Recent Advances and Developments in the QuEChERS Method

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Recent Advances and Developments in the QuEChERS Method Ba´rbara Socas-Rodrı´guez, Javier Gonza´lez-Sa´lamo, Antonio V. Herrera-Herrera, Javier Herna´ndez-Borges and Miguel A´. Rodrı´guez-Delgado1 Universidad de La Laguna (ULL), San Cristo´bal de La Laguna, Spain 1 Corresponding author: E-mail: [email protected]

Chapter Outline 1. Introduction 2. Modifications of the Original Method 2.1 pH Adjustment 2.2 Extraction Solvent 2.3 Dispersive Solid-Phase Extraction Sorbents 2.4 Salt Addition 2.5 Freezing of the Sample or Introduction of a FreezingOut Step Glossary

ACN Acetonitrile. Al-N Alumina neutral. AOAC Association of Analytical Communities. ASE Accelerated solvent extraction. BSA Bis-(trimethylsilyl)acetamide. C18 Octadecylsilane. CCa Limit of decision. CCb Detection capability. CE Capillary electrophoresis.

2 8 8 10 10 11

3. Application Fields 3.1 Pesticide Analysis 3.2 Pharmaceutical Analysis 3.3 Mycotoxin Analysis 3.4 Polycyclic Aromatic Hydrocarbon Analysis 3.5 Miscellaneous 4. Conclusions and Future Trends Acknowledgements References

13 13 20 25 31 37 43 44 44

12 CEN European Committee for Standardization. CLC Capillary liquid chromatography. DAD Diode array detector. DART Direct analysis in real time. DCM Dichloromethane. di-Na Sodium citrate dibasic sesquihydrate. DLLME Dispersive liquideliquid microextraction. d-SPE Dispersive solid-phase 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.

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ARTICLE IN PRESS 2 Comprehensive Analytical Chemistry ECD Electron capture detector. EN European norm. EPA Environmental Protection Agency. EtOAc Ethyl acetate. EU European Union. EURL European Union Reference Laboratories. FA Fatty acid. FD Fluorescence detector. FIA Flow injection analysis. FID Flame ionization detector. GAC Green analytical chemistry. GC Gas chromatography. GCB Graphitized carbon black. HLB Hydrophilicelipophilic balance. HPLC High-performance liquid chromatography. IAC Immunoaffinity column. IL Ionic liquid. IS Internal standard. LC Liquid chromatography. LLE Liquideliquid extraction. LOD Limit of detection. LPGC Low-pressure gas chromatography. MeOH Methanol. MRL Maximum residue limit. MS Mass spectrometry. MSPD Matrix solid-phase dispersion. MWCNT Multiwalled carbon nanotube. Na2EDTA Disodium ethylenediaminetetraacetate. NaOAc Sodium acetate. NH4OAc Ammonium acetate. NPD Nitrogen phosphorus detector.

OCP Organochlorine pesticide. OH-PAH Monohydroxylated polycyclic aromatic hydrocarbon. PAH Polycyclic aromatic hydrocarbon. PBDE Polybrominated diphenyl ether. PBS Phosphate-buffered saline. PCB Polychlorinated biphenyl. PFC Perflourinated compound. PLE Pressurized liquid extraction. PSA N-propylethylendiamine. Q Single quadrupole. QAC Quaternary ammonium compound. QqQ Triple quadrupole. QTOF Quadrupole-time of flight. RSD Relative standard deviation. SAX Strong anion exchange. SFE Supercritical fluid extraction. SFO Solidification of floating organic drop. SLE Solideliquid extraction. SPE Solid-phase extraction. SVHC Substance of very high concern. TFA Trifluoroacetic acid. TMCS Trimethylchlorosilane. TMSI N-trimethylsilylimidazole. TOF Time of flight. TPP Triphenylphosphate. tri-Na Sodium citrate tribasic dihydrate. TSL Terbium-sensitized luminescence. UAE Ultrasound-assisted extraction. UFLC Ultra-fast-liquid chromatography. UHPLC Ultra-high-performance liquid chromatography. 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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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 chemistry 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]. However, 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 Anastassiades (visiting scientist from Chemisches und Veterina¨runtersuchungsamt, 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 efficiency 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 background in mass spectrometry (MS) chromatograms and matrix-induced chromatographic 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) applications. 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

Co-Extracted Matrix (mg/g)

without PSA Cleanup

with PSA SPE Cleanup

3.5 2.8 2.1 1.4 0.7 0 EtOAc

ACN ACN:Acetone Extraction Solvent

Acetone

FIGURE 1 Comparison of different solvents for the extraction of a mixture of fruits and vegetables 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 disadvantages (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 conglomerates. 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 interferences. 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 methacrylate-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-matrixmatched 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 largevolume 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 Quick Easy Cheap Effective Rugged Safe Formate buffer and others

Others: Florisil®, MWCNTs, Chlorofiltr®, etc.

Citrate buffer (EN 15662)

Use of GCB

9

Original QuEChERS method

10 g sample extraction with 10 mL ACN

Water addition

4 g MgSO4 and 1 g NaCl

Acetate buffer

d-SPE: 1 mL extract, 150 mg MgSO4 and 25 mg PSA

(samples with water content < 80%)

(AOAC 2007.01)

Use of C18 and Z-Sep or ZZep+

Sample freezing (thermolabile analytes)

Additional freeze-out step

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 pHcontrolled 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 determine 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 interactions between analytes and matrix ensuring a suitable partitioning in the first step. Beside this, a suitable selection of the organic solvent is crucial to guarantee 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 coextractive 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 ZSep 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 lipophilic 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, Gonza´lez-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 independently 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 samples] ensured a suitable pH for high recovery of most pesticides independently 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 performance 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 unnecessary 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 international 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 methodology [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], zirconium-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 conventional 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 Analytes

Sample (Amount)

58 Pesticides

Extraction

Analytical Method

Recovery (%)

LODs

Comments

References

4 g MgSO4, 1 g NaCl

900 mg MgSO4, 150 mg PSA, 150 mg C18

GCeMS/MS

69e119

0.03e1.5 mg/kg

10 mL of water was added initially. Real samples were analysed. Different cleanup sorbents were tested. Heptachlor epoxide was used as IS

[29]

