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Extraction techniques with deep eutectic solvents
Accepted Manuscript Extraction techniques with deep eutectic solvents Sara C. Cunha, José Fernandes PII:
S0165-9936(18)30118-3
DOI:
10.1016/j.trac.2018.05.001
Reference:
TRAC 15145
To appear in:
Trends in Analytical Chemistry
Received Date: 12 March 2018 Revised Date:
1 May 2018
Accepted Date: 1 May 2018
Please cite this article as: S.C. Cunha, J. Fernandes, Extraction techniques with deep eutectic solvents, Trends in Analytical Chemistry (2018), doi: 10.1016/j.trac.2018.05.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Extraction techniques with deep eutectic solvents
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Sara C. Cunha* and José Fernandes*
3 *Corresponding author:
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José O. Fernandes and Sara C. Cunha: Tel: +351-220428639; Fax: +351-226093390; E-mail: [email protected], [email protected].
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LAQV-REQUIMTE, Laboratório de Bromatologia e Hidrologia, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
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ABSTRACT In last years, a plethora of extraction techniques has emerged as environmental-
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friendly alternatives to conventional extraction procedures. In this particular field, a
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novel class of solvents known as deep eutectic solvents (DES) has arisen as a new
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and very promising tool. Compared with conventional organic solvents, DES as well as
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the so-called natural deep eutectic solvents (NADES) have attracted considerable
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attention due to the fact that they not only are eco-friendly, non-toxic, and
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biodegradable organic compounds but also have a low cost, being easy to produce in
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the own laboratory. The present review provides a critical and organized overview of
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novel extraction techniques using DES as extracting solvents that were applied in food,
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biological and environmental sample analysis. An evaluation of how these
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DES/NADES could improve extraction yields of a variety of analytes and advantages
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and limitations of each proposal will be discussed and compared with earlier studies.
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Keywords: Sample Preparation, Deep Eutectic Solvents, Natural Deep Eutectic Solvents, extraction, Chemical Analysis
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ACCEPTED MANUSCRIPT Abbreviations: AALLME, air-assisted liquid-liquid microextraction, AA-DLME, air-
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assisted dispersive liquid-liquid microextraction, AAS, flame atomic absorption
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spectrometry AAS, CPEs, carbon paste electrodes, DA, daidzein, DAGL, daidzin,
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DEHP, di(2-ethylhexyl)phthalate, DLLME, dispersive liquid-liquid microextraction, DNA,
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Deoxyribonucleic acid, ELISA, Enzyme-Linked Immunosorbent Assay, FAAS, flame
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atomic absorption spectrometry, FT-IR, fourier-transform infrared spectroscopy, GA-
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DLLME, gas air-dispersive liqui-lquid microextraction, GC-ECD, gas chromatography-
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electron capture detector, GC-FID, gas chromatography- flame ionization detector, GT,
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genistein, GTGL, genistin, HBA, hydrogen-bond acceptor, HBD, hydrogen-bond donor,
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HPLC-DAD, high performance liquid chromatography- diode array detection, HPLC-
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UV, high performance liquid chromatography-ultraviolet, HS-SME, headpsace solid-
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single microextraction, HF-LPME, hollow fiber-liquid phase microextraction IAA, Indole-
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3-acetic acid, IBA, 3-indolebutyric acid, 4-IPOAA, 4-iodophenoxyacetic acid, LGH,
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lactic acid–glucose, LIT, lithospermic acid, LPME, liquid phase microextraction, MAE,
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microwave-assisted extraction, MAME microwave microextraction, MDES, magnetic
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deep eutectic solvents, MIPs, Molecularly imprinted polymers, MMWCNT, magnetic
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multi-walled carbon nanotube nanocomposite, NIPs, non-imprinted polymers, NMR,
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nuclear magnetic resonance, OCPs, organochlorine pesticides Ox, oxalic acid,
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PAHs, polycyclic aromatic hydrocarbons, PDA, photodiode array, PCH, 1,2-
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propanediol–choline chloride, PT-SPE, pipette-tip solid-phase extraction, ROS,
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rosmarinic acid, RSD, relative standard deviation,
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salvionalic
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microextraction, S-SIL-MSPD silica-supported ionic liquid-based matrix solid phase
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dispersion, SPE, solid-phase extractions, UAE, ultrasound-assisted extraction,
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UHPLC-UV, ultra-high performance liquid chromatography with ultraviolet detection,
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UAME, ultrasound assisted microextraction, UALPME ultrasound assisted liquid phase
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microextraction USAEME, ultrasound-assisted emulsification microextraction, UPLC-
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TOF-MS, Ultra Performance Liquid Chromatography-Time-of-flight Mass Spectrometry,
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acid,
SDME,
single
drop
SAA, salvionalic acid A, SAB,
microextraction,
SPME,
solid-phase
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ultraviolet-visible
spectrophotometry,
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tetrahydrofuran, VWD, variable wavelength detector.
TIIA,
tanshinone
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THF,
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ACCEPTED MANUSCRIPT 1. INTRODUCTION
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Sample preparation is a common step in trace analytical methods, involving the
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extraction of an analyte or a class of analytes from its original matrix into a solvent in
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order to allow its further analysis by a sensitive and selective way. Conventional
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sample preparation techniques such as multi-step liquid-liquid extraction, Soxhlet
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extraction and solid-phase extraction, among others, are usually time-consuming, labor
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intensive and involve the use of a large volume of organic solvents, which is expensive
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and generate a considerable amount of waste harmful for human health and the
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environment. To overcome these drawbacks, numerous efforts have been made over
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the last decades, to streamline sample extraction procedures and also to reduce or
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eliminate the use or generation of hazardous substances in agreement with the
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principles of the green chemistry [1]. New techniques miniaturizing solid-phase
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extraction or liquid-liquid extraction have appeared such as SPME and LPME,
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respectively. SPME is a solventless extraction technique very popular in recent years
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that use different fiber materials in various configurations for the extraction of a wide
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range of volatile analytes [2]. LPME comprises a range of slightly different techniques
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characterized by using low amounts of sample matrices and small volumes of organic
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solvents. Often it can employ different types of kinetic energy such as ultrasound
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(UAME) or microwave (MAE) in order to improve extraction efficiency, enrichment
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factor and simultaneously reduce extraction time. Progresses made in the last decade
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(2006-2017) in the field of sample extraction are confirmed by the increasing number of
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published scientific articles on SPME, LPME, UAME and MAE. In the ISI Web of
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knowledge there are references for that period of about 11,133 published scientific
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papers on SPME, 1,351 on LPME, 1,790 on UAME and 2,803 on MAE for
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determination of different organic and inorganic compounds, of which more than 60%
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were published in the last five years. The keywords used for this research were: “solid-
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phase microextraction”, “liquid phase microextraction”, “ultrasound assisted extraction”
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and “microwave-assisted extraction”.
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Until some years ago, solvents used in LPME techniques were always associated with
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a certain degree of toxicity, but the recent development of a remarkable generation of
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new extracting solvents, i.e. DES is changing this scenario. These solvents are
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commonly composed of two non-toxic components, one of them with capacity to be a
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HBA (quaternary ammonium, tetralkylammonium or phosphonium salts) while the other
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(acids, alcohols, amines and carbohydrates) possess HBD properties [3]. Generally,
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DES have much lower melting point than that of any of its individual components,
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which is due to the formation of intramolecular hydrogen bonds [4], and possess some
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ACCEPTED MANUSCRIPT noteworthy chemical properties, such as low vapor pressure, relatively wide liquid-
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range, non-flammability and unreactivity towards water [5]. Moreover, DES are easy to
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be prepared not requiring purification steps, are made from low cost compounds,
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present low or negligible toxicity and are biodegradable and easily recyclable. These
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features make DES preferable over the conventional solvents used in extraction
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procedures.
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Similar properties to DES have the so-called NADES, solvents which are prepared
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using natural components produced by cell metabolism. Based on the hypothesis that
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the existence of NADES in living organisms can explain many biological processes,
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several NADES composed of simple molecules always present in living cells (urea,
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amino acids, sugars and choline) have been synthesised and studied in what respect
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their solvent properties [6].
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Indeed, DES and NADES showed to have excellent potential as extracting solvents in
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several sample preparation procedures such as LPME, UAME and MAE. Literature
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research in ISI Web of knowledge indicates a total of 1,303 references about DES and
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56 regarding NADES, of which 321 and 31, respectively, are related with extraction
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procedures. Since 2011 the number of publications has increased considerably, arising
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462 in 2017, 443 of which related to DES and 19 to NADES (Figure 1). According to
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the Web Science Categories, most of these references are within the scope of
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multidisciplinary chemistry, followed by chemistry physical or chemistry analytical,
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respectively. The reason for the increase number of publications in the analytical field
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can be attributed to the unique features of these new liquids such as high thermal
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stability, low thermal conductivity, low volatility and adjustable miscibility as well as the
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capacity to be combined with advanced separation techniques like HPLC and GC. The
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present review, cover applications reported until the end of 2017 and is mainly focused
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on microextraction techniques using DES/NADES as extracting solvents for food,
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biological and environmental sample analysis. The potential of each modern extraction
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technique will be discussed and compared with earlier studies and an evaluation of
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how these techniques could improve extraction efficiency for a variety of analytes will
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be made.
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2. DEEP EUTECTIC SOLVENTS (DES): A BRIEF OVERVIEW
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In the year of 2001, Abbot and co-workers reported that a mixture of a choline chloride
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and a metal salt (zinc chloride) could form a liquid, at temperatures below 100°C [7].
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Two years later, the same group developed a mixture of ChCl with an hydrogen-bond 6
ACCEPTED MANUSCRIPT donor (urea) [8] designating it as DES. In the subsequent years other DES have been
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reported namely that formed by mixing ChCl with different carboxylic acids (oxalic,
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malonic, and succinic acids) [9]. Another major family of DES that have been widely
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explored are those that combine a carbohydrate (or a reduced derivative as is the case
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with sorbitol and mannitol), an urea derivative (N,N’-dimethylurea), and a chloride salt
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(ammonium chloride)[10]. Generally, the melting point of the DES is lower than the
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melting points of each of its starting components. One of the attractive features of
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these novel solvents is the possibility of having, simply by changing one or both
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components, a huge number of eutectic mixtures with different chemical properties.
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Recently, a new class of DES have been synthetized, based on combinations of
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decanoic acid with various quaternary ammonium salts [11] or DL-menthol with several
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natural acids [12]. This new class of DES showed a high hydrophobic behavior in
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contrast to the previous hydrophilic DES [11]. Many extraction procedures can become
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more effective by using these hydrophobic DES due their capability of extracting
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analytes hydrophobic from aqueous solutions. Additionally, these new solvents have
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the ability to extract both dissociated and undissociated forms of acidic compounds,
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broadening the application of hydrophobic DES for different pH environments [11].
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DES are easily produced by just mixing two or more compounds and heating them to
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around 80 °C [8, 13] or freeze-drying [14], without the subsequent need of any complex
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purification step, thus reaction conditions are accessible for any laboratory. However,
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owing to the extreme hygroscopicity of the HBA (e.g. ChCl, tetrabutylammonium, DL-
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menthol), attracting moisture to preparations, a careful manipulation through using
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vacuum conditions is advised. Although ChCl is the most employed quaternary
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ammonium salt because of its low cost and biodegradability (it is indeed produced in
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large scale and added to the chicken feed as nutrient), many other halides
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(methyltriphenylphosphonium
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acetylcholine chloride, tetramethylammonium chloride among others) are suitable for
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making DES [5].
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One of the main features of DES is their possibility to be used as extracting solvent for
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a wide range of chemical different solutes [3]. Their uses as solvents in extraction
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procedures depends on their physical properties, such as viscosity, density, miscibility
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and polarity. It is convenient to select solvents with low viscosity to facilitate mixing but
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with a large density difference from the matrix in order to easy the separation of phases
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[15]. The main physical properties of DES including freezing point, density, viscosity,
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conductivity, and polarity are briefly discussed below in this section and some DES are
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highlighted in Table 1. More detailed information on the properties of DES can be
bromide,
benzyltriphenylphosphonium
chloride,
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references cited therein.
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The DES freezing point is dependent on DES components (type of HBD and HBA) and
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its molar ratio. For instance, the freezing point of a choline salt-derived DES combined
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with urea decreases in the order F- > NO3- > Cl- > BF4- indicating a correlation with the
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hydrogen bond strength [3, 17]. The organic salt/HBD molar ratio has also significant
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effect on the freezing point of a DES. For instance, when ChCl was mixed with urea in
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a molar ratio of 1:1 and 1:2, the resulting DES showed a freezing point >50 °C and 12
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°C, respectively [3].
