction, Food Chem. 159 (2014)
367e373.
[90] D.S. Bol’shakova, V.G. Amelina, A.V. Tret’yakova, Determination of polar pesticides in
soil by micellar electrokinetic chromatography using QuEChERS sample preparation,
Anal. Chem. 69 (2014) 89e97.
[91] J. Wei, J. Cao, K. Tian, Y. Hu, H. Su, J. Wan, P. Li, Trace determination of five
organophosphorus pesticides by using QuEChERS coupled with dispersive liquid-liquid
ARTICLE IN PRESS
microextraction and stacking before micellar electrokinetic chromatography, Anal.

Methods 7 (2015) 5801e5807.
[92] Y. Sapozhnikova, Evaluation of low-pressure gas chromatographytandem mass spec-
trometry method for the analysis of 140 pesticides in fish, J. Agric. Food Chem. 62 (2014)
3684e3689.
[93] S.W.C. Chung, B.T.P. Chan, Validation and use of a fast sample preparation method and
liquid chromatography-tandem mass spectrometry in analysis of ultra-trace levels of 98
organophosphorus pesticide and carbamate residues in a total diet study involving diver-
sified food types, J. Chromatogr. A 1217 (2010) 4815e4824.
[94] V.C. Fernandes, V.F. Domingues, N. Mateus, C. Delerue-Matos, Multiresidue pesticides
analysis in soils using modified QuEChERS with disposable pipette extraction and
dispersive solid-phase extraction, J. Sep. Sci. 36 (2013) 376e382.
[95] I.-S. Jeong, B.-M. Kwak, J.-H. Ahn, S.-H. Jeong, Determination of pesticide residues in
milk using a QuEChERS-based method developed by response surface methodology, Food
Chem. 133 (2012) 473e481.
[96] S.J. Lehotay, K. Mastovská, A.R. Lightfield, Use of buffering and other means to improve
results of problematic pesticides in a fast and easy method for residue analysis of fruits and
vegetables, J. AOAC Int. 88 (205) (2005) 615e629.
[97] A. Hiba, A. Carine, A.R. Haifa, L. Ryszard, J. Farouk, Monitoring of twenty-two sul-
fonamides in edible tissues: investigation of new metabolites and their potential toxicity,
Food Chem. 192 (2016) 212e227.
[98] Z. Zhang, H. Yan, F. Cui, H. Yun, X. Chang, J. Li, X. Liu, L. Yang, Q. Hu, Analysis of
multiple b-agonist and b-blocker residues in porcine muscle using improved QuEChERS
method and UHPLC-LTQ orbitrap mass spectrometry, Food Anal. Method. 9 (2016) 915e924.
[99] Official Journal of the European Union, L15 20 January 2010, Commission Regulation
(EU) No 37/2010 of 22 December 2009 on Pharmacologically Active Substances and Their
Classification Regarding Maximum Residue Limits in Foodstuffs of Animal Origin, 2009.
Brussels, Belgium.
[100] Y. Zhang, X. Liu, X. Li, J. Zhang, Y. Cao, M. Su, Z. Shi, H. Sun, Rapid screening and
quantification of multi-class multi-residue veterinary drugs in royal jelly by ultra perfor-
mance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry,
Food Control 60 (2016) 667e676.
[101] D. Pimentel-Trapero, A. Sonseca-Yepes, S. Moreira-Romero, M. Hernández-Carrasquilla,
Determination of macrocyclic lactones in bovine liver using QuEChERS and HPLC with
fluorescence detection, J. Chromatogr. B 1015e1016 (2016) 166e172.
[102] V. Gressler, A.R.L. Franzen, G.J.M.M. de Lima, F.C. Tavernari, O.A. Dalla Costa,
V. Feddern, Development of a readily applied method to quantify ractopamine residue in
meat and bone meal by QuEChERS-LC-MS/MS, J. Chromatogr. B 1015e1016 (2016)
192e200.
[103] J. Li, J. Zhang, H. Liu, L. Wu, A comparative study of primary secondary amino (PSA) and
multi-walled carbon nanotubes (MWCNTs) as QuEChERS absorbents for the rapid
determination of diazepam and its major metabolites in fish samples by high-performance
liquid chromatography-electrospray ionisation-tandem mass spectrometry, J. Sci. Food
Agric. 96 (2016) 555e560.
[104] M. Lombardo-Agüı́, L. Gámiz-Gracia, C. Cruces-Blanco, A.M. Garcı́a-Campaña, Com-
parison of different sample treatments for the analysis of quinolones in milk by capillary-
liquid chromatography with laser induced fluorescence detection, J. Chromatogr. A 1218
(2011) 4966e4971.
ARTICLE IN PRESS
[105] A. Martı́nez-Villalba, E. Moyano, M.T. Galcerán, Ultra-high performance liquid chro-