20 mL ACN 1% acetic acid (v/v), 2 mL hexane

2 g NaCl

150 mg PSA, 50 mg C18

GCeECD

79e104

1.2e150 mg/kg

10 mL of water was added initially for dehydrated red pepper. Real samples were analysed

[73]

Beans, cabbage, beef, fish (10 g)

10 mL ACN

3 g MgSO4, 1.5 g NaCl

1.5 g MgSO4, 27.5 mg PSA

GCeECD

80e92

0.25e19.29 mg/kg

GCxGC-TOF-MS was used to confirm the identification of target compounds in samples. Real samples were analysed

[74]

Coconut pulp (10 g), coconut water (10 mL)

10 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 1.5 g NaOAc

600 mg MgSO4, 100 mg PSA, 500 mg C18

UHPLCeMS/ MS

70e120

3 mg/kg

Cooling of supernatant in a dry ice prior to the cleanup step

[75]

Salts

Soil (5 g)

10 mL ACN 1% acetic acid (v/v)

8 Pyrethroid pesticides

Green and red pepper (10 g), dehydrated red pepper (1 g)

11 OCPs

11 Pesticides

ARTICLE IN PRESS

Sorbents in the d-SPE Step

Solvents

Human milk (1 mL)

1 mL ACN 1% acetic acid (v/v)

0.4 g MgSO4, 0.1 g NaOAc

157 mg MgSO4, 9 mg PSA, 9 mg C18

GCeMS/MS

70e120

0.2e2 mg/kg

Freezing of supernatant at 20 C for 2 h prior to cleanup step TPP was used as IS

[76]

120 Pesticides

Apple, cucumber (10 g)

10 mL ACN

4 g MgSO4, 1 g NaCl, 0.5 g di-Na, 1 g tri-Na

900 mg MgSO4, 150 mg PSA

HPLCeMS/ MS

70e120

1.2e100 mg/kg

e

[77]

21 Pesticides

Olive and grapeseed oil (6 g)

20 mL ACN

8 g MgSO4, 2 g NaCl

0.5e3.5 g ZSep

HPLCeDAD

50e130

e

10 mL of water was added initially. An additional SPE step using C18 cartridges was carried out before d-SPE

[47]

4 Pesticides

Maize grain (5 g), maize straw (2 g), soil (5 g)

10 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 1 g NaCl

200 mg MgSO4, 25 mg C18

UHPLCeMS/ MS

80e110

1.8 mg/kg

2 mL of water was added initially

[41]

74 Pesticides

Orange juice (10 mL)

10 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 1.7 g NaOAc

150 mg MgSO4, 40 mg PSA

UHPLCeMS/ MS

70e118

3.0e7.6 mg/ kg

TPP was used as IS

[78]

116 Pesticides

Honey (5 g)

10 mL ACN:EtOAc 70/30 (v/v) 1% acetic acid (v/v)

4 g MgSO4, 1 g NaOAc

150 mg MgSO4, 50 mg PSA, 50 mg Florisil

UHPLCeMS/ MS

70e120

5 mg/kg

10 mL of water was added initially

[52]

Continued

ARTICLE IN PRESS

88 Pesticides

TABLE 1 Some Examples of the Application of the QuEChERS Method to the Analysis of Pesticidesdcont’d Analytes

Sample (Amount)

Extraction Solvents

Salts

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

Comments

References

Fruit, cereal, starch and milk baby food (15 g)

15 mL ACN 1% acetic acid (v/v)

6 g MgSO4, 1.5 g NaOAc

150 mg MgSO4, 50 mg PSA, 50 mg C18

GCeMS

70e120

10e50 mg/ kg

Comparison of dSPE cleanup step with DLLME. TPP was used as IS

[79]

28 Carbamate pesticides

Aromatic herb (1 g)

10 mL ACN

4 g MgSO4, 1 g NaCl

200 mg MgSO4, 200 mg C18

UHPLCeMS/ MS

72e99

0.6 mg/kg

Comparison with other d-SPE sorbents

[80]

30 Pesticides

Milk (20 mL)

16 mL ACN

8 g MgSO4, 2 g NaCl

125 mg PSA, 25 mg Z-Sep, 5 mg Z-Sepþ

HPLCeDAD

70e100 (for almost all pesticides)

0.02e0.06 mg/L

-

[48]

74 Pesticides

Medicinal plant (2 g)

20 mL hexane

2 g NaCl, 3 g NaOAc

50 mg MgSO4, 50 mg C18, 50 mg Florisil

GCeMS/MS

70e120

3 mg/kg

10 mL was added initially. Chlorpyrifos-d10 was used as IS

[31]

223 Pesticides

Tobacco (2 g)

20 mL ACN

4 g MgSO4, 1 g NaCl, 0.5 g di-Na, 1 g tri-Na

150 mg MgSO4, 25 mg PSA, 2.5 mg GCB

GCemECD/ NPD

71e120

1e1.2 mg/kg

2 mL of water was added initially. Comparison with MSPD and SLE methods. GCeMS/ MS was applied for confirmation studies. TPP was used as IS

[81]

ARTICLE IN PRESS

LODs

24 Pesticides

Grape (10 g)

10 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 1.7 g NaOAc

300 mg MgSO4, 100 mg PSA

UHPLCeMS/ MS

70e120

3 mg/kg

TPP was used as IS

[82]

171 Pesticides

Cowpea (10 g)

10 mL ACN

4 g MgSO4, 1 g NaCl

150 mg MgSO4, 5 mg MWCNTs

GCeMS/MS

74e129 (for almost all pesticides)

1e3 mg/kg

Comparison with PSA and C18 cleanup sorbents

[54]

400 Pesticides

Sugar beet, beet molasses (10 g)

10 mL ACN 1% formic acid (v/v)

4 g MgSO4, 1 g NaCl, 0.5 g di-Na, 1 g tri-Na

150 mg MgSO4, 25 mg PSA, 2.5 mg GCB

GCeMS/MS, HPLCeMS/ MS

60e140

5e10 mg/kg

5 mL of water was added initially for beet molasses samples. Freezing of supernatant at 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

[83]

13 OCPs

Fish (5 g)

10 mL ACN

4 g MgSO4, 1 g NaCl

50 mg PSA

GCeECD

88e121

0.65e1.58 mg/kg

DLLMEeSFO was integrated in the cleanup step to concentrate de extract

[84]

ARTICLE IN PRESS

66 Pesticides

Continued

TABLE 1 Some Examples of the Application of the QuEChERS Method to the Analysis of Pesticidesdcont’d Analytes

Sample (Amount)

19 Pesticides

Grape (10 g)

Extraction Solvents

Salts

10 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 1 g NaOAc

Analytical Method

Recovery (%)

LODs

Comments

References

300 mg MgSO4, 400 mg Florisil

GCeMS

95e102

6e12 mg/kg

Comparison with conventional QuEChERS. Quintozene and caffeine were used as ISs of method and instrumental, respectively.