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DES exhibit in general higher density values than water with levels ranging from 1.041
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g cm-3 to 1.63 g cm-3 [3]. This feature helps the rapid settling of DES phase in phase
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separation devices used in DLLME techniques.
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Most of the DES exhibit a relatively high viscosity at room temperature (> 100 cP) [3].
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This can be of substantial benefit when carrying out SDME, as the high viscosity
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facilitates the suspension of larger drops at the tip of a needle. However, in some
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extraction procedures such as DLLME this characteristic can affect negatively the
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diffusion of analytes. To surpass this drawback some authors, increase the
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temperature during extraction or, alternatively, increase the ChCl concentration, which
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are reported in literature to reduce the viscosity of some eutectic mixtures.
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In general, DES show poor conductivity (lower than 2 mS cm-1 at room temperature) [3]
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due to their high viscosity. However, conductivities of DES increase significantly as the
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temperature increases due to a decrease of the respective viscosity [3, 17, 18].
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Furthermore, the successive addition of ChCl to glycerol lowers the viscosity and
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increases the conductivity (from 0.74 mS cm-1 for a molar ratio of 1-4 ChCl˗glycerol to
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1.30 mS cm-1 for a molar ratio of 1-2 ChCl˗glycerol) [18] due to more available charge
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carriers in an increasingly less viscous solvent.
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Polarity is one of the most important distinguishing characteristics of DES, in view of
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their extraction ability and their miscibility with other solvents. Nevertheless, few studies
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related to DES polarity are published. Abbott and co-workers reported that the polarity
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scale of ChCl-glycerol was similar to RNH3+X-, R2NH2+X-, and imidazolium ionic liquids
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[17, 18]. In DES composed of an ammonium salt and carboxylic acids the acidity is
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mainly provided by the organic acid present in the mixture, and an increase of the alkyl
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side chain of both compounds leads to a lower ability of the solvent to donate protons
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[19]. Carbohydrate derivative DES present higher polariry than those observed for
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short chain alcohols (e.g. ethanol, 2-propanol) and some polar aprotic solvents (e.g.
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dimethylsulfoxide and dimethylformamide) [10].
200 3. NATURAL DEEP EUTECTIC SOLVENTS: A BRIEF OVERVIEW
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Recently, Choi and collaborators have explored natural products as a source of DES
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solvents, including primary metabolites common in living cells (sugars, sugar alcohols,
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organic acids, amino acids, amines) as well as water [6]. NADES can be obtained by
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heating a mixture of two or three components in certain molar ratios in the presence of
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water, which decrease their viscosity and allows the occurrence of extensive inter
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molecular interactions e.g. H-bonds or ionic bonds [20](Table 2). The usually
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components of NADES as HBA are amines (ChCl, ammonium chloride) or amino acids
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(alanine, proline, glycine, betain) while as HBD the more common are organic acids
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(oxalic acid, lactic acid, malic acid, etc.) or carbohydrates (glucose, fructose, maltose,
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etc.).
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As a whole NADES possess excellent properties as solvents [20], e.g., negligible
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volatility, a very low melting point (they are liquid even below -20 oC), a broad polarity
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range and high solubilization power of a wide range of compounds, especially poorly
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water-soluble compounds [6, 20]. The high solubility of scarce water-soluble
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metabolites and macromolecules (e.g. DNA, proteins, cellulose, and amino acids) has
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been demonstrated [20-22] as well as their suitability as media for enzymatic reactions
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[6, 23] and biotransformations [24]. It was verified that NADES composed by 1 mol of
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ChCl and 2 mol of 1,2-ethanediol, glycerol, malonic acid, or urea, the two first present a
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more dipolar nature than the last ones, which can be attributed to the presence of
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alcohol functionalities on 1,2-ethanediol and glycerol [25]. Despite this data, detailed
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information about chemical and physical properties is still scarce, and only few
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applications involving NADES in the analytical field, e.g. extraction of organic
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compounds, are reported. Therefore, a deep research on the preparation of NADES for
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specific applications is still required.
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4. LIQUID-PHASE MICROEXTRACTION
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LPME extraction procedures correspond to efficient alternatives to traditional liquid-
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liquid extraction, offering numerous advantages such as a high degree of concentration
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minute amounts of samples.
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In LPME techniques, usually few microliters of the extracting solvent (usually
233
designated as acceptor phase) are placed directly into the aqueous sample containing
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analytes (donor phase) or in its headspace and later the extracting solvent is collected.
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In the last few years numerous LPME procedures have been developed such as
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SDME, HF-LPME and DLLME. In SDME a drop of extractive solvent is suspended in
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the tip of a syringe which can be immersed in the aqueous phase of the sample or
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exposed to the respective headspace (HS-SME). In HF-LPME the extracting phase is
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placed inside the lumen of a porous polypropylene hollow fiber, to improve the stability
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and reliability of extraction [26]. In DLLME a cloudy solution of small droplets of
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extracting solvent (microliters of a water-immiscible high density organic solvent) is
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formed and dispersed throughout the aqueous phase using a dispersive solvent,
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miscible in both extracting and aqueous phases. Currently some DLLME procedures
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do not require the use of dispersive solvent being in those cases the cloud solution
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obtained either by the injection of air bubbles (GA-DLLME), formation of air bubbles
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using a vortex, or by the mechanic action of sucking and injecting the aqueous solution
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with a syringe (AALLME and AA-DLME). Overall, in all these procedures, extraction
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efficiency is dependent of many factors such as partition coefficient, type and volume of
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extracting and dispersive solvents, sample volume, analyte properties, agitation, ionic
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strength, extraction time, temperature, etc. A detailed discussion of the importance of
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each parameter can be found in the literature [27].
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LPME techniques using DES or NADES as extracting solvent had been used for
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extraction of several polar nonvolatile and volatile compounds from food and water
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matrices (Table 3).
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Tang et al. [28] optimized a two phase HS-SME technique where a DES (ChCl and
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ethylene glycol, 1:4 molar ratio) drop suspended in a tip of a microsyringe needle was
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exposed for 30 min to the headspace of leaf samples to extract bioactive terpenoids.
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The use of a 2 µl DES drop was enough to allow the adsorption of the target
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compounds volatilized from the samples heated at 100 °C and ultrasonicated at 70 W.
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Once stopped the procedure, the suspended drop was retracted back into the
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microsyringe and injected into a GC-FID.
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In the same year 2014, Gu et al. [29] employed a similar HS-SME procedure for the
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extraction of phenolic compounds from crude oils; they also used ChCl and ethylene
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needed and to improve the yields [29].
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A three phase HS-SME procedure using DES (methyltriphenylphosphonium iodide and
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ethylene glycol, 1:4 molar ratio) plus 20% v/w methanol as an acceptor phase and n-
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dodecane as extraction solvent was applied to extract steroidal hormones
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(dydrogesterone and cyproterone acetate) from biological samples (urine and plasma)
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[30]. The analytes were further analyzed by LC-UV, and the obtained performance in
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what respect range of linearity and LOD have compared positively to those reported in
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literature using more sensitive detectors.
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Recently, Yousefi et al.[31] developed a two phase HS-SME procedure using an
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hydrophobic magnetic bucky gel formed by combining DES (ChCl:chlorophenol, 1:2
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molar ratio) and magnetic multiwalled carbon nanotubes for the extraction of volatile
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hydrocarbons from water and urine samples. The extraction was successfully
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completed in 10 min using a drop of 20 µL that was placed in the headspace of the vial
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containing the aqueous sample. The extraction temperature was kept at 30 °C and the
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vial was stirred at 1200 rpm. The use of a large drop compared with other HS-SME
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based DES procedure showed to provide a higher sensitivity. When compared with
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conventional solvents DES showed more adequate to form stable drops for HS-SME
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due to its higher thermal stability, higher viscosity, lower volatility and adjustable
283
miscibility.
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Concerning to DLLME conventional process using DES as extracting solvent it was
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used just by Ferrone et al. [32] for determination of oxyprenylated, phenylpropanoids in
286
vegetable oils. The extraction was performed with 45 µL of DES (phenylacetic acid:
287
betaine, 2:1 molar ratio) and isopropanol (200 µL) as dispersive solvent; following
288
agitation and centrifugation, 5 µL of the bottom phase were injected in a UHPLC-PDA
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system. This method allowed the achievement of good limits of detection, linearity and
290
reproducibility similar or better to those reported in literature for the same analytes.
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A novel rapid and efficient GA-DLLME procedure characterized by the absence of
292
dispersive solvent was developed by Farajzadeh et al. [33] for the extraction of 9
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pesticide residues from fruit and vegetable juices. In the optimized extraction
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procedure, air was bubbled into a test tube to disperse the extracting DES (ChCl: 4-
295
chlorophenol, 1:2 molar ratio) into the aqueous solution, in order to obtain a cloudy
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solution. After centrifugation, an aliquot of the sedimented phase is injected into GC-
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FID for the separation and determination of the enriched pesticide residues [33].
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the cloud solution is obtained by sucking and injecting several times the mixture of
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extracting solvent and aqueous sample. Lamei et al. [34] used this technique
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employing a mixture of ChCl and 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ol
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(1:2 molar ratio) as DES extractor and THF as a demulsifier agent, for the extraction of
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methadone from water and biological samples. Therefore, the dispersion of the
304
aggregated DES droplets into aqueous phase was achieved by the effect of sucking
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and injecting (10 times) the mixture of sample, extracting solvent and demulsifier agent.
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After a brief centrifugation the uplayer was directly analyzed by GC-FID. A pronounced
307
advantage in comparison to the other LPME described in the literature for methadone
308
extraction is the low toxicity and low cost of the extracting solvent used.
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AA-DLLME was developed and optimized by Ge et al. [35] for pre-concentration and
310
separation of 6 benzophenones from different types of waters. Using a hydrophobic
311
DES (mixture of DL-menthol and decanoic acid, 2:1 molar ratio) as extractor solvent,
312
which was several times injected into the aqueous solutions, the authors were able to
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extract efficiently the benzophenones without the use of dispersive solvents.
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In a similar way, Zheng et al. [36] used a hydrophobic DES with 1-decyl-3-
315
methylimidazolium chloride and 1-dodecanol (1:2, molar ratio) for the extraction of
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benzoylureas from waters, followed by HPLC-UV analysis. Various conditions were
317
optimized, namely the type and volume of extractor, salt addition, vortex time,
318
temperature of extraction and pH of the aqueous sample. The authors concluded that
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8.0 mL of sample solution with 450 mg sodium chloride and pH at 4-6 provided the best
320
recoveries when extracted with 40 µL of DES during 3 min in vortex at 40 °C.
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Since the discovery of NADES by the Choi group [6] several works have been
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published by the same research group exploring the potential of NADES as solvents to
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extract bioactive compounds such as antocyanins, and phenols from several solid
324
samples (Table 3) [20, 37, 38]. In general, a low amount of sample (<100 mg) is
325
extracted with a small volume of the chosen NADES (< 3 ml) at controlled temperature
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(40 ºC) using vortex stirring. A pronounced advantage of the use of NADES in LPME in
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comparison to the conventional extracting solvents is the higher stability of the extract
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obtained and, of course, the use of a solvent sustainable and environmental-friendly.
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In 2013, Dai et al. [20] tested different NADES and a multivariate data analysis to
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demonstrate that the extractability of a wide range of phenolic compounds (hydrophilic
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and hydrophobic metabolites of safflower) were greater with NADES than with
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conventional solvents. This high extractability was attributed to H-bonding interactions
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continued the previous work, exploring the ability of different NADES to stabilize
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unstable phenolic compounds extracted from safflower such as carthamin [38]. They
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found that carthamin is more stable in glucose-ChCl and sucrose-ChCl than in acidic
337
NADES such as proline-malic acid or lactic-acid-glucose and the stabilization aptitude
338
of NADES increases with increasing viscosity (low water content). Lately, Dai et al [39]
339
tested diverse NADES for the extraction of anthocyanins from purple and orange petals
340
of Catharanthus roseus. Among the NADES evaluated, LGH and PCH showed to
341
present a similar extraction power for anthocyanins as conventional organic solvents,
342
with the additional advantage exhibited by LGH to provide at least three times higher
343
stability capacity for cyanidins than acidified ethanol, facilitating their extraction and
344
further analysis by UPLC-TOF-MS.
345
These works clearly showed that both DES and NADES have a high potential as
346
extracting solvents for a wide range of analytes of low to medium polarity and
347
demonstrated a bright future for the application of these novel classes of extracting
348
solvents in LPME field.