matography-atmospheric pressure chemical ionization-tandem mass spectrometry for the
analysis of benzimidazole compounds in milk samples, J. Chromatogr. A 1313 (2013)
119e131.
[106] A. Martı́nez-Villalba, L. Vaclavik, E. Moyano, M.T. Galcerán, J. Hajslova, Direct
analysis in real time high-resolution mass spectrometry for high-throughput analysis of
antiparasitic veterinary drugs in feed and food, Rapid Commun. Mass Spectrom. 27
(2013) 467e475.
[107] F. Plössl, M. Giera, F. Bracher, Multiresidue analytical method using dispersive solid-
phase extraction and gas chromatography/ion trap mass spectrometry to determine phar-
maceuticals in whole blood, J. Chromatogr. A 1135 (2006) 19e26.
[108] Y. Li, S. Wen, Z. Chen, Z. Xiao, M. Ma, Ultra-high performance liquid chromatography
tandem mass spectrometry for simultaneous analysis of aflatoxins B1, G1, B2, G2, zear-
alenone and its metabolites in eggs using a QuEChERS based extraction procedure, Anal.
Methods 7 (2015) 4145e4151.
[109] O. Núñez, H. Gallart-Ayala, C.P.B. Martins, P. Lucci, New trends in fast liquid chroma-
tography for food and environmental analysis, J. Chromatogr. A 1228 (2012) 298e323.
[110] V.L. Pereira, J.O. Fernandes, S.C. Cunha, Comparative assessment of three cleanup pro-
cedures after QuEChERS extraction for determination of trichothecenes (type A and type
B) in processed cereal-based baby foods by GC-MS, Food Chem. 182 (2015) 143e149.
[111] Y. Rodrı́guez-Carrasco, G. Font, J.C. Moltó, H. Berrada, Quantitative determination of
trichothecenes in breadsticks by gas chromatography-triple quadrupole tandem mass
spectrometry, Food Addit. Contam. Part A 31 (2014) 1422e1430.
[112] Y. Rodrı́guez-Carrasco, J.C. Moltó, H. Berrada, J. Mañes, A survey of trichothecenes,
zearalenone and patulin in milled grain-based products using GC-MS/MS, Food Chem.
146 (2014) 212e219.
[113] U. Koesukwiwat, K. Sanguankaew, N. Leepipatpiboon, Evaluation of a modified
QuEChERS method for analysis of mycotoxins in rice, Food Chem. 153 (2014) 44e51.
[114] L. Vaclavik, M. Zachariasova, V. Hrbek, J. Hajslova, Analysis of multiple mycotoxins in
cereals under ambient conditions using direct analysis in real time (DART) ionization
coupled to high resolution mass spectrometry, Talanta 82 (2010) 1950e1957.
[115] N. Michlig, M.R. Repetti, C. Chiericatti, S.R. Garcı́a, M. Gaggiotti, J.C. Bası́lico,
H.R. Beldoménico, Multiclass compatible sample preparation for UHPLC-MS/MS
determination of aflatoxin M1 in raw milk, Chromatographia 79 (2016) 1091e1100.
[116] Y. Rodrı́guez-Carrasco, M. Fattore, S. Albrizio, H. Berrada, J. Mañes, Occurrence of
fusarium mycotoxins and their dietary intake through beer consumption by the European
population, Food Chem. 178 (2015) 149e155.
[117] J. Taibon, S. Sturm, C. Seger, H. Strasser, H. Stuppner, Quantitative assessment of des-
truxins from strawberry and maize in the lower parts per billion range: combination of a
QuEChERS based extraction protocol with a fast and selective UHPLC-QTOF-MS assay,
J. Agric. Food Chem. 63 (2015) 5707e5713.
[118] S. Zhang, J. Lu, S. Wang, D. Mao, S. Miao, S. Ji, Multi-mycotoxins analysis in Pheretima
using ultra-high-performance liquid chromatography tandem mass spectrometry based on
a modified QuEChERS method, J. Chromatogr. B 1035 (2016) 31e41.
[119] Z. Veprikova, M. Zachariasova, Z. Dzuman, A. Zachariasova, M. Fenclova, P. Slavikova,
M. Vaclavikova, K. Mastovská, D. Hengst, J. Hajslova, Mycotoxins in plant-based dietary
supplements: hidden health risk for consumers, J. Agric. Food Chem. 63 (2015)
6633e6643.
ARTICLE IN PRESS
[120] E.J. Llorent-Martı́nez, P. Ortega-Barrales, M.L. Fernández-de Córdova, A. Ruiz-Medina,