[53]

ACN, acetonitrile; C18, octadecylsilane; DAD, diode array detector; di-Na, sodium citrate dibasic sesquihydrate; DLLME, dispersive liquideliquid microextraction; d-SPE, dispersive solidphase 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.

ARTICLE IN PRESS

Sorbents in the d-SPE Step

ARTICLE IN PRESS Advances and Developments in the QuEChERS Method Chapter j

19

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 indicating 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 inadequate 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-3,5dimethylphenyl-N-methylcarbamate [93], 4,40 -dichlorobenzophenone [94],

ARTICLE IN PRESS 20 Comprehensive Analytical Chemistry

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; nervousness, 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 approaches 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 multiresidue 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], antiparasitic [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 Analytes

Sample (Amount)

Solvents

Salts

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

LODs

Comments

References

Buckwheat, wheat, soy, buckwheat flour, buckwheat noodle, amaranth grain, chia seeds, peeled millet (5 g)

10 mL ACN 1% formic acid (v/v)

4 g MgSO4, 1 g NH4OAc

25 mg PSA, 25 mg GCB

UHPLCeMS/ MS

50e92

0.04e0.2 mg/kg

10 mL of water was added initially

[28]

10 Nonsteroidal antiinflammatory drugs

Milk (5 g)

10 mL ACN 5% acetic acid (v/v), 4 mL ascorbic acid 0.02 M, HCl 0.24 M

1 g NH4OAc, 5 g Na2SO4

1 g MgSO4, 150 mg C18

HPLCeMS/ MS

78e97

CCa: 0.4e1.5 mg/kg, CCb: 0.8e1.9 mg/kg

6 mL of water was added initially. Meloxicam-d3, niflumic acid13 C , flufenamic 6 acid-13 C6 and phenylbutazone13 C 12 were used as ISs. Comparison between QqQ and Q-Orbitrap MS was used

[40]

Continued

ARTICLE IN PRESS

Atropine, scopolamine

TABLE 2 Some Examples of the Application of the QuEChERS Method to the Analysis of Pharmaceuticalsdcont’d Extraction Analytes

Sample (Amount)

Solvents

Salts

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

Comments

References

Mussel (10 g)

10 mL ACN

4 g MgSO4, 1 g NaCl, 0.5 g di-Na, 1 g tri-Na

900 mg MgSO4, 150 mg PSA, 150 mg C18

HPLCeDAD

101

30 mg/kg

Study of the half-life of diflubenzuron in mussel

[23]

3 Ionophore antimicrobials

Poultry litter (5 g)

10 mL ACN

4 g MgSO4, 1 g NaCl

150 mg MgSO4, 25 mg Florisil

HPLCe MS/MS

70e120

w10 mg/kg

10 mL of water was added initially. Real samples were analysed. Nigericin was used as IS

[51]

14 b-Agonists, 2 b-blockers

Porcine muscle (3 g)

10 mL ACN 1% acetic acid (v/v)

3 g MgSO4, 0.5 g NaCl

150 mg C18

UHPLCeMS

67e121

0.17e1.67 mg/ kg

2 mL of water was added initially. Real samples were analysed

[98]

22 Sulfonamides

Chicken, beef and sheep meat (5 g)

10 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 1 g NaCl, 0.5 g di-Na, 1 g tri-Na

900 mg MgSO4, 150 mg PSA

LCeMS/MS

e

e

2 mL of water was added initially. Sulfamethoxazoled4 was used as IS

[97]

ARTICLE IN PRESS

LODs

Diflubenzuron

Royal jelly (1 g)

5 mL citric acid 0.1 M:Na2HPO4 0.2 M 8/5 (v/v), 20 mL ACN 5% acetic acid (v/v)

2 g NaCl, 2 g Na2SO4

200 mg NH2 sorbents

UHPLCeMS/ MS

70e120

0.07e6 mg/kg

Real samples were analysed

[100]

Methenamine

Pork muscle, liver and kidney tissues (2 g)

10 mL ACN, 5 mL hexane

4 g Na2SO4

50 mg PSA

HPLCeMS/ MS

87e110

1.5 mg/kg

Methenamine13 C 15 N was 6 4 used as IS

[34]

Abamectin, ivermectin, doramectin, moxidectin

Bovine liver (10 g)

10 mL ACN

4 g MgSO4, 1 g NaCl, 0.5 g di-Na, 1 g tri-Na

1 g MgSO4, 25 mg PSA, 200 mg C18

HPLCeFD

85e90

CCa: 23e127 mg/kg

Analytes were derivatized to be analysed by FD

[101]

Ractopamine

Pork feed (5 g)

10 mL ACN

4 g MgSO4, 1 g of NaCl, 0.5 g di-Na, 1 g tri-Na

900 mg MgSO4, 150 mg PSA, 150 mg C18

HPLCeMS/ MS

96e107

1.91 mg/kg

Sample was previously hydrolysed using a protease and b-glucuronidase enzyme. Isoxsuprine hydrochloride was used as IS

[102]

26 Veterinary drugs

Pork manure (2 g)

20 mL MeOH:ACN:0.1 M EDTA McIlvaine Buffer 12.5/37.5/50 (v/v/v)

4 g MgSO4, 1 g NaCl

40 mg PSA, 20 mg C18

HPLCeMS/ MS

61e106

0.01e 1.86 mg/kg

Comparison of d-SPE step with conventional HLB cartridges

[32]

Continued

ARTICLE IN PRESS

90 Veterinary drugs

TABLE 2 Some Examples of the Application of the QuEChERS Method to the Analysis of Pharmaceuticalsdcont’d Extraction Solvents