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349
5. ULTRASOUND ASSISTED MICROEXTRACTION
351
In UAME techniques the extraction procedure takes place under ultrasonic energy
352
(typical systems use a frequency energy of 40 kHz), which favors the contact between
353
sample and extracting solvent. Ultrasounds radiation can be applied by means of
354
water-baths or ultrasonic probes, being the last ones able to deliver higher energy input
355
per volume due to a more focused and uniform power input. Conversely, ultrasonic
356
probes provide an entire control over the most important sonication parameters,
357
leading to more reproducible results [40].
358
In general, extraction efficiency of UAME techniques depends on different factors such
359
as extracting solvent (type, pH, volume), ultrasonic conditions (temperature, amplitude
360
of sonication, sonication time), and sample features (matrix, amount, particle size) [40,
361
41].
362
The main advantage of using UAME compared with conventional DLLME is that no
363
dispersive solvent is needed to achieve a high surface area of contact between the
364
extracting solvent and sample. Additionally, UAME can promote a greater penetration
365
of the extracting solvent in solid samples matrices.
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ACCEPTED MANUSCRIPT DES based UAME have been applied mainly for extraction of organic compounds from
367
liquid samples, although their application to solid samples or to the extraction of
368
inorganic analytes has also been proposed (Table 3). Some works have explored the
369
use of magnetic DES or NADES as extracting solvents with the purpose to simplify the
370
process and improve yields. In general, UAME involves lower volumes of DES (less
371
than 500 µL) and shorter times of extraction (less than 15 min), than the previous
372
mentioned LPME techniques. Like LPME, UAME also did not allow automation of the
373
extraction process.
374
Cvjetko Bubalo et al. [42] used a ChCl-based DES containing oxalic acid as a
375
hydrogen bond donor with 25% of water, for the extraction of grape skin phenolic
376
compounds. To increase extraction yield, samples were sonicated in a water bath
377
during 50 min at 65 °C. According to the authors, t he extraction efficiency obtained by
378
UAME was higher than those obtained with microwave-assisted extraction or
379
conventional extraction methods.
380
Recently, Zhuang et al. [43] combined DES-UAME with HPLC-UV for the simultaneous
381
determination of flavonoid glycosides and respective aglycones in Platycladi Cacumen.
382
In the optimized conditions, 1 ml of DES (ChCl- laevulinic acid with 75% of water) was
383
mixed with 25 mg of sample during 30 min at 50°C un der an ultrasound bath (200 W,
384
40 kHz); the extract was further diluted 8 times with acetonitrile before HPLC-UV
385
analysis. Additionally, the authors evaluated the possibility to recover the target
386
analytes from the DES extracts, in order to enable their further application in
387
pharmaceutical or food industry. For that purpose, several macroporous resins were
388
evaluated, being the best results for both flavonoid glycosides and aglycones obtained
389
with LX-38.
390
Khezeli et al. [44] have reported a simple and highly reproducible UAME method for the
391
determination of ferulic, caffeic and cinnamic acids in olive, almond, sesame, and
392
cinnamon oil samples, using ChCl and ethylene glycol (1:2, molar ratio) as DES
393
extracting solvent. The solvent was added to the sample dissolved in n-hexane, then
394
the mixture was placed in an ultrasound bath for 5 min, to form an emulsion of
395
microdroplets, and consequently increase the contact surface between DES and
396
sample. Once completed the extraction, the DES phase containing the analytes was
397
separated by centrifugation, and submitted to HPLC-UV analysis. The results indicated
398
that the novel approach have shown the advantages of good sensitivity (limits of
399
detection between 0.39 and 0.63 µg/L), reproducibility (RSD <5.1%), convenience
400
(extraction time less than 15 min), and high accuracy (recoveries from 95-105%). Tan
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ACCEPTED MANUSCRIPT 401
et al. [45] employed also UAME-DES followed by HPLC/UV for determination of plant
402
growth
403
tetramethylammonium chloride–ethylene glycol mixture (1:3 molar ratio). When
404
compared with other techniques such as SDME, SPME and S-SIL-based MSPD the
405
UAME-DES proposed in the works above referred are more sensible, fast and simple
406
of execution [39, 40].
407
The applicability of hydrophobic DES for extraction of analytes dissolved in raw waters
408
such as UV-filters have been evaluated by Wang et al [46]. After optimization of diverse
409
parameters (for examples sample volume, salt addition, sample pH, ultrasonic time) the
410
authors proposed the use of a mixture of trioctylmethylammonium chloride with
411
decanoic acid (1:3 molar ratio) as DES, using sonication for 5 min in an ultrasonic bath
412
(150 W; 40 kHz) for pre-concentration and separation of three benzophenones. This
413
method has the great advantage of enabling the extraction and purification in one step
414
without the use of toxic solvents.
415
The use of a magnetic deep eutectic solvent (MDES) formed by the mixture of ChCl
416
with phenol and anhydrous FeCl3 (1:2:1 molar ratio) was recently proposed by Khezeli
417
et al. [47] for the extraction of thiophene from a heptane solution. The MDES was
418
dispersed into the solution by ultrasounds during 5 min, in order to enhance the mass
419
transfer of thiophene from n-heptane to MDES phase. After that, microdroplets of
420
MDES were collected by a magnet and the remained concentration of thiophene in n-
421
heptane was analyzed by GC-FID. The method provided very good results in the
422
elimination of thiophene from the initial solution (close to 100%), with the great
423
advantage of eliminating the centrifugation step usually required in any LPME
424
extraction. According to the authors, the developed MDES are able to be reused after
425
four runs without losses of extraction efficiency.
426
A novel UAME application based on DES, named by the authors as emulsification
427
liquid-liquid microextraction (ELLME-DES) was introduced by the group of Khezeli [48]
428
for the simultaneous extraction of BTE (benzene, toluene, and ethylbenzene) and
429
seven polycyclic aromatic hydrocarbons from water samples. Here, the ultrasound
430
helps both the mass transfer between phases and the formation of tiny emulsified
431
droplets, increasing the contact area. Other novelty was the use of a water miscible
432
aprotic solvent, THF for instance, able to decrease the tendency of water molecules to
433
interact with DES and thus promoting the self-aggregation of DES microdroplets.
434
Briefly, 100 µL of DES (mixture of ChCl:phenol in 1:2, 1:3, and 1:4 molar ratios) were
435
added to 1.5 mL of sample and a homogeneous solution was formed immediately. The
from
several
vegetable
oil
samples,
using
as
DES
a
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regulators
15
ACCEPTED MANUSCRIPT further injection of 100 µL of THF followed by sonication for 20 min in an ultrasonic bath
437
provided a turbid state in which DES microdroplets are entirely disperse along all the
438
water phase, so enhancing the transference rate of the compounds from the water to
439
the DES phase. After a centrifugation step (10 min at 3000 rpm) the DES upper phase
440
was withdrawn through a micro-syringe and analyzed by HPLC/UV. Very good results
441
were obtained in what concerns linearity, precision, and accuracy. These approach
442
could be very useful for the multi-analysis of hydrocarbons in environmental water
443
samples, with the advantages of simplicity, low cost, and high sensitivity providing by
444
the high enrichment factor of the extraction procedure, while avoiding the use of
445
chlorinated solvents.
446
Similar approach was used by Aydin et al. [49] for the extraction of malachite green
447
from farmed and ornamental aquarium fish water samples followed by a simple UV–
448
VIS spectrometry analysis. The developed method presented good extraction
449
recoveries (≥95%) and high precision (RSD < 4% for real samples) for evaluation of
450
this anti-parasite which its illegally used in the aquaculture industry to prevent fish
451
diseases caused by external parasites and fungus. Moreover, the method showed a
452
good selectivity for malachite green along with other advantages such as simplicity, low
453
cost, rapid separation and ease of operation. The same authors proposed a ELLME-
454
DES combined vortex for separation and pre-concentration of curcumin in herbal tea
455
samples followed by UV-Vis determination using 400 µL of DES (ChCl: phenol, molar
456
ratio 1:4) as extracting solvent, 400 µL of THF as emulsifier agent and 2 min of
457
ultrasonication to achieve the best extraction[50].
458
The same principles were at the base of the application of DES as extracting solvent
459
on UAME procedures for extraction of inorganic compounds, namely cobalt (II) and
460
chromium (III/VI) ions from aqueous matrices, performed by the group of Soylak [51]
461
[52]. In both works, the metals were previously complexed by adding as ligands 1-
462
nitroso-2-naphthol and sodium diethyldithiocarbamate, respectively, allowing the
463
formation of very stable and hydrophobic complex and consequently promoting the
464
extraction efficiency. The DES solvents were mixtures of ChCl with phenol (4:1, and
465
3:1 molar ratios, respectively) and THF was added to allow the self-aggregation and full
466
separation of the DES molecules from the water phase. Following sonication for 2 min
467
and centrifugation, the authors were able to recollect a DES aggregate containing the
468
complexed metals, suitable for quantification by AAS. Several parameters affecting the
469
extraction performance of the analytes were optimized, namely sample amount, pH,
470
type and volume of DES, of complexing agent, and of emulsifier solvent, and
471
ultrasonication time. The results obtained under the optimized conditions are
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16
ACCEPTED MANUSCRIPT comparable or even better to those reported in literature for the same analytes, apart
473
from presenting a high enrichment factor and consequently low detection limits.
474
A comparable approach to those previously described was used by Panhwar et al. in
475
two works aiming the pre-concentration of inorganic compounds from water and food
476
samples, namely hydrophobic chelates of Se(IV) with 3,3′-diaminobenzidine [53] and Al
477
(III) with 8-hydroxyquinoline [54] before ETAAS analysis. In both works mixtures of
478
ChCl:phenol were used as extractors with a molar ratio of 1:3 and 1:4, respectively,
479
and THF was the emulsifier agent. The authors compared the proposed methods with
480
other ETAAS procedures previously used, in which the pre-concentration was done
481
with LLE, SPE or conventional DLLME, and found no significant differences between
482
the performance data achieved, with the advantages already indicated that
483
characterize the use of DES.
484
The use of NADES in UAME is been increasing in last years as mentioned for other
485
microextraction techniques. Lores et al. [55] used a fructose-citric acid NADES mixture
486
in combination with UAE for fast and green gluten determination by ELISA. The
487
NADES-UAME developed allows the replacement of the ethanol-water solution
488
commonly used for gluten extraction with success, once good recoveries (62–135%)
489
and high precision RSD < 15%) were obtained. In another work, Bajkacz and Adamek
490
[56] used NADES combined with UAME for the isolation of isoflavones (daidzin,
491
genistin, genistein, daidzein) from soy products followed by UPLC-UV analysis. The
492
best results were obtained using a mixture of ChCl:citric acid (1:1 molar ratio) with a
493
water content of 30%, and a ratio of NADES volume to sample amount of 3 The
494
extraction time was 60 min at 60ºC and the ultrasonic power was 616 W. Bosiljkov et
495
al. [57] used chemometric tools, namely a response surface methodology to optimize
496
NADES-UAME/HPLC-DAD method for the quantification of anthocyanins in wine lees.
497
The maximum amount of extracted compounds were achieved using ChCl:malic acid
498
(1:1 molar ratio) with 35.4% (w/w) of water in a ultrasound bath at 341.5 W during 30.6
499
min. Recently, Huang et al [58] used a NADES-UAME/HPLC-UV method for the
500
extraction of rutin from from tartary buckwheat hull. The authors proved that the
501
solubility of rutin increased by 660–1577 times in ChCL-glycerol-based NADES when
502
compared to water.
503
The increasing number of works using DES and NADES in UAME, in recent years
504
make us believe that this novel class of extracting solvents can be used in removal and
505
extraction of a wide range of analyte in environmental and food matrices. Despite all
506
the advantages, the majority of the DES extracting solvents used in UAME described
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ACCEPTED MANUSCRIPT 507
procedures requires the use of HPLC for organic compounds, or ETAAS and AAS for
508
inorganic compounds, as quantitative final technique, due to the incompatibility with GC
509
systems due to DES low volatility.
510
6. MICROWAVE-ASSISTED EXTRACTION
512
MAE employs non-ionized electromagnetic irradiation (in a frequency range of 0.3-300
513
GHz) to heat both solvent and samples by movements of ions and rotation of molecular
514
and atomic dipoles, in order to increase extraction kinetics [59].
515
MAE may be performed in closed vessels under pressure (pressurized MAE) or in
516
open vessels at atmospheric pressure (focused MAE). The first ones are most used in
517
food analysis since usually provide enhanced extraction yields. The extraction
518
efficiency is dependent on the solvent (nature and solvent/sample ratio), temperature
519
and pressure, extraction time, radiation power, sample composition (moisture mainly),
520
and particle size (preferably 0.1 – 2 mm)[41, 59].