Quantitation of ochratoxin A in cereals and feedstuff using sequential injection analysis
with luminescence detection, Food Control 30 (2013) 379e385.
[121] United States Environmental Protection Agency (U.S. EPA), Appendix A to 40 CFR Part 423,
U.S. EPA, Washington, D.C, 2010. http://www.epa.gov/waterscience/methods/pollutants.html.
[122] A.O. Oduntan, N.T. Tavengwa, E. Cukrowska, S.D. Mhlanga, L. Chimuka, QuEChERS
method development for bio-monitoring of low molecular weight polycyclic aromatic
hydrocarbons in South African carp fish using HPLC-fluorescence: an initial assessment,
S. Afr. J. Chem. 69 (2016) 98e104.
[123] T.V. Madureira, S. Velhote, C. Santos, C. Cruzeiro, E. Rocha, M.J. Rocha, A step for-
ward using QuEChERS (quick, easy, cheap, effective, rugged, and safe) based extraction
and gas chromatography-tandem mass spectrometry-levels of priority polycyclic aro-
matic hydrocarbons in wild and commercial mussels, Environ. Sci. Pollut. Res. 21
(2014) 6089e6098.
[124] M. Surma, A.S. Rociek, E. Cieslik, The application of d-SPE in the QuEChERS method
for the determination of PAHs in food of animal origin with GC-MS detection, Eur. Food
Res. Technol. 238 (2014) 1029e1036.
[125] M. Yoo, S. Lee, S. Kim, S.-J. Kim, H.-Y. Seo, D. Shin, A comparative study of the
analytical methods for the determination of polycyclic aromatic hydrocarbons in seafood
by high-performance liquid chromatography with fluorescence detection, Int. J. Food Sci.
Tech. 49 (2014) 1480e1489.
[126] T.H. Kao, S. Chen, C.W. Huang, C.J. Chen, B.H. Chen, Occurrence and exposure to
polycyclic aromatic hydrocarbons in kindling-free-charcoal grilled meat products in
Taiwan, Food Chem. Toxicol. 71 (2014) 149e158.
[127] A.L.V. Escarrone, S.S. Caldas, E.B. Furlong, V.L. Meneghetti, C.A.A. Fagundes,
J.L.O. Arias, E.G. Primel, Polycyclic aromatic hydrocarbons in rice grain dried by
different processes: evaluation of a quick, easy, cheap, effective, rugged and safe extraction
method, Food Chem. 146 (2014) 597e602.
[128] S. Chen, T.H. Kao, C.J. Chen, C.W. Huang, B.H. Chen, Reduction of carcinogenic
polycyclic aromatic hydrocarbons in meat by sugar-smoking and dietary exposure
assessment in Taiwan, J. Agric. Food Chem. 61 (2013) 7645e7653.
[129] G. Knobel, A.D. Campiglia, Determination of polycyclic aromatic hydrocarbon metabo-
lites in milk by a quick, easy, cheap, effective, rugged and safe extraction and capillary
electrophoresis, J. Sep. Sci. 36 (2013) 2291e2298.
[130] S.-S. Cai, J. Stevens, J.A. Syage, Ultra high performance liquid chromatography-atmo-
spheric pressure photoionization-mass spectrometry for high-sensitivity analysis of US
Environmental Protection Agency sixteen priority pollutant polynuclear aromatic hydro-
carbons in oysters, J. Chromatogr. A 1227 (2012) 138e144.
[131] A. Angioni, L. Porcu, M. Secci, P. Addis, QuEChERS method for the determination of
PAH compounds in sardinia sea urchin (Paracentrotus lividus) Roe, using gas chroma-
tography ITMS-MS analysis, Food Anal. Method. 5 (2012) 1131e1136.
[132] T.H. Kao, S. Chen, C.J. Chen, C.W. Huang, B.H. Chen, Evaluation of analysis of poly-
cyclic aromatic hydrocarbons by the QuEChERS method and gas chromatography-mass
spectrometry and their formation in poultry meat as affected by marinating and frying, J.
Agric. Food Chem. 60 (2012) 1380e1389.
[133] N.D. Forsberg, G.R. Wilson, K.A. Anderson, Determination of parent and substituted
polycyclic aromatic hydrocarbons in high-fat salmon using a modified QuEChERS
extraction, dispersive SPE and GC-MS, J. Agric. Food Chem. 59 (2011) 8108e8116.
ARTICLE IN PRESS
[134] M. Smoker, K. Tran, R.E. Smith, Determination of polycyclic aromatic hydrocarbons