Salts

8 Sulfonamides

Chicken muscle and egg (5 g)

10 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 1 g NaOAc

Diazepam, nordiazepam, temazepam, oxazepam

Carp (2 g)

10 mL ACN

3 Veterinary antibiotics

Milk, honey (2 g)

11 Pharmaceuticals

Celery, lettuce (500 mg)

Analytes

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

LODs

Comments

References

Muscle: 300 mg ZSepþ, egg: 300 mg PSA

HPLCeFD

66e81

4.2e25.5 mg/kg

e

[45]

2 g MgSO4, 1 g NaCl

100 mg PSA

HPLCeMS/ MS

89e110

0.5 mg/kg

Comparison with MWCNTs as d-SPE sorbent

[103]

15 mL ACN 0.1% acetic acid (v/v)

4 g MgSO4, 1 g NaCl

900 mg Na2SO4, 500 mg C18, 500 mg ZSepþ

CLCeMS/MS

96e100

0.02e0.045 mg/ kg

e

[46]

7 mL Na2EDTA 150 mg/ L:ACN:MeOH 28.6/46.4/25.0 (v/v/v)

2 g Na2SO4, 0.5 g NaCl

225 mg Na2SO4, 12.5 mg PSA, 12.5 mg C18

HPLCe MS/MS

70e119

0.7e8 mg/kg

Comparison with ASE and UAE methods

[33]

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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Sample (Amount)

ARTICLE IN PRESS Advances and Developments in the QuEChERS Method Chapter j

25

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 recovery 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 chromatographic 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 exclusively 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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26 Comprehensive Analytical Chemistry 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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27

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 Extraction Analytes

Sample (Amount)

Solvents

Salts

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

LODs

Comments

References

0.031e5.4 mg/kg

Study of different cleanup sorbents. Real samples were analysed

[22]

e

[37]

Chinese herb (1 g)

5 mL PBS, 2.5 mL ACN 5% acetic acid (v/v)

2 g MgSO4, 0.5 g NaCl, 0.5 g tri-Na, 0.25 g di-Na

150 mg MgSO4, 150 mg C18

UHPLCeMS/MS

75e104

Patulin

Wheat tortilla (10 g)

10 mL ACN

4 g MgSO4, 1 g NaCl

1.2 g MgSO4, 400 mg PSA, 400 mg C18

HPLCeMS/MS

e

22 Mycotoxins

Medicinal earthworm (1 g)

15 mL ACN 15% formic acid (v/v)

4 g MgSO4, 1 g NaCl

900 mg MgSO4, 300 mg PSA, 900 mg C18, 60 mg GCB

UHPLCeMS/MS

73e105

0.05e10 mg/kg

Before cleanup step, sample was placed in an ice bath for 10 min. Atrazine-d5 and13Czearalenone were used as ISs

[118]

Aflatoxin M1

Defatted and whole milk (10 mL)

10 mL ACN 0.1% formic acid (v/v), 1 mL Na2EDTA 1M

4 g MgSO4, 1 g NaOAc

200 mg MgSO4, 67 mg PSA, 180 mg C18

UHPLCeMS/MS

70e95

0.002 mg/L

Comparison with IAC cleanup

[115]

7 Mycotoxins

Egg (2 g)

10 mL ACN 0.1% formic acid (v/v)

4 g MgSO4, 1 g NaCl

100 mg PSA, 100 mg C18

UHPLCeMS/MS

85e115

1e5 mg/kg

2 mL of water was added initially Real samples were analysed

[108]

0.2 mg/kg

ARTICLE IN PRESS

21 Mycotoxins

Beet (6 g)

5 mL formic acid 0.1% (v/v), 10 mL ACN 0.1% formic acid (v/v)

4 g MgSO4, 1 g NaCl, 1 g tri-Na, 0.5 g di-Na

150 mg MgSO4, 25 mg PSA, 7.5 mg GCB

HPLCeMS/MS

64e168 (21 and 34 for gliotoxin and roquefortine C)

e

Real samples were analysed

[42]

10 Mycotoxins

Wheat, maize, rice (7.5 g)

15 mL ACN 1% acetic acid (v/v)

5.5 g MgSO4, 1.4 NaCl, 1 g tri-Na, 0.5 g di-Na

2 g MgSO4, 337 mg C18

HPLCeMS/MS

87e106

0.062e199 mg/kg

10 mL of water was added initially. Real samples were analysed

[39]

14 Mycotoxins

Beer (10 mL)

5 mL ACN

4 g MgSO4, 1 NaCl

900 mg MgSO4, 300 mg C18

GCeMS/MS

70e110

0.05e8 mg/L

Analytes were derivatized to be analysed by GCeMS/MS. Real samples were analysed

[116]

3 Mycotoxins

Pomegranate fruit (2 g) and juice (2 mL)

15 mL ACN 1% acetic acid (v/v), 7 mL cold water

4 g MgSO4, 1 NaCl

600 mg MgSO4, 200 mg PSA

HPLCeDAD

82e108

15e20 mg/kg

e

[67]

12 Mycotoxins

Cereal baby food (2.5 g)

10 mL ACN

4 g MgSO4, 1 NaCl

1.350 g MgSO4, 450 mg PSA

GCeMS

44e135

0.37e19.19 mg/kg

15 mL of water was added initially. a-Chloralose and 13 C15 deoxynivalenol was used as IS Comparison with MultiSep cleanup columns and IAC

[110]

Continued

ARTICLE IN PRESS

9 Mycotoxins

TABLE 3 Some Examples of the Application of the QuEChERS Method to the Analysis of Mycotoxinsdcont’d Extraction Analytes

Sample (Amount)

Solvents

Salts

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

Comments

References

10 mL of water was added initially. Roxithromycin 4 was used as IS.