521
MAE using DES as extracting solvent was employed by Chen et al. [60] to extract 5
522
active ingredients namely rosmarinic acid, lithospermic acid, salvionalic acid B,
523
salvionalic acid A, and tanshinone II A from Radix Salviae miltiorrhizae followed by
524
HPLC-VWD quantification. Among twenty-five DES tested, the authors concluded that
525
ChCl-1,2-propanediol (1:1, molar ratio) showed the best yields. Other extraction
526
factors, including temperature, time, power of microwave, and solid/liquid ratio, were
527
systematically investigated by response surface methodology. The hydrophilic and
528
hydrophobic compounds were extracted simultaneously under the optimized
529
conditions: 20 vol% of water in ChCl-1,2-propanediol as solvent, microwave power of
530
800 W, temperature at 70°C, time at 11.11 min, and solid/liquid ratio of 0.007 g/ml. The
531
proposed DES combined with the MAE provided a prominent advantage for fast and
532
efficient extraction of active compounds compared with conventional procedures.
533
Moreover, in comparison to the techniques previously used, MAE allows the
534
automation of the extraction (40 samples per batch). The main limitations of MAE
535
based techniques are the higher costs of the equipment and the usual presence on the
536
extracts of many interfering compounds due to the exhaustive extraction process,
537
which requires a cleanup step prior to the analysis.
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538 539
7. OTHER APPLICATIONS OF DES/NADES IN EXTRACTION TECHNIQUES
18
ACCEPTED MANUSCRIPT 540
DES have been also demonstrated to be an interesting alternative as reaction solvents
541
in the production of new sorbents [61] or polymeric phases [62] used in solid-phase
542
extractions (SPE), which enhance the range of possible DES applications in
543
environmentally friendly extraction procedures. Another application is using DES as
544
dissolution solvent [63] as a new alternative to the conventional Soxhlet extraction.
545 7.1. DES as solvents on liquid-liquid extraction
547
Guo et al. [64] used a DES based on tetrahylammonium chloride and phenol (0.8:1,
548
molar ratio) to extract phenol (99.9%) from model oil (toluene). The extraction was
549
achieved by mixing directly the DES with the matrix by 30 min at room temperature,
550
avoiding the use of alkali and acids and the production of phenol containing waste
551
water, common in the traditional methods. The same group previously has verified that
552
the addition of ChCl allowed a formation of DES due to the presence of phenols
553
(phenol, cresols) in model oils (hexane, toluene, and p-xylene) [65]. The extraction of
554
phenolic compounds from virgin olive oil using DES as extracting solvent was
555
evaluated by García et al. [66]. The best results for the two most abundant secoiridoid
556
derivatives (oleacein and oleocanthal) were obtained with ChCl: xylitol (2:1, molar ratio)
557
and chlorine chloride:1,2 propanediol (1:1, molar ratio) as DES solvents. The better
558
conditions were achieved by mixing the extractive solvent directly with the samples
559
inside a bath at 40°C with agitation for 1 h. Excel lent extraction yields were obtained
560
with the tested DES compared with the commonly used mixture of methanol/water.
561
Despite all the advantages due to the use of DES such as low cost and low toxicity, the
562
extraction time was not reduced.
563
The group of Ghanemi [67] for determination of PAHs by HPLC-UV used DES (ChCl–
564
Ox, 1:2 molar ratio) at 55°C for 30 min to dissolve fish samples. After dissolution, PAHs
565
were quantitatively extracted from ChCl-Ox solution with 5 ml of cyclohexane and
566
stirring for 20 min [67]. These procedures provide some operational advantages when
567
compared with the conventional Soxhlet extraction such as simplicity, low-cost and
568
eco-sustainability of the eutectic solvent, relatively high-speed sample preparation and
569
low consumption of both sample and organic solvents. Similar advantages were also
570
described by Bi et al. [68] who applied a mixture of ChCl and 1,4-butanediol (1:5 molar
571
ratio) with 35% of water at 70°C for 40 min for the extraction of antioxidant flavonoids
572
(myricetin and mentoflavone) from leave plants, using a sample/volume ratio of 1 g/10
573
ml.
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574 575
7.2. DES as sorbent on solid-phase extraction 19
ACCEPTED MANUSCRIPT Solid-phase extraction (SPE) is one of the most popular extraction techniques, making
577
use of a wide range of supporting packings commercially available with different
578
sorbents. Depending on the nature of the sorbent, a number of mechanisms of solute
579
retention can be assumed to rule the process. Partitioning of analytes between a liquid
580
solution (sample matrix or extract) and a viscous liquid that is immobilized on a solid
581
support (sorbent phase) is the most usual retention mechanism for SPE process.
582
Liquid/solid adsorption as well as ion exchange or size exclusion are also possible
583
mechanisms in various separations [69]. SPE extraction is a safe, efficient and
584
reproducible separation technique that can be automatized.
585
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576
Wang et al. [61] employed DES (ChCl and urea, 1:2 molar ratio) as reaction solvent to
587
prepare a new nitro-substituted tris(indolyl)methane modified silica phase. This new
588
sorbent was used in the extraction of organic acids (benzoic, p-anisic, salicylic and
589
cinnamic acids) from grape juice and mineralized drinking water followed by HPLC-
590
DAD analysis. Owing the multiple intermolecular forces of the new phase, such as π–
591
π, hydrogen bonding and hydrophobic interactions, good extraction efficiency
592
(recoveries >68%) was achieved for the selected organic acids. Another important
593
advantage of this SPE sorbent is the possibility to be reused, which decrease the cost
594
of the analysis.
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595
Liu et al. [70] used a DES (ChCl: ethylene glycol) to modify graphene. Compared with
597
conventional graphene, DES-graphene had a large winkle and formed a structure with
598
a high specific surface area because linked groups were introduced into the parent
599
graphene structure what give it a higher adsorption ability. Two milligrams of DES-
600
graphene were employed to pipette-tip SPE of sulfamerazine from river waters followed
601
by HPLC analysis. The optimization of PT-SPE included the evaluation of volume of
602
washing and elution solvent. Under the optimum conditions this method showed good
603
recoveries (91-97%) and higher precision intraday (RSD range from 1.6 to 3.5%) and
604
interday (RSD range from 0.7-3.8%).
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7.3. DES as dissolution solvent
607
DES have been used by the group of Ghanemi [63] for the dissolution of marine
608
biological samples, which facilitated the quantitative extraction of some metals under
609
study with small volumes of dilute nitric acid for determination by FAAS. Briefly, in this
610
method, 100 mg of the sample were dissolved in ChCl–Ox (1:2, molar ratio) at 100 °C
611
for 45 min. Then, after addition of 5.0 mL HNO3 (1.0 M) the mixture was centrifuged 20
ACCEPTED MANUSCRIPT 612
and the supernatant analyzed. This procedure provided some clear advantage when
613
compared with other techniques (microwave or ultrasonic acid digestion) such as low-
614
cost and simplicity of the sample preparation while avoiding the formation of highly
615
carcinogenic nitrous vapors.
616 7.4. DES as carbon paste electrode
618
Carbon paste prepared through a mixture of carbon (graphite) powder and a binder
619
(pasting liquid), has been used in the preparation of various electrodes, sensors, and
620
detectors [65]. Currently, CPEs represent a popular type of electrode, because carbon
621
pastes are easily obtainable at minimal costs and can be modified simply to obtain
622
quantitatively new sensors with the desired properties. The basic requirements for a
623
pasting liquid are its practical insolubility in the solution under measurement, a low
624
vapour pressure to ensure both mechanical stability and long lifetime, and further, in
625
the case of voltammetric and amperometric applications, its electrochemical inactivity
626
in the potential window of interest [71].
627
Zhu et al. [62] used a NADES composed of ChCl and urea (2:1 molar ratio) mixed with
628
graphite power to prepare a CPE, which was used to directly extract DEHP from
629
polymer films. The microextraction process follows an exponential association function
630
with the apparent first order rate constant of 6.35×10-4 s-1.
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617
631
7.5. DES as modified molecular imprinted polymers (MIP)
633
MIPs are crosslinked polymers containing specific recognition sites (involved in various
634
types of interactions- covalent, non-covalent and semi-covalent) with a predetermined
635
selectivity for a target analyte. This technique provides several advantages, such as
636
high selectivity and great stability to heating and pH shifts when compared with SPE
637
and LLE. MIPs have been commonly employed in the preconcentration of analytes,
638
acting as the selective adsorbent of SPE [72]. However, MIP’s preparation can pose
639
some problems, like inconsistent molecular recognition, polymer swelling in
640
unfavorable solvents, slow binding kinetics, and potential sample contamination by
641
template bleeding [72].
642
Li et al. [73] compared the efficiency of a DES (synthesized with ChCl and glycerol, 1:2
643
molar ratio) modified molecular imprinted polymer a DES modified non-imprinted
644
polymers (without template), a MIP (without DES) and a NIP (without DES and without
AC C
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21
ACCEPTED MANUSCRIPT template) for the purification of chlorogenic acid from honeysuckles. The extract of
646
honeysuckles was previous obtained using ultrasound (20 min), ethanol at 60% and a
647
ratio of liquid to material (15 ml/g). Among the polymers proposed the DES-MIPs used
648
as SPE showed the highest adsorption capacity owing to its specific imprinted
649
recognition and the DES improved affinity, selectivity and adsorption in purification.
650
A similar approach was applied by the same group more recently using DES formed by
651
ChCl and glycerol (1:2 molar ratio) to synthetize a novel MIP/SPE. The application was
652
successfully applied in the purification of chloromycetin and thiamphenicol from milk
653
[74].
654
8.
655
MICROEXTRACTION TECHNIQUES
656
A broad range of analytical extractive and microextractive techniques have been
657
developed using DES/NADES as extracting solvents for many quantitative analytical
658
purposes such as ETAAS determination of inorganic compounds, and HPLC and GC
659
determination of organic compounds. In the majority of the cases, when DES/NADES
660
are employed as extracting solvent in various DLLME, UAME, MAE and other
661
microextractions procedures, HPLC is preferred to GC as final quantitative technique
662
since the low volatility of the DES/NADES hinder the GC analysis. Nevertheless, Tang
663
et al. [28], Farajzadeh et al. [33], Lamei et al.[34] and Khezeli et al. [47] have
664
successfully employed GC-FID for quantification of several organic compounds using
665
the direct injection of DES extract. The possible contamination of the GC system
666
namely column and injector due to insufficient volatilization of DES extracts was not
667
mentioned in these works. Therefore, the advantages of the use of DES with
668
microextraction techniques, avoiding the toxicity associated with the use of organic
669
solvents, are added to the analytical possibilities of GC. Furthermore, DES as extractor
670
possess an extensive range of polarity/volatility which can be useful in many pre-
671
concentration and separation processes.
TECHNOLOGIES
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673
9. OUTLOOK OF DES/NADES SOLVENTS WITHIN GREEN ANALYTICAL
674
CHEMISTRY
675
According to the twelve principles that govern the concept of Green Chemistry
676
proposed by Anastas and Warner[1], analytical methods should reduce or eliminate
677
hazardous substances used in or generated by a method. The use of DES/ NADES as 22
ACCEPTED MANUSCRIPT extracting solvents in sample preparation techniques fits perfectly with this approach
679
due to their low toxicity and high biodegradability. Additionally, strategies that combine
680
the use of low volumes of these solvents such as LPME, MAE and UAME with green
681
analytical techniques like thermogravimetric, electrochemical or immunoassays
682
analysis [75, 76] are regarded as very interesting green analytical approaches. Despite
683
most of the described sample preparation methodologies presented in the previous
684
sections can be fully considered as environmental-friendly, especially due to low green
685
solvent consumption, the further use of a chromatographic analytical determination
686
commonly associated increases energy costs of the analysis which is somehow a
687
drawback for the analytical method greenness (Table 3). According the existing green
688
analytical evaluation tools (National Environmental Methods Index and Eco-scale) [75,
689
76] the most energy-consuming techniques are NMR, GC-MS, LC-MS, and X-ray
690
diffractometry as opposed to immunoassay, spectroscopy, and electrochemical
691
techniques that are the more energy saved. Additional penalty points on the scales of
692
assessment of analytical methods greenness comes from the requirements of
693
calibration and validation of the methods, since the use of calibration solutions, internal
694
and external standards, standard reference materials or isotope dilution enhance
695
reagents consumption and waste generation [76]. In summary, ideal green analytical
696
methods will be those that eliminate or minimize the use of hazardous solvents, reduce
697
energy use and generate minute quantities of wastes. Therefore, clear efforts are still
698
needed to be made to encourage the development of sustainable analytical methods
699
based on the use of DES and NADES solvents. Information regarding the performance
700
of (micro)extraction techniques based on application of DES/NADES are highlighted in
701
Table 4.