(PAHs) in shrimp, J. Agric. Food Chem. 58 (2010) 12101e12104.
[135] M.J. Ramalhosa, P. Paı́ga, S. Morais, C. Delerue-Matos, M.B.P.P. Oliveira, Analysis of
polycyclic aromatic hydrocarbons in fish: evaluation of a quick, easy, cheap, effective,
rugged, and safe extraction method, J. Sep. Sci. 32 (2009) 3529e3538.
[136] M. Bustamante-Rangel, M.M. Delgado-Zamarreño, L. Pérez-Martı́n, R. Carabias-Martı́nez,
QuEChERS method for the extraction of isoflavones from soy-based foods before deter-
mination by capillary electrophoresis-electrospray ionization-mass spectrometry, Micro-
chem. J. 108 (2013) 203e209.
[137] J. Domı́nguez-Álvarez, E. Rodrı́guez-Gonzalo, J. Hernández-Méndez, R. Carabias-Martı́nez,
Programed nebulizing-gas pressure mode for quantitative capillary electrophoresis-mass
spectrometry analysis of endocrine disruptors in honey, Electrophoresis 33 (2012)
2374e2381.
[138] J. de Boer, M. Wagelmans, Polycyclic aromatic hydrocarbons in soil-practical options for
remediation, Clean-Soil Air Water 44 (2016) 648e653.
[139] K. Srogi, Monitoring of environmental exposure to polycyclic aromatic hydrocarbons: a
review, Environ. Chem. Lett. 5 (2007) 169e195.
[140] M.M. Plassmann, M. Schmidt, W. Brack, M. Krauss, Detecting a wide range of envi-
ronmental contaminants in human blood samples-combining QuEChERS with LC-MS and
GC-MS methods, Anal. Bioanal. Chem. 407 (2015) 7047e7054.
[141] V. Homem, E. Silva, A. Alves, L. Santos, Scented traces e dermal exposure of synthetic
musk fragrances in personal care products and environmental input assessment, Chemo-
sphere 139 (2015) 276e287.
[142] Y. Sapozhnikova, S.J. Lehotay, Multi-class, multiresidue analysis of pesticides,
polychlorinated biphenyls, polycyclic aromatic hydrocarbons, PBDEs and novel flame
retardants in using fast, low-pressure gas chromatography-tandem mass spectrometry,
Anal. Chim. Acta 758 (2013) 80e92.
[143] M. Surma, W. Wiczkowski, E. Cieslik, H. Zieli nski, Method development for the
determination of PFOA and PFOS in honey based on the dispersive solid phase extraction
(d-SPE) with micro-UHPLC-MS/MS system, Microchem. J. 121 (2015) 150e156.
[144] S. Song, X. Dai, W. Wang, Y. He, Z. Liu, M. Shao, Optimization of selective pressurized
liquid extraction and ultrasonication-assisted QuEChERS methods for the determination of
polybrominated diphenyl ethers in sediments, Anal. Methods 7 (2015) 9542e9548.
[145] Z. He, L. Wang, Y. Peng, M. Luo, W. Wang, X. Liu, Determination of selected poly-
chlorinated biphenyls in soil and earthworm (Eisenia fetida) using a QuEChERS-based
method and gas chromatography with tandem MS, J. Sep. Sci. 38 (2015) 3766e3773.
[146] J. Camilleri, E. Vulliet, Determination of steroid hormones in sediments based on quick,
easy, cheap, effective, rugged, and safe (modified-QuEChERS) extraction followed by
liquid chromatography-tandem mass spectrometry (LC-MS/MS), Anal. Methods 7 (2015)
9577e9586.
[147] R. Shuiying, W. Hongfei, F. Shun, W. Jide, L. Yi, Determination of 21 plant growth
regulators in tomatoes using an improved ultrasound-assisted QuEChERS technique
combined with a liquid chromatography tandem mass spectrometry method, Anal.
Methods 8 (2016) 4808e4815.
[148] M. Mattarozzi, M. Milioli, F. Bianchi, A. Cavazza, S. Pigozzi, A. Milandri, M. Careri,
Optimization of a rapid QuEChERS sample treatment method for HILIC-MS2 analysis
of paralytic shellfish poisoning (PSP) toxins in mussels, Food Control 60 (2016)
138e145.
ARTICLE IN PRESS
[149] A. Rúbies, E. Muñoz, D. Gibert, N. Cortés-Francisco, M. Granados, J. Caixach,