[117]

e

[119]

3 Mycotoxins

Strawberry plant (10 g), maize plant (5 g)

10 mL ACN

6 g MgSO4, 1 g NaCl, 1 g tri-Na, 0.5 g di-Na

855 mg MgSO4, 150 mg PSA, 45 mg GCB

UHPLCeQTOFMS

55e106

0.6e0.96 mg/kg

57 Mycotoxins

Plant-based dietary supplement (1 g)

10 mL formic acid 1% (v/v), 10 mL ACN

4 g MgSO4, 1 g NaCl

300 mg MgSO4, 100 mg C18

UHPLCeMS/MS

40e122

1.5e300 mg/ kg

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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LODs

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31

injection analysis with fluorescence detector or terbium-sensitized luminescence [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 environmental 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, acenaphthylene, anthracene, benzo[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, 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 Analytes

Sample (Amount)

16 PAHs

Extraction

Analytical Technique

Recovery (%)

8 g MgSO4, 2 g NaCl

150 mg MgSO4, 50 mg diatomaceous earth

GCeMS/MS

10 mL acetone

6 g MgSO4, 1.5 g NaCl

1.8 g MgSO4, 400 mg PSA

Smoked fish (5 g)

10 mL ACN

4 g MgSO4, 1 g NaCl

5 PAHs

Carp fish (2.5 g)

10 mL ACN

16 PAHs

Wild and commercial mussels (10 g)

10 mL ACN

Salts

LODs

Comments

References

Soil (10 g)

30 mL ACN:H2O 2/1 (v/v)

81e110

0.39e1.53 mg/kg

A mixture hexane:H2O was also tested. PSA, C18, Florisil and clinoptilolite were also tried as cleanup sorbents. Acenaphthened10 and perylene-d12 as IS

[58]

Benzo[a] pyrene

Bread (5 g)

GCeMS/MS

97e120

0.3 mg/kg

5 mL of deionized water was added initially. Anthracene-d10 as IS

[30]

13 PAHs

900 mg MgSO4, 300 mg PSA, 150 mg C18

GCeFID

72e90

1.1e5.5 mg/kg

e

[38]

2 g MgSO4, 0.5 g NaCl

2 g MgSO4, 150 mg PSA

HPLCeFD

e

e

Comparative with Soxhlet was developed. Some different sorbents were tried

[122]

4 g MgSO4, 1 g NaCl

900 mg MgSO4, 150 mg PSA

GCeMS/MS

89e112

0.01e0.99 mg/L

5 deuterated as ISs

[123]

ARTICLE IN PRESS

Sorbents in the d-SPE Step

Solvents

Ham (8 g)

10 mL EtOAc

4 g MgSO4, 1 g NaCl

900 mg MgSO4, 150 mg PSA, 300 mg C18

GCeMS

72e111

0.1e1 mg/kg

Anthracene-d10 as IS

[124]

14 PAHs

Manila clams, hard clams, oysters, cockles (2 g)

5 mL ACN

2 g MgSO4, 0.5 g NaCl

150 mg MgSO4, 50 mg PSA

HPLCeFD

87e116

0.0500e0.5270 mg/kg

Extraction step was carried out twice

[125]

12 PAHs

Tea (1 g)

10 mL ACN

4 g MgSO4, 1 g NaCl

900 mg MgSO4, 150 mg PSA, 150 mg SAX

GCeMS

50e120

e

10 mL boiling water was added initially. One deuterated IS. LLE step after QuEChERS

[59]

16 PAHs

Kindling-freecharcoal grilled poultry meat, red meat, seafood (5 g)

10 mL ACN

6 g MgSO4, 1.5 g NaOAc

1200 mg MgSO4, 400 mg PSA, 400 mg C18 silica gel particles

GCeMS

71e104

0.1e2 mg/Lb

10 mL of water was added initially. Commercial QuEChERS kits

[126]

16 PAHs

Rice grain (10 g)

10 mL ACN 1% acetic acid (v/v)

6 g MgSO4, 1.5 g NaOAc

150 mg MgSO4, 50 mg PSA

GCeMS

70e122

e

10 mL of water was added initially. Six deuterated ISs

[127]

16 PAHs

Meat (5 g)

10 mL ACN

6 g MgSO4, 1.5 g NaOAc

1200 mg MgSO4, 400 mg PSA, 400 mg C18

GCeMS

71e104

0.1e2 mg/Lb

10 mL of water was added initially. Commercial QuEChERS kits

[128]

5 OHPAHs

Milk (1200 mL)

300 mL ACN

480 mg MgSO4, 120 mg NaCl

30 mg PSA, 30 mg C18

CEeUV

80e105

0.98e3.72 mg/kg

Hydrolysis step prior to QuEChERS

[129]

Continued

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12 PAHs

TABLE 4 Some Examples of the Application of the QuEChERS Method to the Analysis of PAHsdcont’d Extraction Solvents

Salts

Sorbents in the d-SPE Step

Analytical Technique

Recovery (%)

LODs

Comments

References

16 PAHs

Oysters (10 g)

15 mL ACN

6 g MgSO4, 1.5 g NaCl

150 mg MgSO4, 50 mg PSA

UHPLCeMS

71e110

13e129 mg/kg

7 mL of water was added initially. Commercial QuEChERS kits

[130]

17 PAHs

Sea urchin (1 g)

1 mL ACN

600 mg MgSO4, 150 mg NaOAc

90 mg MgSO4, 30 mg PSA, 15 mg C18

GCeMS/MS

70e120a

0.7e1.5 mg/kgb

e

[131]

16 PAHs

Chicken and duck meat (5 g)

10 mL ACN

6 g MgSO4, 1.5 g NaOAc

1200 mg MgSO4, 400 mg PSA, 400 mg C18

GCeMS

71e104

0.1e2 mg/Lb

10 mL of water was added initially. Commercial QuEChERS kits

[132]

33 PAHs

Salmon (1 g)

2 mL acetone: EtOAc: isooctane 2/2/1 (v/v/v)

Method 1: 6 g MgSO4, 1.5 g NaOAc Method 2: 4 g MgSO4, 1 g NaOAc, 1 g triNa, 0.5 g di-Na

150 mg MgSO4, 50 mg PSA, 50 mg C18

GCeMS

70e120a

2e10 mg/kg

2 deuterated ISs. Commercial QuEChERS kits. Comparison with EN and AOAC methods

[133]

16 PAHs

Shrimp (10 g)

10 mL ACN

6 g MgSO4, 1.5 g NaCl

150 mg MgSO4, 50 mg PSA

UFLCeMS/ MS

70e120a

20e510 mg/kg

Commercial QuEChERS kits

[134]

16 PAHs

Fish (5 g)

8 mL ACN

6 g MgSO4, 1.5 g NaOAc

900 mg MgSO4, 300 mg PSA, 150 C18

HPLCeFD

70e120a

0.09e1.40 mg/L

Commercial QuEChERS kits

[135]

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.