702
10. CONCLUSIONS AND FUTURE PERSPECTIVES
703
In sample preparation, the choice of the right extracting solvent is essential to achieve
704
a near-complete extraction of the analytes of interest, simultaneously with minimizing
705
the amount of interferents. For this purpose, a new class of alternative and
706
environmental-friendly DES and NADES solvents have been employed in several novel
707
microextraction techniques such as LPME, UAME and MAE as well as in more
708
conventional extraction procedures like SPE. Indeed, by replacing conventional
709
solvents with DES the main merits of microextraction techniques such as simplicity of
710
operation, low cost, and environmental safety were enhanced. Additionally, the
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selective and sensitive achieved by the new analytical methods designed for food and
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environmental analysis was often better than those obtained by conventional extraction
713
techniques.
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ACCEPTED MANUSCRIPT There is no doubt that the application of DES and NADES solvents in food and
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environmental analysis will grow in a near future. Forthcoming studies and
716
developments utilizing DES may focus on the following areas; (I) synthesis of new DES
717
and NADES solvents with different polarities and their exploitation in the development
718
of novel extraction techniques for multi-analyte food and environmental analyses; (II)
719
enhancement of the performance and selectivity of the several microextraction
720
techniques to help the execution of the extraction and separation procedure in the
721
analytical laboratories; and (III) employment of new DES and NADES as extracting
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solvents, sorbents or selective binding agents for the trace analysis of contaminants in
723
both food and environmental samples.
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ACCEPTED MANUSCRIPT 725
ACKNOWLEDGMENTS
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Sara C. Cunha and José Fernandes thanks REQUIMTE, FCT (Fundação para a Ciência e a Tecnologia) and FEDER through the project UID/QUI/50006/2013 – POCI/01/0145/FEDER/007265 with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020. Sara C. Cunha acknowledges FCT for the IF/01616/2015 contract.
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731 References
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ionization detection for the determination of some pesticide residues in fruit and vegetable samples, J Sep Sci, DOI 10.1002/jssc.201700052(2017). [34] N. Lamei, M. Ezoddin, K. Abdi, Air assisted emulsification liquid-liquid microextraction based on deep eutectic solvent for preconcentration of methadone in water and biological samples, Talanta, 165 (2017) 176-181. [35] D. Ge, Y. Zhang, Y. Dai, S. Yang, Air-assisted dispersive liquid-liquid microextraction based on a new hydrophobic deep eutectic solvent for the preconcentration of benzophenone-type UV filters from aqueous samples, J Sep Sci, DOI 10.1002/jssc.201701282(2017). [36] H. Zeng, K. Qiao, X. Li, M. Yang, S. Zhang, R. Lu, J. Li, H. Gao, W. Zhou, Dispersive liquidliquid microextraction based on the solidification of deep eutectic solvent for the determination of benzoylureas in environmental water samples, J Sep Sci, 40 (2017) 45634570. [37] Y. Dai, J. van Spronsen, G.J. Witkamp, R. Verpoorte, Y.H. Choi, Ionic liquids and deep eutectic solvents in natural products research: mixtures of solids as extraction solvents, J Nat Prod, 76 (2013) 2162-2173. [38] Y. Dai, R. Verpoorte, Y.H. Choi, Natural deep eutectic solvents providing enhanced stability of natural colorants from safflower (Carthamus tinctorius), Food Chem, 159 (2014) 116-121. [39] Y. Dai, E. Rozema, R. Verpoorte, Y.H. Choi, Application of natural deep eutectic solvents to the extraction of anthocyanins from Catharanthus roseus with high extractability and stability replacing conventional organic solvents, J Chromatogr A, 1434 (2016) 50-56. [40] H.M. Santos, Lodeiro, C. and Capelo-Martínez, J.-L. , The Power of Ultrasound, in Ultrasound in Chemistry: Analytical Application, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany2008. [41] R. Cruz, S.C. Cunha, A. Marques, S. Casal, Polybrominated diphenyl ethers and metabolites – An analytical review on seafood occurrence, TrAC Trends in Analytical Chemistry, 87 (2017) 129-144. [42] M. Cvjetko Bubalo, N. Curko, M. Tomasevic, K. Kovacevic Ganic, I. Radojcic Redovnikovic, Green extraction of grape skin phenolics by using deep eutectic solvents, Food Chem, 200 (2016) 159-166. [43] B. Zhuang, L.-L. Dou, P. Li, E.H. Liu, Deep eutectic solvents as green media for extraction of flavonoid glycosides and aglycones from Platycladi Cacumen, Journal of Pharmaceutical and Biomedical Analysis, 134 (2017) 214-219. [44] T. Khezeli, A. Daneshfar, R. Sahraei, A green ultrasonic-assisted liquid-liquid microextraction based on deep eutectic solvent for the HPLC-UV determination of ferulic, caffeic and cinnamic acid from olive, almond, sesame and cinnamon oil, Talanta, 150 (2016) 577-585. [45] T. Tan, M. Zhang, Y. Wan, H. Qiu, Utilization of deep eutectic solvents as novel mobile phase additives for improving the separation of bioactive quaternary alkaloids, Talanta, 149 (2016) 85-90. [46] H. Wang, L. Hu, X. Liu, S. Yin, R. Lu, S. Zhang, W. Zhou, H. Gao, Deep eutectic solvent-based ultrasound-assisted dispersive liquid-liquid microextraction coupled with high-performance liquid chromatography for the determination of ultraviolet filters in water samples, J Chromatogr A, 1516 (2017) 1-8. [47] T. Khezeli, A. Daneshfar, Synthesis and application of magnetic deep eutectic solvents: Novel solvents for ultrasound assisted liquid-liquid microextraction of thiophene, Ultrason Sonochem, DOI 10.1016/j.ultsonch.2016.08.023(2016). [48] T. Khezeli, A. Daneshfar, R. Sahraei, Emulsification liquid-liquid microextraction based on deep eutectic solvent: An extraction method for the determination of benzene, toluene, ethylbenzene and seven polycyclic aromatic hydrocarbons from water samples, J Chromatogr A, 1425 (2015) 25-33.
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ACCEPTED MANUSCRIPT [49] F. Aydin, E. Yilmaz, M. Soylak, A simple and novel deep eutectic solvent based ultrasoundassisted emulsification liquid phase microextraction method for malachite green in farmed and ornamental aquarium fish water samples, Microchemical Journal, 132 (2017) 280-285. [50] F. Aydin, E. Yilmaz, M. Soylak, Vortex assisted deep eutectic solvent (DES)-emulsification liquid-liquid microextraction of trace curcumin in food and herbal tea samples, Food Chem, 243 (2018) 442-447. [51] M.B. Arain, E. Yilmaz, M. Soylak, Deep eutectic solvent based ultrasonic assisted liquid phase microextraction for the FAAS determination of cobalt, Journal of Molecular Liquids, 224 (2016) 538-543. [52] E. Yilmaz, M. Soylak, Ultrasound assisted-deep eutectic solvent based on emulsification liquid phase microextraction combined with microsample injection flame atomic absorption spectrometry for valence speciation of chromium(III/VI) in environmental samples, Talanta, 160 (2016) 680-685. [53] A.H. Panhwar, M. Tuzen, T.G. Kazi, Ultrasonic assisted dispersive liquid-liquid microextraction method based on deep eutectic solvent for speciation, preconcentration and determination of selenium species (IV) and (VI) in water and food samples, Talanta, 175 (2017) 352-358. [54] A.H. Panhwar, M. Tuzen, T.G. Kazi, Deep eutectic solvent based advance microextraction method for determination of aluminum in water and food samples: Multivariate study, Talanta, 178 (2018) 588-593. [55] H. Lores, V. Romero, I. Costas, C. Bendicho, I. Lavilla, Natural deep eutectic solvents in combination with ultrasonic energy as a green approach for solubilisation of proteins: application to gluten determination by immunoassay, Talanta, 162 (2017) 453-459. [56] S. Bajkacz, J. Adamek, Evaluation of new natural deep eutectic solvents for the extraction of isoflavones from soy products, Talanta, 168 (2017) 329-335. [57] T. Bosiljkov, F. Dujmić, M. Cvjetko Bubalo, J. Hribar, R. Vidrih, M. Brnčić, E. Zlatic, I. Radojčić Redovniković, S. Jokić, Natural deep eutectic solvents and ultrasound-assisted extraction: Green approaches for extraction of wine lees anthocyanins, Food and Bioproducts Processing, 102 (2017) 195-203. [58] Y. Huang, F. Feng, J. Jiang, Y. Qiao, T. Wu, J. Voglmeir, Z.-G. Chen, Green and efficient extraction of rutin from tartary buckwheat hull by using natural deep eutectic solvents, Food Chemistry, 221 (2017) 1400-1405. [59] S. Moldoveanu, V. David, Chapter 7 - Solid-Phase Extraction, Modern Sample Preparation for Chromatography, Elsevier, Amsterdam, 2015, pp. 191-286. [60] J. Chen, M. Liu, Q. Wang, H. Du, L. Zhang, Deep Eutectic Solvent-Based MicrowaveAssisted Method for Extraction of Hydrophilic and Hydrophobic Components from Radix Salviae miltiorrhizae, Molecules, 21 (2016). [61] N. Wang, J. Wang, Y. Liao, S. Shao, Preparation of a nitro-substituted tris(indolyl)methane modified silica in deep eutectic solvents for solid-phase extraction of organic acids, Talanta, 151 (2016) 1-7. [62] J.G. X. Zhu, J. Lang, H. Zhang, Y. Zhu, Liquid phase microextarion of Di2 ethylexyl phthalate, International Journal of Innovative Research in Science, Engineering and Technology
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ACCEPTED MANUSCRIPT [65] I. Švancara, K. Vytřas, K. Kalcher, A. Walcarius, J. Wang, Carbon Paste Electrodes in Facts, Numbers, and Notes: A Review on the Occasion of the 50-Years Jubilee of Carbon Paste in Electrochemistry and Electroanalysis, Electroanalysis, 21 (2009) 7-28. [66] A. García, E. Rodríguez-Juan, G. Rodríguez-Gutiérrez, J.J. Rios, J. Fernández-Bolaños, Extraction of phenolic compounds from virgin olive oil by deep eutectic solvents (DESs), Food Chemistry, 197, Part A (2016) 554-561. [67] Z. Helalat-Nezhad, K. Ghanemi, M. Fallah-Mehrjardi, Dissolution of biological samples in deep eutectic solvents: an approach for extraction of polycyclic aromatic hydrocarbons followed by liquid chromatography-fluorescence detection, J Chromatogr A, 1394 (2015) 4653. [68] W. Bi, M. Tian, K.H. Row, Evaluation of alcohol-based deep eutectic solvent in extraction and determination of flavonoids with response surface methodology optimization, J Chromatogr A, 1285 (2013) 22-30. [69] S.M.a.V. David, Modern Sample Preparation for Chromatography, in: S.D. Moldoveanu, V. (Ed.), 2015, pp. 33-51. [70] L. Liu, W. Tang, B. Tang, D. Han, K.H. Row, T. Zhu, Pipette-tip solid-phase extraction based on deep eutectic solvent modified graphene for the determination of sulfamerazine in river water, J Sep Sci, 40 (2017) 1887-1895. [71] K. Vytřas, I. Svancara, R. Metelka, Carbon paste electrodes in electroanalytical chemistry, Journal of the Serbian Chemical Society, 74 (2009) 1021-1033. [72] V.L. Pereira, J.O. Fernandes, S.C. Cunha, Mycotoxins in cereals and related foodstuffs: A review on occurrence and recent methods of analysis, Trends in Food Science & Technology, 36 (2014) 96-136. [73] G. Li, W. Wang, Q. Wang, T. Zhu, Deep Eutectic Solvents Modified Molecular Imprinted Polymers for Optimized Purification of Chlorogenic Acid from Honeysuckle, J Chromatogr Sci, 54 (2016) 271-279. [74] G. Li, T. Zhu, K.H. Row, Deep eutectic solvents for the purification of chloromycetin and thiamphenicol from milk, J Sep Sci, 40 (2017) 625-634. [75] L.U.G. L. H. Keith, J.L.Young, Green Analytical Methodologies, Chem Rev, 107 (2007) 26952708. [76] A. Gałuszka, Z.M. Migaszewski, P. Konieczka, J. Namieśnik, Analytical Eco-Scale for assessing the greenness of analytical procedures, TrAC Trends in Analytical Chemistry, 37 (2012) 61-72.
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Figure Capitations
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Figure 1- Time-trend (2006-2017) representation of the DES and NADES application and their distribution in the different Web Science Categories.