F. Centrich, New method for the analysis of lipophilic marine biotoxins in fresh and
canned bivalves by liquid chromatography coupled to high resolution mass spectrometry: a
quick, easy, cheap, efficient, rugged, safe approach, J. Chromatogr. A 1386 (2015) 62e73.
[150] S.J. Lehotay, Y. Sapozhnikova, L. Han, J.J. Johnston, Analysis of nitrosamines in cooked
bacon by QuEChERS sample preparation and gas chromatographytandem mass spec-
trometry with backflushing, J. Agric. Food Chem. 63 (2015) 10341e10351.
[151] Z. Xun, J. Huang, X.Y. Li, S. Lin, S. He, X. Guo, Y. Xian, Simultaneous determination of
seven acrylates in food contact paper products by GC/MS and modified QuEChERS, Anal.
Methods 8 (2016) 3953e3958.
[152] Y. Ruiz-Garcı́a, C.L. Silva, E. Gómez-Plaza, J.S. Câmara, A powerful analytical strategy
based on QuEChERS-dispersive solid-phase extraction combined with ultrahigh pressure
liquid chromatography for evaluating the effect of elicitors on biosynthesis of trans-
resveratrol in grapes, Food Anal. Method. 9 (2016) 670e679.
[153] M. Mülek, P. Högger, Highly sensitive analysis of polyphenols and their metabolites in
human blood cells using dispersive SPE extraction and LC-MS/MS, Anal. Bioanal. Chem.
407 (2015) 1885e1899.
[154] D.Y. Bang, S.K. Byeon, M.H. Moon, Rapid and simple extraction of lipids from blood
plasma and urine for liquid chromatography-tandem mass spectrometry, J. Chromatogr. A
1331 (2014) 19e26.
[155] Y. Ma, Y. Hashi, F. Ji, J.M. Li, Determination of phthalates in fruit jellies by dispersive
SPE coupled with HPLC-MS, J. Sep. Sci. 33 (2010) 251e257.
[156] K. Hasegawa, A. Wurita, K. Minakata, K. Gonmori, I. Yamagishi, K. Watanabe, O. Suzuki,
Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body
fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection
of the drugs in unchanged forms, Forensic Toxicol. 33 (2015) 45e53.
[157] C.L. Fan, Q.Y. Chang, Z.Y. Li, J. Kang, G.Q. Pan, S.Z. Zheng, W.W. Wang, C.C. Yao,
X.X. Ji, High-throughput analytical techniques for determination of residues of 653
multiclass pesticides and chemical pollutants in tea, part II: comparative study of
extraction efficiencies of three sample preparation techniques, J. AOAC Int. 96 (2013)
432e440.
[158] E. Vulliet, A. Berloiz-Barbier, F. Lafay, R. Baudot, L. Wiest, A. Vauchez, F. Lestremau,
F. Botta, C. Cren-Olivé, A national reconnaissance for selected organic micropollutants in
sediments on French territory, Environ. Sci. Pollut. Res. Int. 21 (2014) 11370e11379.
[159] A. Wurita, K. Hasegawa, K. Minakata, K. Gonmori, H. Nozawa, I. Yamagishi, O. Suzuki,
K. Watanabe, Postmortem distribution of a-pyrrolidinobutiophenone in body fluids and