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Analytes

Sample (Amount)

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35

consisting of the same LLE step but using diatomaceous earth as d-SPE sorbent, 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]. However, 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 diatomaceous 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

ARTICLE IN PRESS 36 Comprehensive Analytical Chemistry

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) acenaphthylene; (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 spectrometry, Anal. Methods 8 (2016) 1711e1720 with permission of Royal Society of Chemistry.

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of this section, it should be pointed out again the work of Knobel and coworkers [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 extracts). 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 products [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 Analytes

Solvents

Salts

Blood (5 mL)

5 mL ACN

2 g MgSO4, 0.5 g NaCl

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

LODs

Comments

References

375 mg MgSO4, 62.5 mg PSA

HPLCeMS/ MS, GCeMS

70 for 47 compounds

1e128 mg/L

A stainless-steel ball was added to break clots formed after addition of ACN. QuEChERS, LLE (similar to first QuEChERS step), QuEChERS using other salt combination (2 g MgSO4 þ 0.5 g NaCl þ 5 g triNa þ 0.25 g di-Na or 2 g MgSO4 þ 0.5 g NaCl þ 0.5 g NaCOOH þ 340 mg HCOOH) were compared. Better results (in terms of efficiency and cleaner extracts) were obtained with the selected QuEChERS method

[140]

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64 Multiresidue compounds (10 cosmetic ingredients potentially allergenic, 5 aromatic amines, 10 flame retardants, 5 industrial chemical additives, 4 pesticides, 3 PAHs, 3 PCBs, 8 PFCs, 1 phenol, 2 plasticisers, 4 preservatives, 3 QACs, 2 SVHCs, 4 UV filters)

Extraction

Sample (Amount)

Soy isoflavones nutraceutical products: capsules, tablets and powder presentation (2 g)

10 mL ACN 1% acetic acid (v/v)

1 g MgSO4, 0.5 g NaOAc

200 mg MgSO4, 100 mg C18

UHPLCeMS/ MS

70e120 for 70 of compounds

0.5e5 mg/kg

8 mL of water was added initially. PSA, GCB, C18, Z-Sepþ and a mixture of them were tested as 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)]. Better results were obtained with LLE extraction plus Florisil cartridges

[24]

3 Synthetic cannabinoids

Urine (0.10 mL), blood (0.10 mL), brain, heart muscle, lung, liver, spleen, kidney, pancreas, adipose tissue (1 g)

Liquid samples: 1 mL ACN solid samples: 9 mL ACN

e

150 mg MgSO4, 25 mg PSA, 25 mg C18

UHPLCeMS/ MS

85e109

0.1 mg/L

QuEChERS extracts were passed through a lipid capturer cartridge

[156]

6 PBDEs

Sediment (1 g)

5 mL hexane:DCM 1/1 (v/v) (three times)

e

1.5 g MgSO4, 300 mg PSA, 50 mg C18

GCeMS/MS

86e113

0.03e0.05 mg/kg

Extraction step was ultrasonically assisted. C18, PSA and GCB were tested as sorbents. QuEChERS and PLE were compared. PLE provided slightly lower LODs

[144]

Continued

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257 Multiresidue compounds (pesticides and mycotoxins)

TABLE 5 Some Examples of the Application of the QuEChERS Method to the Analysis of Miscellaneous Compoundsdcont’d Analytes

Sample (Amount)

Extraction Solvents

Salts

Sorbents in the d-SPE Step

Analytical Method

Recovery (%)

LODs

Comments

References

Sediment (2.5 g)

10 mL ACN: isopropanol 90/10 (v/v)

6 g MgSO4, 1.5 g NaOAc

900 mg MgSO4, 150 mg PSA

LCeMS/MS

63e123

0.03e 0.2 mg/kg

7.5 mL of water was added initially. Acetate buffer and citrate buffer (1 g NaO citrate, 4 g MgSO4, 1 g NaCl, 0.5 g di-Na) were compared. Acetate buffer provided better results. PSA, C18 and GCB were tested as sorbents

[146]

12 Synthetic musks

Personal care products: body and hair wash, toilet soaps, shaving products, dentifrice, deodorants/ antiperspirants, moisturizers and perfumes (500 mg)

3 mL ACN

2.4 g MgSO4, 750 mg NaOAc

180 mg MgSO4, 60 mg PSA, 30 mg C18

GCeMS

50e112

0.01e 5.00 mg/kg

Extraction step was ultrasonically assisted

[141]

13 Paralytic shellfish poisoning toxins

Mussel (1 g)

1 mL 0.1% formic acid (v/v) (two times)

e

10 mg ABS Elut-NEXUS sorbent (polymeric sorbent with nonpolar retention mechanism)

HPLCeMS/ MS

83e113

3e708 mg/kg

Proteins were eliminated before dSPE by adding MeOH and freezing at 20 C

[148]

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6 Steroid hormones

5 Nitrosamines

Cooked bacon (5 g)

10 mL ACN:H2O 1/1 (v/v)

4g ammonium formiate

300 mg MgSO4, 100 mg PSA, 100 mg C18, 100 mg Z-Sep

GCeMS/MS

70e120

0.1 mg/kg

Fats were removed by adding 2 mL of hexane saturated with ACN in d-SPE step

[150]

2 Perfluorinated compounds

Honey (5g)

10 mL ACN 0.15% formic acid (v/v)

4 g MgSO4, 1 g NaCl

900 mg MgSO4, 150 mg styrenedivinylbenzene

UHPLCeMS/ MS

82e86

0.016e 0.040 mg/ kg

5 mL of water was added initially. PSA, SAX, aminopropyl, C18 and Florisil were also tested as sorbents

[143]

6 Polyphenols

Human blood cells (2 mL)

5 mL ACN 1% acetic acid (v/v)

4 g MgSO4, 4 g NaCl

600 mg MgSO4, 100 mg PSA

HPLCeMS/ MS

1e64

0.12e 48.40 mg/ La

Samples were buffered and conjugated analytes were hydrolysed before extraction. Eighteen different methods made by combination of protein precipitation, LLE and SPE were also tested

[153]

2 Betalains

Red beetroot (2 g)

10 mL MeOH:H2O 90/10 (v/v)

4 g MgSO4, 1 g NaCl, 0.01 g diNa, 1 g triNa

900 mg MgSO4, 150 mg SAX

HPLCeMS

e

1.063e 1.166 mg/ kg

PSA, C18, aminoporpyl, Florisil, silica gel and styrenedivinylbenzene were also used as sorbents

[60]

9 Siloxanes

Pine needles, soils (2.5 g)

10 mL DCM:hexane 1/1 (v/v)

6 g MgSO4, 1.5 g NaOAc

900 mg MgSO4, 300 mg PSA 150 mg C18

GCeMS

56e63

1.845e 19.853 ng/ kg

e

[35]

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.