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ACCEPTED MANUSCRIPT Table 1- Density, viscosity, condutivity and spectroscopic polarity index (ETN)of some DES at specific temperatures [3-5,16]
DES (molar ratio)
Density
Viscosity
Condutivity
ET N
Urea:ChCl (2:1)
g/cm 1.25 (25°C)
mm /s 750 (25°C)
(mS cm-1) 0.20 (40°C)
0.84
Ethylene Glycol: ChCl (2:1)
1.12 (25°C)
37 (25°C)
7.61 (20°C)
0.8
Glycerol: ChCl (2:1)
1.18 (25°C)
359 (25°C)
1.05 (20°C )
0.86
Malonic: ChCl (1:1)
1.25 (25°C)
721 (25°C)
1,4- butanediol: ChCl (3:1)
1.06
140 (20°C)
Urea: ethylammonium chloride (1.5:1)
1.041
128 (40 °C )
Acetamide: ethylammonium chloride (1.5:1)
1.14
64 (40 °C)
2,2,2-trifluoroacetamide: ChCl (2:1)
1.342
77 (40 °C)
Water
0.992
1
RI PT
2
0.55 (25°C)
-
1.64 (20°C )
-
-
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(-) not found
-
0.69 (40 °C)
-
0.286 (40 °C)
-
250
1
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ACCEPTED MANUSCRIPT Table 2- Density, viscosity, decomposition temperature (Td) and glass transition temperature (Tg) of some NADES at specific temperatures [4,20]
NADES (molar ratio)
Density (40°C) 3
Viscosity (40°C)
T d/°C
T g/°C
2
mm /s
Fructose: ChCl: water (2:5:5)
1.2078
280.8
160
-84.58
Glucose: ChCl: water (2:5:5)
1.2069
397.4
170
-83.86
Lactic acid: glucose:water (5:1:3)
1.2497
37
135
-77.06
1.14
226.8
176.6
-11.9
Malic acid: ChCl: water (1:1:2)
1.2303
445.9
201
-71.32
Sorbitol: ChCl: water (2:5:6)
1.1854
138.4
>200
-89.62
Sucrose: ChCl: water (1:4:4)
1.2269
581
>200
-82.96
Xylitol: ChCl: water (1:2:3)
1.17841
86.1
>200
-93.33
Water
0.992
SC
Levulinic acid: ChCl (2:1)
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g/cm
1
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ACCEPTED MANUSCRIPT
Techniques LPME LPME
Sample DES - NADES Composition Molar ratio Volume Type ChCl -1,4-butanediol 1:5 2.0 ml Leaves (Chamaecyparis obtusa) ChCl -xylitol 2:1 14 g Olive oil
Extraction amount 200 mg
Time 40 min
14 g
1h
ChCl-urea
1:2
50 µl
Water samples (farm water, rural water, lake water and river water)
50 ml
1 min
AG-DLLME
ChCl-4-Chlorophenol
1:2
190 µl
Fruit and vegetable juice
5 ml
6 min
AAELLME
ChCl-5,6,7,8-Tetrahydro-5,5,8,8tetramethylnaphthalen-2-ol
1:2
100 µl
Water, urine and plasma
Urine added with NaOH solution (2 mol/l) until pH 10 and dilluted to 10 ml with water. The supernatant of 1 ml plasma with 0.5 ml zinc sulfate solution (0.7 mol/l) and 0.1 ml sodium hydroxide solution (1 mol/l) was dilluted to 10 ml with water
HPLME
ChCl-ethylene glycol
1:3
10 µl
HPLME
ChCl-ethylene glycol
1:4
2 µl
Gasoline, diesel fuel, kerosene Leaves of Chamaecyparis obtusa
LPME
Lactic acid–glucose-water
5:1:3
1.5 ml
LPME
Sucrose-ChCl:water
1:4:4
1.5 ml
LPME
Sucrose-ChCl:water
1:4:4
3 ml
Other features
Analyts extracted
Instrumental analysis
Heating 70°C- 30% vol water Heating 40 °C
Flavonoids (myricetin, amentoflavone)
HPLC-UV
Phenolic compounds (hydroxytyrosol, tyrosol, oleacein, oleocanthal, oleuropein agylcon,ligstroside aglycon) 5 mg MMWCNTs, 150 ml Pesticides (alpha-HCH, beta-HCH, acetonitrile, ultrasonic bath gamma-HCH, delta-HCH, heptachlor, aldrin, heptachlor-endo-epoxide, alphaendosulfan, dieldrin, 4,4′ –DDE, endrin, betaendosulfan, 4,4′ –DDD, endrinaldehyde, endosulfan-sulfate, 4,4′ –DDT, endrin-ketone and methoxychlor)
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pH 2; water bath at 40°C for Pesticides (Penconazole, hexaconazole, 3 min, ice and NaCl bath diniconazole, tebuconazole, diazinon, fenazaquin, clodinafoppropargyl, and haloxyfopR-methyl)
LOD Myricetin-0.07 µg/ml; amentoflavone-0.09 µg/ml
Ref. 68 66
GC-ECD
alpha-HCB 0.83 ng/l; beta-HCH 0.20 ng/l; gamma-HCH 0.50 ng/l; delta-HCB-0.17 ng/l; heptachlor0.89 ng/l; aldrin 0.73 ng/l; heptachlor endoepoxide 0.46 ng/l; alpha-endosulfan 0.13 ng/l; dieldrin- 0.10 ng/l; 4,4′ -DDE0.17 ng/l; endrin- 0.17 ng/l; betaendosulfan 0.17 ng/l; 4,4′ -DDD0.17 ng/l; endrin-aldehyde 0.36 ng/l; endosulfan-sulfate 0.43 ng/l; 4,4′ -DDT- 0.73 ng/l; endrinketone- 0.63 ng/l; methoxychlor0.36 ng/l
alpha-HCH 0.25 ng/l; beta-HCH 0.06 ng/l; gamma-HCH 0.15 ng/l; delta-HCH- 0.05 ng/l; heptachlor0.27 ng/l; aldrin- 0.22 ng/l; heptachlor endoepoxide 0.14 ng/l; alpha-endosulfan- 0.04 ng/l; dieldrin- 0.03 ng/l; 4,4′ -DDE 0.05 ng/l; endrin- 0.05 ng/l; betaendosulfan 0.05 ng/l; 4,4′ -DDD 0.05 ng/l; endrin-aldehyde 0.11 ng/l; endosulfan-sulfate 0.13 ng/l; 4,4′ -DDT- 0.22 ng/l; endrinketone- 0.19 ng/l; methoxychlor0.11 ng/l
31
GC-FID
Diazinon 4.2 µg/l; penconazole Diazinon 1.4 µg/l; penconazole 0.75 µg/l; haloxyfop-R-methyl 1.4 0.25 µg/l; haloxyfop-R-methyl µg/l; hexaconazole 0.84 µg/l; 0.45 µg/l; hexaconazole 0.28 µg/l; diniconazole 1.3 µg/l; clodinafop- diniconazole 0.43 µg/l; clodinafoppropargyl 3.9 µg/l; tebuconazole propargyl 1.3 µg/l; tebuconazole 0.64 µg/l; bromopropylate 0.24 1.9 µg/l; bromopropylate 0.71 µg/l; fenazaquin 2.7 µg/l µg/l; fenazaquin 0.90 µg/l
33
pH 10; 100 µl THF; 10 times pulling and pushing
Methadone
GC-FID
0.70 µg/l
2.30 µg/l
34
AC C
EP
3 min
LOQ
HPLC-DAD
SC
DLLME
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Table 3- Summary of the application of DES and NADES in extraction techniques from 2006-2017
Orange petals of Catharanthus roseus Safflower (Carthamus tinctorius L. ) Safflower (Carthamus tinctorius L. )
1 ml
3 min
Ultrasonic bath
Phenolic (phenol, ρ -cresol, β-naphthol)
HPLC-UV
300 mg
30 min
Heating 100 °C ultrasonic irradion 70W
Bioactive terpenoids (Linalool, αterpineol, terpinyl-acetate)
GC-FID
phenol-0.025 µg/l; ρ -cresol-0.05 µg/l; β-naphthol Linalool- 6.687 ng/ml; α-terpineol- Linalool- 2.006 ng/ml; α-terpineol10.50 ng/ml; terpinylacetate3.150 ng/ml; terpinylacetate7.099 ng/ml 2.129 ng/ml
29 28
50 mg
30 min
Stirring at 40 °C
Anthocyanins
UPLC-TOF- M S
39
100 mg
1h
Stirring at 40 °C
HPLC-DAD
37
50 mg
30 min
Stirring at 40 °C
Phenolic compounds (hydro xysafflor Yellow A, cartormin, and carthamin) Colorants (carthamin)
H PLC-DAD
38
ACCEPTED MANUSCRIPT
UAME
DES - NADES Composition Molar ratio Volume ChCl-ethylene glycol 1:2 50 µl
Extraction
Sample Type Olive, almond, sesame and Cinnamon oils
amount 2 ml (1 ml oil -1 ml hexane)
Time 5 min
Other features
Analyts extracted
Instrumental analysis
LOQ
LOD
Ref.