solid tissues of a human cadaver, Leg. Med. 16 (2014) 241e246.
[160] A.R. Fontana, R. Bottini, QuEChERS method for the determination of 3-alkyl-2-
methoxypyrazines in wines by gas chromatography-mass spectrometry, Food Anal.
Method 9 (2016) 3352e3359.
[161] R.P.Z. Furlani, F.F.G. Dias, P.M. Nogueira, F.M.L. Gomes, S.A.V. Tfouni,
M.C.R. Camargo, Occurrence of macrocyclic lactones in milk and yogurt from Brazilian
market, Food Control 48 (2015) 43e47.
[162] W. Jia, Y. Ling, Y. Lin, J. Chang, X. Chu, Analysis of additives in dairy products by liquid
chromatography coupled to quadrupole-orbitrap mass spectrometry, J. Chromatogr. A
1336 (2014) 67e75.
[163] M. Faraji, M. Noorani, B.N. Sahneh, Quick, easy, cheap, effective, rugged, and safe
method followed by ionic liquid-dispersive liquid-liquid microextraction for the
ARTICLE IN PRESS
determination of trace amount of bisphenol A in canned foods, Food Anal. Method (2016).
http://dx.doi.org/10.1007/s12161-016-0635-y.
[164] H. Gallart-Ayala, O. Núñez, E. Moyano, M.T. Galcerán, Analysis of UV ink photoinitiators
in packaged food by fast liquid chromatography at sub-ambient temperature coupled to
mass spectrometry, J. Chromatogr. A 1218 (2011) 459e466.
[165] O.G. Cabrices, A. Schreiber, W.E. Brewer, Automated sample preparation and analysis
workflows for pesticide residue screenings in food samples using DPX-QuEChERS with LC/
MS/MS, Gerstel AppNote 8/2013. http://www.gerstel.com/pdf/p-lc-an-2013-08.pdf.
[166] P. Kaewsuya, W.E. Brewer, J. Wong, S.L. Morgan, Automated QuEChERS tips for anal-
ysis of pesticide residues in fruits and vegetables by GC-MS, J. Agric. Food Chem. 61
(2013) 2299e2314.
[167] S.J. Lehotay, L. Han, Y. Sapozhnikova, Automated mini-column solid-phase extraction
cleanup for high-throughput analysis of chemical contaminants in foods by low-pressure
gas chromatographydtandem mass spectrometry, Chromatoraphia 79 (2016) 1113e1130.
[168] S. Ferhi, M. Bourdat-Deschamps, J.-J. Daudin, S. Houot, S. Nélieu, Factors influencing the
extraction of pharmaceuticals from sewage sludge and soil: an experimental design
approach, Anal. Bioanal. Chem. 408 (2016) 6153e6168.
[169] Teledyne Tekman. http://www.teledynetekmar.com/products/semi-volatile-organic-
compounds-(svoc)/automate-q40.
[170] T. Trent, Pesticide analysis using the AutoMate-Q40: an automated solution to QuEChERS
extractions, LC-GC N. Am. 25 (June 1, 2013). The application notebook.
[171] T. Trent, Veterinary drug residue analysis using the AutoMate-Q40: an automated solution
to QuEChERS, LC-GC N. Am. 24 (June 1, 2014). The application notebook.
[172] T. Trent, Determination of carbendazim in orange juice using an automated QuEChERS
solution, LC GC N. Am. 26 (September 1, 2014).