ARTICLE IN PRESS 42 Comprehensive Analytical Chemistry

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. However, 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-3methylimidazolium 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), microwaveassisted 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 consumption 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 oriented 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 determination 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 sorbents 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 technique 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, identifying 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 laboratories 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. Pe´rez, 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 Advances and Developments in the QuEChERS Method Chapter j [5]

[6] [7]

[8] [9]

[10] [11]

[12] [13]

[14]

[15] [16] [17]

[18]

[19]

[20]

45

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. 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.
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. M.L. Schmidt, N.H. Snow, Making the case for QuEChERS-gas chromatography of drugs, TrAC-Trend. Anal. Chem. 75 (2016) 49e56. ´ . Gonza´lez-Curbelo, B. Socas-Rodrı´guez, A.V. Herrera-Herrera, J. Gonza´lez-Sa´lamo, M.A ´ . Rodrı´guez-Delgado, Evolution and applications of the J. Herna´ndez-Borges, M.A QuEChERS method, TrAC-Trend. Anal. Chem. 71 (2015) 169e185. T. Rejczak, T. Tuzimski, A review of recent developments and trends in the QuEChERS sample preparation approach, Open Chem. 13 (2015) 980e1010. 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. S.J. Lehotay, QuEChERS sample preparation approach for mass spectrometric analysis of pesticide residues in foods, Methods Mol. Biol. 747 (2011) 65e91. G. Martı´nez-Domı´nguez, P. Plaza-Bolan˜os, R. Romero-Gonza´lez, 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. 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. AOAC Official Method 2007.01, Pesticide residues in foods by acetonitrile extraction and partitioning with magnesium sulfate, AOAC Int., Gaithersburg, USA, 2007. 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. 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. W. Specht, S. Pelz, W. Gilsbach, Gas-chromatographic determination of pesticide residues after clean-up by gel-permeation chromatography and mini-silica gel-column chromatography, Fresenius J. Anal. Chem. 353 (1995) 183e190. 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 spectrometry, J. Agric. Food Chem. 49 (2001) 4589e4596. 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 46 Comprehensive Analytical Chemistry [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. Gonza´lez, S. Contreras-Lynch, Uptake and depletion curve of diflubenzuron in marine mussels (Mytilus chilensis) under controlled conditions, Aquaculture 460 (2016) 69e74. [24] G. Martı´nez-Domı´nguez, R. Romero-Gonza´lez, F.J. Arrebola, A. Garrido-Frenich, Multiclass 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. ´ . Gonza´lez-Curbelo, S.J. Lehotay, J. Herna´ndez-Borges, M.A ´ . Rodrı´guez-Delgado, [25] M.A 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 environmental pollutants in shrimp, Anal. Chim. Acta 827 (2014) 40e46. [27] M. Anastassiades, Crl-srm 1st Joint CRL Workshop, 2006. Stuttgart, http://www.eurlpesticides.eu/library/docs/srm/1stws2006_lecture_anastassiades_quechers.pdf. [28] H. Chen, J. Marı´n-Sa´ez, R. Romero-Gonza´lez, A. Garrido Frenich, Simultaneous determination 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 Advances and Developments in the QuEChERS Method Chapter j

47

[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, Solventsaving 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. Man˜es, 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. Caˆmara, 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. Ru´bies, 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. Rouille´, 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-Pe´rez, N. Arroyo-Manzanares, L. Havlı´kova´, L. Ga´miz-Gracia, P. Solich, A.M. Garcı´a-Campan˜a, Method optimization and validation for the determination of eight sulfonamides in chicken muscle and eggs by modified QuEChERS and liquid chromatography 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 polymeric 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 ZrO2based 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 48 Comprehensive Analytical Chemistry [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 herbicides 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. Correˆa Pereira, G. Silva, M.B. de Abreu Glo´ria, 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, Evaluation 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 chromatography-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 procedure for the determination of polycyclic aromatic hydrocarbons in soil by gas chromatography-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 analyses 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 solidphase extraction column cleanup, J. AOAC Int. 91 (2008) 422e438.

ARTICLE IN PRESS Advances and Developments in the QuEChERS Method Chapter j

49

[63] R.E. Hunter Jr., A.M. Riederer, P.B. Ryan, Method for the determination of organophosphorus 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. Ucle´s, S. Ucle´s, M. Mezcua, A.R. Ferna´ndez-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 magnesium 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-Mourkidou, Determination of mycotoxins in pomegranate fruits and juices using a QuEChERSbased method, Food Chem. 182 (2015) 81e88. [68] P. Parrilla-Va´zquez, A. Lozano, S. Ucle´s, M.M. Go´mez-Ramos, A.R. Ferna´ndez-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 combined 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.eurlpesticides-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 Fa´tima Facco, T. Medianeira Rizzetti, O.D. Prestes, M.B. Adaime, R. Zanella, C.B.G. Bottoli, Determination of pesticides 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 50 Comprehensive Analytical Chemistry [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-Gonza´lez, F.P.T. Manfo, L. Ga´miz-Gracia, A.M. Garcı´a-Campan˜a, 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 liquidliquid 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. ´ . Gonza´lez-Curbelo, M. Asensio-Ramos, A.V. Herrera-Herrera, J. Herna´ndez-Borges, [87] M.A 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 Advances and Developments in the QuEChERS Method Chapter j

[92]

[93]

[94]