Ultrasonic bath
Phenolic acids (ferulic, caffeic, and cinnamic acids)
HPLC-UV
Ferulic acid -1.30-1.86 µg/l; caffeic acid - 1.43-2.10 µg/l; cinnamic acid 1.60-2.10 µg/l
Ferulic acid -0.39-0.56 µg/l; caffeic acid - 0.43-0.63 µg/l ; cinnamic acid 0.48-0.63 µg/l
44
Cobalt (II)
FAAS
3.60 µg/l
1.1 µg/l
51
FAAS
18.2 µg/l
5.5 µg/l
52
HPLC-UV
Benzene- 21.0 µg/l; toluene- 22.0 µg/l; ethylbenzene-2.90 µg/l; biphenyl- 2.30 µg/l; fluorene- 2.20 µg/l; phenanthrene- 0.30 µg/l; anthracene- 0.06 µg/l; pyrene0.26 µg/l; chrysene- 0.70 µg/l; benzo[a ]pyrene- 0.28 µg/l
Benzene- 6.2 µg/l; toluene- 6.8 µg/l; ethylbenzene-0.8 µg/l; biphenyl- 0.7 µg/l; fluorene- 0.7 µg/l; phenanthrene- 0.09 µg/l; anthracene- 0.02 µg/l; pyrene0.07 µg/l; chrysene- 0.21 µg/l; benzo[a ]pyrene- 0.08 µg/l
48
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Techniques
ChCl-phenol
1:4
500 µl
Tea
Residue resulted of wet digestion (0.5 g) added with 10 ml water
2 min
Ultrasonic bath; pH >6; 1 ml nitroso-2-naphthol; 0.5 ml THF
UALME
ChCl-phenol
1:3
450 µl
Waters (tap, lake, waste)
10 ml
2 min
Ultrasonic bath; 0.375 ml Chromium (III/VI) 0.5M H2SO4; 0.4 ml 0.125% sodium diethyldithiocarbamate; 0.45 ml THF Ultrasonic bath (35 kHz) Thiophene 25°C Ultrasonic bath; 100 µl THF Benzene, toluene, ethylbenezene, PAHs (biphenyl, fluorene, phenanthrene, anthracene, pyrene, chrysene and benzo[a]pyrene )
SC
UALME
ChCl:phenol:FeCl3
1:2:1
25 µl
n-heptane
1.5 ml
5 min
ChCl-phenol
1:2
100 µl
Waters (tap and industrial wastewater)
1.5 ml
20 min
UALME
ChCl-phenol
1:4
500 µl
2 ml
3 min
Ultrasonic bath; pH =3; 500 µl THF
Malachite green
UV-VIS
11.8 µg/l
3.6 µg/l
49
UALME
ChCl-Ox
1:1
1 ml
Waters (farmed and ornamental aquarium fish) Grape skin
100 mg freeze dried skin
50 min
Ultrasonic bath: 65 °C, 35 kHz; 25% water
Phenolics ((+)-Catechin, delphinindin-3O - glucoside, Cyanidin-3-O- glucoside, petunidin-3-O -glucoside, peonidin-3-O glucoside, malvidin-3-O -glucoside, quercetin-3-O -glucoside)
HPLC-UV
(+)-Catechin- 1.24 mg/l, delphinindin-3-O- glucoside- 0.60 mg/l, Cyanidin-3-O-glucoside0.71 mg/l, petunidin-3-Oglucoside- 0.80 mg/l, peonidin-3O-glucoside-0.65 mg/l, malvidin3-O-glucoside - 0.90 mg/l, quercetin-3-O-glucoside -0.46 mg/l
(+)-Catechin- 0.37 mg/l, delphinindin-3-O- glucoside- 0.18 mg/l, cyanidin-3-O-glucoside-0.21 mg/l, petunidin-3-O-glucoside0.24 mg/l, peonidin-3-O-glucoside0.19 mg/l, malvidin-3-O-glucoside - 0.30 mg/l, quercetin-3-Oglucoside -0.05 mg/l
42
UALME
tetramethylammonium chloride–ethylene glycol
1:3
30 µl
Saflower, olive,camellia, colza and soybean oils
1 ml (10 % oil - 90% hexane)
IAA -0.05 µg/ml; IBA -0.06 µg/ml; 4-IPOAA 0.75 µg/ml
45
UALME
Choline Chloride-Laevulinic Acid
1:2
1 ml
Platycladi Cacumen
25 mg
UAME
Choline chloride-malic acid
1:1
1 ml
Wine lees
33.3 mg
UAME
Choline chloride-glycerol
1:1
1 ml
tartary buckwheat hulls
UAME
Fructose-citric acid
1:1
1 ml
UAME
ChCl:citric acid
1.1
600 µl
Raw and processed food (spaghetti, biscuts, and ham) Soy products (soybeans, flour, pasta, breakfast cereals, cutlets, tripe, soy drink, soy nuts, soy cubes and three different dietary supplements)
MAE
ChCl-1,2-propanediol
1:1
10 ml
TE D
GC-FID
47
Ultrasonic bath -50°C
Plant growth regulators ( IAA, IBA, 4IPOAA)
HPLC-UV
30 min
Ultrasonic bath: 50°C, 200 W; 75% water
Flavonoid glycosides and aglycones (myricitrin, quercitrin, amentoflavone, hinokiflavone) Anthocyanins
HPLC-UV
HPLC-DAD
Flavonoid (rutin)
HPLC-UV
58
Gluten
Enzyme Linked ImmunoSorbent Assay
55
Isoflavones (GT, DA, GTGL, daidzin DAGL)
UHPC-UV
DAGL- 0.40 µg/g; GTGL- 0.45 µg/g; DA- 0.25 µg/g; GT 0.20 µg/g
DAGL- 0.12 µg/g; GTGL- 0.14 µg/g; DA- 0.08 µg/g; GT 0.06 µg/g
56
Bioactive compoun ds (ROS, LIT, SAB, SAA, TIIA)
HPLC-DAD
ROS- 0.80 µg/ml; LIT- 1.37 µg/ml; SAB- 1.96 µg/ml; SAA0.87 µg/ml; TIIA- 1.45 µg/ml
ROS- 0.24 µg/ml; LIT- 0.49 µg/ml; SAB- 0.62 µg/ml; SAA- 0.31 µg/ml; TIIA- 0.48 µg/ml
60
EP
7 min
30.6 min
Ultrasaound bath: 341.5 W, 37 kHz, 35°C ; 35.4% water
40 mg
1h
25 mg
15 min
200 mg
60 min
Ultrasaound bath: 20 kHz, 200 W, 40 °C; 20% water Ultrasound bath (100 w 42 kHz) 40% amplitude; 20% water Ultrasonic bath: 440 W, 60°C; 30% water
50 mg
11.11 min
AC C
Radix Salviae miltiorrhizae
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Microwave: 800W, 70°C
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Delphinidin-3-O glucoside- 0.87 Delphinidin-3-O glucoside- 0.28 mg/l; cyanidin-3-O glucosidemg/l; cyanidin-3-O glucoside0.52 mg/l; petunidin-3-O 0.17 mg/l; petunidin-3-O glucoside- 0.44 mg/l; peonidin-3- glucoside- 0.15 mg/l; peonidin-3O glucoside- 0.62 mg/l; malvidin- O glucoside- 0.2 mg/l; malvidin-33-O glucoside- 0.81 mg/l O glucoside- 0.25 mg/l
57
ACCEPTED MANUSCRIPT
UAME
DES - NADES Composition Molar ratio Volume ChCl-ethylene glycol 1:2 50 µl
Extraction
Sample Type Olive, almond, sesame and Cinnamon oils
amount 2 ml (1 ml oil -1 ml hexane)
Time 5 min
Other features
Analyts extracted
Instrumental analysis
LOQ
LOD
Ref.
Ultrasonic bath
Phenolic acids (ferulic, caffeic, and cinnamic acids)
HPLC-UV
Ferulic acid -1.30-1.86 µg/l; caffeic acid - 1.43-2.10 µg/l; cinnamic acid 1.60-2.10 µg/l
Ferulic acid -0.39-0.56 µg/l; caffeic acid - 0.43-0.63 µg/l ; cinnamic acid 0.48-0.63 µg/l
44
Cobalt (II)
FAAS
3.60 µg/l
1.1 µg/l
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FAAS
18.2 µg/l
5.5 µg/l
52
HPLC-UV
Benzene- 21.0 µg/l; toluene- 22.0 µg/l; ethylbenzene-2.90 µg/l; biphenyl- 2.30 µg/l; fluorene- 2.20 µg/l; phenanthrene- 0.30 µg/l; anthracene- 0.06 µg/l; pyrene0.26 µg/l; chrysene- 0.70 µg/l; benzo[a ]pyrene- 0.28 µg/l
Benzene- 6.2 µg/l; toluene- 6.8 µg/l; ethylbenzene-0.8 µg/l; biphenyl- 0.7 µg/l; fluorene- 0.7 µg/l; phenanthrene- 0.09 µg/l; anthracene- 0.02 µg/l; pyrene0.07 µg/l; chrysene- 0.21 µg/l; benzo[a ]pyrene- 0.08 µg/l
48
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Techniques
ChCl-phenol
1:4
500 µl
Tea
Residue resulted of wet digestion (0.5 g) added with 10 ml water
2 min
Ultrasonic bath; pH >6; 1 ml nitroso-2-naphthol; 0.5 ml THF
UALME
ChCl-phenol
1:3
450 µl
Waters (tap, lake, waste)
10 ml
2 min
UALME
ChCl:phenol:FeCl3
1:2:1
25 µl
n-heptane
1.5 ml
5 min
UALME
ChCl-phenol
1:2
100 µl
Waters (tap and industrial wastewater)
1.5 ml
20 min
Ultrasonic bath; 0.375 ml Chromium (III/VI) 0.5M H2 SO4 ; 0.4 ml 0.125% sodium diethyldithiocarbamate; 0.45 ml THF Ultrasonic bath (35 kHz) Thiophene 25°C Ultrasonic bath; 100 µl THF Benzene, toluene, ethylbenezene, PAHs (biphenyl, fluorene, phenanthrene, anthracene, pyrene, chrysene and benzo[a]pyrene)
UALME
ChCl-phenol
1:4
500 µl
2 ml
3 min
Ultrasonic bath; pH =3; 500 µl THF
Malachite green
UV-VIS
11.8 µg/l
3.6 µg/l
49
UALME
ChCl-Ox
1:1
1 ml
Waters (farmed and ornamental aquarium fish) Grape skin
100 mg freeze dried skin
50 min
Ultrasonic bath: 65 °C, 35 kHz; 25% water
Phenolics ((+)-Catechin, delphinindin-3O - glucoside, Cyanidin-3-O- glucoside, petunidin-3-O -glucoside, peonidin-3-O glucoside, malvidin-3-O -glucoside, quercetin-3-O -glucoside)
HPLC-UV
(+)-Catechin- 1.24 mg/l, delphinindin-3-O- glucoside- 0.60 mg/l, Cyanidin-3-O-glucoside0.71 mg/l, petunidin-3-Oglucoside- 0.80 mg/l, peonidin-3O-glucoside-0.65 mg/l, malvidin3-O-glucoside - 0.90 mg/l, quercetin-3-O-glucoside -0.46 mg/l
(+)-Catechin- 0.37 mg/l, delphinindin-3-O- glucoside- 0.18 mg/l, cyanidin-3-O-glucoside-0.21 mg/l, petunidin-3-O-glucoside0.24 mg/l, peonidin-3-O-glucoside0.19 mg/l, malvidin-3-O-glucoside - 0.30 mg/l, quercetin-3-Oglucoside -0.05 mg/l
42
UALME
tetramethylammonium chloride–ethylene glycol
1:3
30 µl
Saflower, olive,camellia, colza and soybean oils
1 ml (10 % oil - 90% hexane)
IAA -0.05 µg/ml; IBA -0.06 µg/ml; 4-IPOAA 0.75 µg/ml
45
UALME
Choline Chloride-Laevulinic Acid
1:2
1 ml
Platycladi Cacumen
25 mg
UAME
Choline chloride-malic acid
1:1
1 ml
Wine lees
33.3 mg
UAME
Choline chloride-glycerol
1:1
1 ml
tartary buckwheat hulls
UAME
Fructose-citric acid
1:1
1 ml
UAME
ChCl:citric acid
1.1
600 µl
Raw and processed food (spaghetti, biscuts, and ham) Soy products (soybeans, flour, pasta, breakfast cereals, cutlets, tripe, soy drink, soy nuts, soy cubes and three different dietary supplements)
MA
ChCl-1,2-propanediol
1:1
10 ml
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GC-FID
47
Ultrasonic bath -50°C
Plant growth regulators (IAA, IBA, 4IPOAA)
HPLC-UV
30 min
Ultrasonic bath: 50°C, 200 W; 75% water
Flavonoid glycosides and aglycones (myricitrin, quercitrin, amentoflavone, hinokiflavone) Anthocyanins
HPLC-UV
HPLC-DAD
Flavonoid (rutin)
HPLC-UV
58
Gluten
Enzyme Linked ImmunoSorbent Assay
55
Isoflavones (GT, DA, GTGL, daidzin DAGL)
UHPC-UV
DAGL- 0.40 µg/g; GTGL- 0.45 µg/g; DA- 0.25 µg/g; GT 0.20 µg/g
DAGL- 0.12 µg/g; GTGL- 0.14 µg/g; DA- 0.08 µg/g; GT 0.06 µg/g
56
Bioactive compou nds (ROS, LIT, SAB, SAA, TIIA)
HPLC-DAD
ROS- 0.80 µg/ml; LIT- 1.37 µg/ml; SAB- 1.96 µg/ml; SAA0.87 µg/ml; TIIA- 1.45 µg/ml
ROS- 0.24 µg/ml; LIT- 0.49 µg/ml; SAB- 0.62 µg/ml; SAA- 0.31 µg/ml; TIIA- 0.48 µg/ml
60
EP
7 min
30.6 min
Ultrasaound bath: 341.5 W, 37 kHz, 35°C ; 35.4% water
40 mg
1h
25 mg
15 min
200 mg
60 min
Ultrasaound bath: 20 kHz, 200 W, 40 °C; 20% water Ultrasound bath (100 w 42 kHz) 40% amplitude; 20% water Ultrasonic bath: 440 W, 60°C; 30% water
50 mg
11.11 min
AC C
Radix Salviae miltiorrhizae
SC
UALME
Microwave: 800W, 70°C
43
Delphinidin-3-O glucoside- 0.87 Delphinidin-3-O glucoside- 0.28 mg/l; cyanidin-3-O glucosidemg/l; cyanidin-3-O glucoside0.52 mg/l; petunidin-3-O 0.17 mg/l; petunidin-3-O glucoside- 0.44 mg/l; peonidin-3- glucoside- 0.15 mg/l; peonidin-3O glucoside- 0.62 mg/l; malvidin- O glucoside- 0.2 mg/l; malvidin-33-O glucoside- 0.81 mg/l O glucoside- 0.25 mg/l
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ACCEPTED MANUSCRIPT
Time Simplicity + ++ ++ + ++ + + + ++ + ++
Low Solvent Volume + + ++ ++ ++ ++
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(-), less favourable; (+), favourable; (++), more favourable
Cost + + ++ + + -
Common instrument analysis HPLC HPLC and GC HPLC and GC HPLC and GC HPLC, spectrophotometry, Immunoassay HPLC
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Technique LPME DLLME AG-DLLME and AAELLME HPLME UAME MAE
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Table 4- Overall performance of extraction techniques based on the use DES/NADES solvents Greenness + + + + ++ +
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LPME, liquid-phase microextraction; DLLME, dispersive liquid-lquid microextraction; AG-DLLME, gas air-dispersive liqui-lquid microextraction; AAELLME,air-assisted liquid-liquid microextraction; HPLME, hollow fiber-liquid phase microextraction; UAME, ultrasound-assisted microextraction; MAE, microwave-assisted Extraction; HPLC, high performance liquid chromatography; GC, gas chromatography
ACCEPTED MANUSCRIPT
Fig 1 18 16 14 12 10 8 6
100 50 0
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
year
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Web of Science Categories ENERGY FUELS ELECTROCHEMISTRY CHEMISTRY ANALYTICAL
EP
THERMODYNAMICS PHYSICS ATOMIC MOLECULAR CHEMICAL
GREEN SUSTAINABLE SCIENCE TECHNOLOGY ENGINEERING CHEMICAL CHEMISTRY PHYSICAL CHEMISTRY MULTIDISCIPLINARY 0
5
10
15
20
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
year
Web of Science Categories
Chemistry AppliedCHMEISTRY APPLIED BIOCHEMISTRY MOLECULAR BIOLOGY PLANT SCIENCES FOOD SCIENCE TECHNOLOGY CHEMISTRY MEDICINAL GREEN SUSTAINABLE SCIENCE…
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MATERIALS SCIENCE MULTIDISCIPLINARY
4 2 0
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450 400 350 300 250 200 150
Number of publications
500
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Number of publications
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PHARMACOLOGY PHARMACY ENGINEERING CHEMICAL CHEMISTRY ANALYTICAL CHEMISTRY MULTIDISCIPLINARY 25
30
35
% of publication from a total of 1303
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5
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20
25
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ACCEPTED MANUSCRIPT Highlights DES and NADES are environmentally-friendly alternative to organic solvents Novel applications of DES and NADES in microextraction techniques for food, biological and environmental analysis are described Recent microextraction techniques based in DES/NADES are compared with earlier approaches
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Future perspectives of DES/NADES in microextraction techniques are stated
S0165-9936(18)30118-3
DOI:
10.1016/j.trac.2018.05.001
Reference:
TRAC 15145
To appear in:
Trends in Analytical Chemistry
Received Date: 12 March 2018 Revised Date:
1 May 2018
Accepted Date: 1 May 2018
Please cite this article as: S.C. Cunha, J. Fernandes, Extraction techniques with deep eutectic solvents, Trends in Analytical Chemistry (2018), doi: 10.1016/j.trac.2018.05.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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USAEME
OTHER
MAE
NADES
ACCEPTED MANUSCRIPT 1
Extraction techniques with deep eutectic solvents
2
Sara C. Cunha* and José Fernandes*
3 *Corresponding author:
5 6
José O. Fernandes and Sara C. Cunha: Tel: +351-220428639; Fax: +351-226093390; E-mail: [email protected], [email protected].