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ARTICLE IN PRESS

Recent Advances and

Glossary CEN European Committee for

Comprehensive Analytical Chemistry, Vol. 76. http://dx.doi.org/10.1016/bs.coac.2017.01.008

2 Comprehensive Analytical Chemistry

ECD Electron capture detector. OCP Organochlorine pesticide.

Advances and Developments in the QuEChERS Method Chapter j 3

disciplines of chemistry and the application of innovative scientific solutions

4 Comprehensive Analytical Chemistry

organizations (the European Union [14] and AOAC International [15]) to

Advances and Developments in the QuEChERS Method Chapter j 5

without PSA Cleanup with PSA SPE Cleanup

6 Comprehensive Analytical Chemistry

Advances and Developments in the QuEChERS Method Chapter j 7

FIGURE 2 Effect of pH on the presence of matrix coextractives in GCeMS chromatograms (full

8 Comprehensive Analytical Chemistry

provide an additional cleanup. As a result, PSA was initially selected as

2. MODIFICATIONS OF THE ORIGINAL METHOD

Advances and Developments in the QuEChERS Method Chapter j 9

Anastassiades et al., 2003 Original

10 Comprehensive Analytical Chemistry

2.2 Extraction Solvent

2.3 Dispersive Solid-Phase Extraction Sorbents

Advances and Developments in the QuEChERS Method Chapter j 11

2.4 Salt Addition

12 Comprehensive Analytical Chemistry

2.5 Freezing of the Sample or Introduction of a Freezing-Out

Advances and Developments in the QuEChERS Method Chapter j 13

Advances and Developments in the QuEChERS Method Chapter j 19

the conventional one, including problematic pesticides with pH dependency

20 Comprehensive Analytical Chemistry

3.2 Pharmaceutical Analysis

22 Sulfonamides Chicken, 10 mL ACN 4 g MgSO4, 900 mg LCeMS/MS e e 2 mL of water [97]

26 Veterinary Pork 20 mL 4 g MgSO4, 40 mg PSA, HPLCeMS/ 61e106 0.01e Comparison of [32]

Advances and Developments in the QuEChERS Method Chapter j 25

3.3 Mycotoxin Analysis

Advances and Developments in the QuEChERS Method Chapter j 27

exposure. However, as it is shown in Table 3, in which the applications

3 Mycotoxins Pomegranate 15 mL ACN 4 g MgSO4, 600 mg HPLCeDAD 82e108 15e20 e [67]

Advances and Developments in the QuEChERS Method Chapter j 31

injection analysis with fluorescence detector or terbium-sensitized lumines-

3.4 Polycyclic Aromatic Hydrocarbon Analysis

Advances and Developments in the QuEChERS Method Chapter j 35

36 Comprehensive Analytical Chemistry

Advances and Developments in the QuEChERS Method Chapter j 37

9 Siloxanes Pine needles, 10 mL 6 g MgSO4, 900 mg GCeMS 56e63 1.845e e [35]

42 Comprehensive Analytical Chemistry

Advances and Developments in the QuEChERS Method Chapter j 43

comparable results in terms of efficiency, speed, solvent and reagent con-

4. CONCLUSIONS AND FUTURE TRENDS

44 Comprehensive Analytical Chemistry

substances and to the demonstrated efficiency of QuEChERS, it would not be

Advances and Developments in the QuEChERS Method Chapter j 45

[5] A. Gałuszka, P. Konieczka, Z.M. Migaszewski, J. Namiesnik, Analytical eco-scale for

46 Comprehensive Analytical Chemistry

Advances and Developments in the QuEChERS Method Chapter j 47

[34] X. Xu, X. Zhang, E. Duhoranimana, Y. Zhang, P. Shu, Determination of methenamine

48 Comprehensive Analytical Chemistry

[49] S. Walorczyk, D. Dro_zd_zynski, R. Kierzek, Two-step dispersive-solid phase

Advances and Developments in the QuEChERS Method Chapter j 49

50 Comprehensive Analytical Chemistry

[77] G. Ramadan, M. Al Jabir, N. Alabdulmalik, A. Mohammed, Validation of a method for the

Advances and Developments in the QuEChERS Method Chapter j 51

microextraction and stacking before micellar electrokinetic chromatography, Anal.