[95]

[96]

[97]

[98]

[99]

[100]

[101]

[102]

[103]

[104]

51

microextraction and stacking before micellar electrokinetic chromatography, Anal. Methods 7 (2015) 5801e5807. Y. Sapozhnikova, Evaluation of low-pressure gas chromatographytandem mass spectrometry method for the analysis of 140 pesticides in fish, J. Agric. Food Chem. 62 (2014) 3684e3689. 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 diversified food types, J. Chromatogr. A 1217 (2010) 4815e4824. 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. 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. S.J. Lehotay, K. Ma
stovska´, 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. A. Hiba, A. Carine, A.R. Haifa, L. Ryszard, J. Farouk, Monitoring of twenty-two sulfonamides in edible tissues: investigation of new metabolites and their potential toxicity, Food Chem. 192 (2016) 212e227. 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. 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. 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 performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, Food Control 60 (2016) 667e676. D. Pimentel-Trapero, A. Sonseca-Yepes, S. Moreira-Romero, M. Herna´ndez-Carrasquilla, Determination of macrocyclic lactones in bovine liver using QuEChERS and HPLC with fluorescence detection, J. Chromatogr. B 1015e1016 (2016) 166e172. 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. 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. M. Lombardo-Agu¨´ı, L. Ga´miz-Gracia, C. Cruces-Blanco, A.M. Garcı´a-Campan˜a, Comparison of different sample treatments for the analysis of quinolones in milk by capillaryliquid chromatography with laser induced fluorescence detection, J. Chromatogr. A 1218 (2011) 4966e4971.

ARTICLE IN PRESS 52 Comprehensive Analytical Chemistry [105] A. Martı´nez-Villalba, E. Moyano, M.T. Galcera´n, Ultra-high performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry for the analysis of benzimidazole compounds in milk samples, J. Chromatogr. A 1313 (2013) 119e131. [106] A. Martı´nez-Villalba, L. Vaclavik, E. Moyano, M.T. Galcera´n, J. Haj
slova, 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. Plo¨ssl, M. Giera, F. Bracher, Multiresidue analytical method using dispersive solidphase extraction and gas chromatography/ion trap mass spectrometry to determine pharmaceuticals 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, zearalenone and its metabolites in eggs using a QuEChERS based extraction procedure, Anal. Methods 7 (2015) 4145e4151. [109] O. Nu´n˜ez, H. Gallart-Ayala, C.P.B. Martins, P. Lucci, New trends in fast liquid chromatography 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 procedures 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. Rodrı´guez-Carrasco, G. Font, J.C. Molto´, 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. Rodrı´guez-Carrasco, J.C. Molto´, H. Berrada, J. Man˜es, 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. Haj
slova, 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. Garcı´a, M. Gaggiotti, J.C. Bası´lico, H.R. Beldome´nico, Multiclass compatible sample preparation for UHPLC-MS/MS determination of aflatoxin M1 in raw milk, Chromatographia 79 (2016) 1091e1100. [116] Y. Rodrı´guez-Carrasco, M. Fattore, S. Albrizio, H. Berrada, J. Man˜es, 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 destruxins 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. Mastovska´, D. Hengst, J. Haj
slova, Mycotoxins in plant-based dietary supplements: hidden health risk for consumers, J. Agric. Food Chem. 63 (2015) 6633e6643.

ARTICLE IN PRESS Advances and Developments in the QuEChERS Method Chapter j

53

[120] E.J. Llorent-Martı´nez, P. Ortega-Barrales, M.L. Ferna´ndez-de Co´rdova, 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 forward using QuEChERS (quick, easy, cheap, effective, rugged, and safe) based extraction and gas chromatography-tandem mass spectrometry-levels of priority polycyclic aromatic 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 metabolites 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-atmospheric pressure photoionization-mass spectrometry for high-sensitivity analysis of US Environmental Protection Agency sixteen priority pollutant polynuclear aromatic hydrocarbons 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 chromatography 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 polycyclic 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 54 Comprehensive Analytical Chemistry [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. Paı´ga, 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-Zamarren˜o, L. Pe´rez-Martı´n, R. Carabias-Martı´nez, QuEChERS method for the extraction of isoflavones from soy-based foods before determination by capillary electrophoresis-electrospray ionization-mass spectrometry, Microchem. J. 108 (2013) 203e209. ´ lvarez, E. Rodrı´guez-Gonzalo, J. Herna´ndez-Me´ndez, R. Carabias-Martı´nez, [137] J. Domı´nguez-A 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 environmental 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, Chemosphere 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 polychlorinated 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 Advances and Developments in the QuEChERS Method Chapter j

55

[149] A. Ru´bies, E. Mun˜oz, D. Gibert, N. Corte´s-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 spectrometry 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-Garcı´a, C.L. Silva, E. Go´mez-Plaza, J.S. Caˆmara, 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 transresveratrol in grapes, Food Anal. Method. 9 (2016) 670e679. [153] M. Mu¨lek, P. Ho¨gger, 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-Olive´, 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-2methoxypyrazines 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 56 Comprehensive Analytical Chemistry

[164]

[165]

[166]

[167]

[168]

[169] [170] [171] [172]

determination of trace amount of bisphenol A in canned foods, Food Anal. Method (2016). http://dx.doi.org/10.1007/s12161-016-0635-y. H. Gallart-Ayala, O. Nu´n˜ez, E. Moyano, M.T. Galcera´n, 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. 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. P. Kaewsuya, W.E. Brewer, J. Wong, S.L. Morgan, Automated QuEChERS tips for analysis of pesticide residues in fruits and vegetables by GC-MS, J. Agric. Food Chem. 61 (2013) 2299e2314. 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. S. Ferhi, M. Bourdat-Deschamps, J.-J. Daudin, S. Houot, S. Ne´lieu, Factors influencing the extraction of pharmaceuticals from sewage sludge and soil: an experimental design approach, Anal. Bioanal. Chem. 408 (2016) 6153e6168. Teledyne Tekman. http://www.teledynetekmar.com/products/semi-volatile-organiccompounds-(svoc)/automate-q40. 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. 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. T. Trent, Determination of carbendazim in orange juice using an automated QuEChERS solution, LC GC N. Am. 26 (September 1, 2014).