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LAQV-REQUIMTE, Laboratório de Bromatologia e Hidrologia, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
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ACCEPTED MANUSCRIPT 11
ABSTRACT In last years, a plethora of extraction techniques has emerged as environmental-
13
friendly alternatives to conventional extraction procedures. In this particular field, a
14
novel class of solvents known as deep eutectic solvents (DES) has arisen as a new
15
and very promising tool. Compared with conventional organic solvents, DES as well as
16
the so-called natural deep eutectic solvents (NADES) have attracted considerable
17
attention due to the fact that they not only are eco-friendly, non-toxic, and
18
biodegradable organic compounds but also have a low cost, being easy to produce in
19
the own laboratory. The present review provides a critical and organized overview of
20
novel extraction techniques using DES as extracting solvents that were applied in food,
21
biological and environmental sample analysis. An evaluation of how these
22
DES/NADES could improve extraction yields of a variety of analytes and advantages
23
and limitations of each proposal will be discussed and compared with earlier studies.
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Keywords: Sample Preparation, Deep Eutectic Solvents, Natural Deep Eutectic Solvents, extraction, Chemical Analysis
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ACCEPTED MANUSCRIPT Abbreviations: AALLME, air-assisted liquid-liquid microextraction, AA-DLME, air-
28
assisted dispersive liquid-liquid microextraction, AAS, flame atomic absorption
29
spectrometry AAS, CPEs, carbon paste electrodes, DA, daidzein, DAGL, daidzin,
30
DEHP, di(2-ethylhexyl)phthalate, DLLME, dispersive liquid-liquid microextraction, DNA,
31
Deoxyribonucleic acid, ELISA, Enzyme-Linked Immunosorbent Assay, FAAS, flame
32
atomic absorption spectrometry, FT-IR, fourier-transform infrared spectroscopy, GA-
33
DLLME, gas air-dispersive liqui-lquid microextraction, GC-ECD, gas chromatography-
34
electron capture detector, GC-FID, gas chromatography- flame ionization detector, GT,
35
genistein, GTGL, genistin, HBA, hydrogen-bond acceptor, HBD, hydrogen-bond donor,
36
HPLC-DAD, high performance liquid chromatography- diode array detection, HPLC-
37
UV, high performance liquid chromatography-ultraviolet, HS-SME, headpsace solid-
38
single microextraction, HF-LPME, hollow fiber-liquid phase microextraction IAA, Indole-
39
3-acetic acid, IBA, 3-indolebutyric acid, 4-IPOAA, 4-iodophenoxyacetic acid, LGH,
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lactic acid–glucose, LIT, lithospermic acid, LPME, liquid phase microextraction, MAE,
41
microwave-assisted extraction, MAME microwave microextraction, MDES, magnetic
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deep eutectic solvents, MIPs, Molecularly imprinted polymers, MMWCNT, magnetic
43
multi-walled carbon nanotube nanocomposite, NIPs, non-imprinted polymers, NMR,
44
nuclear magnetic resonance, OCPs, organochlorine pesticides Ox, oxalic acid,
45
PAHs, polycyclic aromatic hydrocarbons, PDA, photodiode array, PCH, 1,2-
46
propanediol–choline chloride, PT-SPE, pipette-tip solid-phase extraction, ROS,
47
rosmarinic acid, RSD, relative standard deviation,
48
salvionalic
49
microextraction, S-SIL-MSPD silica-supported ionic liquid-based matrix solid phase
50
dispersion, SPE, solid-phase extractions, UAE, ultrasound-assisted extraction,
51
UHPLC-UV, ultra-high performance liquid chromatography with ultraviolet detection,
52
UAME, ultrasound assisted microextraction, UALPME ultrasound assisted liquid phase
53
microextraction USAEME, ultrasound-assisted emulsification microextraction, UPLC-
54
TOF-MS, Ultra Performance Liquid Chromatography-Time-of-flight Mass Spectrometry,
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acid,
SDME,
single
drop
SAA, salvionalic acid A, SAB,
microextraction,
SPME,
solid-phase
3
ACCEPTED MANUSCRIPT UV-VIS,
ultraviolet-visible
spectrophotometry,
56
tetrahydrofuran, VWD, variable wavelength detector.
TIIA,
tanshinone
IIA,
THF,
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4
ACCEPTED MANUSCRIPT 1. INTRODUCTION
58
Sample preparation is a common step in trace analytical methods, involving the
59
extraction of an analyte or a class of analytes from its original matrix into a solvent in
60
order to allow its further analysis by a sensitive and selective way. Conventional
61
sample preparation techniques such as multi-step liquid-liquid extraction, Soxhlet
62
extraction and solid-phase extraction, among others, are usually time-consuming, labor
63
intensive and involve the use of a large volume of organic solvents, which is expensive
64
and generate a considerable amount of waste harmful for human health and the
65
environment. To overcome these drawbacks, numerous efforts have been made over
66
the last decades, to streamline sample extraction procedures and also to reduce or
67
eliminate the use or generation of hazardous substances in agreement with the
68
principles of the green chemistry [1]. New techniques miniaturizing solid-phase
69
extraction or liquid-liquid extraction have appeared such as SPME and LPME,
70
respectively. SPME is a solventless extraction technique very popular in recent years
71
that use different fiber materials in various configurations for the extraction of a wide
72
range of volatile analytes [2]. LPME comprises a range of slightly different techniques
73
characterized by using low amounts of sample matrices and small volumes of organic
74
solvents. Often it can employ different types of kinetic energy such as ultrasound
75
(UAME) or microwave (MAE) in order to improve extraction efficiency, enrichment
76
factor and simultaneously reduce extraction time. Progresses made in the last decade
77
(2006-2017) in the field of sample extraction are confirmed by the increasing number of
78
published scientific articles on SPME, LPME, UAME and MAE. In the ISI Web of
79
knowledge there are references for that period of about 11,133 published scientific
80
papers on SPME, 1,351 on LPME, 1,790 on UAME and 2,803 on MAE for
81
determination of different organic and inorganic compounds, of which more than 60%
82
were published in the last five years. The keywords used for this research were: “solid-
83
phase microextraction”, “liquid phase microextraction”, “ultrasound assisted extraction”
84
and “microwave-assisted extraction”.
85
Until some years ago, solvents used in LPME techniques were always associated with
86
a certain degree of toxicity, but the recent development of a remarkable generation of
87
new extracting solvents, i.e. DES is changing this scenario. These solvents are
88
commonly composed of two non-toxic components, one of them with capacity to be a
89
HBA (quaternary ammonium, tetralkylammonium or phosphonium salts) while the other
90
(acids, alcohols, amines and carbohydrates) possess HBD properties [3]. Generally,
91
DES have much lower melting point than that of any of its individual components,
92
which is due to the formation of intramolecular hydrogen bonds [4], and possess some
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ACCEPTED MANUSCRIPT noteworthy chemical properties, such as low vapor pressure, relatively wide liquid-
94
range, non-flammability and unreactivity towards water [5]. Moreover, DES are easy to
95
be prepared not requiring purification steps, are made from low cost compounds,
96
present low or negligible toxicity and are biodegradable and easily recyclable. These
97
features make DES preferable over the conventional solvents used in extraction
98
procedures.
99
Similar properties to DES have the so-called NADES, solvents which are prepared
100
using natural components produced by cell metabolism. Based on the hypothesis that
101
the existence of NADES in living organisms can explain many biological processes,
102
several NADES composed of simple molecules always present in living cells (urea,
103
amino acids, sugars and choline) have been synthesised and studied in what respect
104
their solvent properties [6].
105
Indeed, DES and NADES showed to have excellent potential as extracting solvents in
106
several sample preparation procedures such as LPME, UAME and MAE. Literature
107
research in ISI Web of knowledge indicates a total of 1,303 references about DES and
108
56 regarding NADES, of which 321 and 31, respectively, are related with extraction
109
procedures. Since 2011 the number of publications has increased considerably, arising
110
462 in 2017, 443 of which related to DES and 19 to NADES (Figure 1). According to
111
the Web Science Categories, most of these references are within the scope of
112
multidisciplinary chemistry, followed by chemistry physical or chemistry analytical,
113
respectively. The reason for the increase number of publications in the analytical field
114
can be attributed to the unique features of these new liquids such as high thermal
115
stability, low thermal conductivity, low volatility and adjustable miscibility as well as the
116
capacity to be combined with advanced separation techniques like HPLC and GC. The
117
present review, cover applications reported until the end of 2017 and is mainly focused
118
on microextraction techniques using DES/NADES as extracting solvents for food,
119
biological and environmental sample analysis. The potential of each modern extraction
120
technique will be discussed and compared with earlier studies and an evaluation of
121
how these techniques could improve extraction efficiency for a variety of analytes will
122
be made.
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2. DEEP EUTECTIC SOLVENTS (DES): A BRIEF OVERVIEW
125
In the year of 2001, Abbot and co-workers reported that a mixture of a choline chloride
126
and a metal salt (zinc chloride) could form a liquid, at temperatures below 100°C [7].
127
Two years later, the same group developed a mixture of ChCl with an hydrogen-bond 6
ACCEPTED MANUSCRIPT donor (urea) [8] designating it as DES. In the subsequent years other DES have been
129
reported namely that formed by mixing ChCl with different carboxylic acids (oxalic,
130
malonic, and succinic acids) [9]. Another major family of DES that have been widely
131
explored are those that combine a carbohydrate (or a reduced derivative as is the case
132
with sorbitol and mannitol), an urea derivative (N,N’-dimethylurea), and a chloride salt
133
(ammonium chloride)[10]. Generally, the melting point of the DES is lower than the
134
melting points of each of its starting components. One of the attractive features of
135
these novel solvents is the possibility of having, simply by changing one or both
136
components, a huge number of eutectic mixtures with different chemical properties.
137
Recently, a new class of DES have been synthetized, based on combinations of
138
decanoic acid with various quaternary ammonium salts [11] or DL-menthol with several
139
natural acids [12]. This new class of DES showed a high hydrophobic behavior in
140
contrast to the previous hydrophilic DES [11]. Many extraction procedures can become
141
more effective by using these hydrophobic DES due their capability of extracting
142
analytes hydrophobic from aqueous solutions. Additionally, these new solvents have
143
the ability to extract both dissociated and undissociated forms of acidic compounds,
144
broadening the application of hydrophobic DES for different pH environments [11].
145
DES are easily produced by just mixing two or more compounds and heating them to
146
around 80 °C [8, 13] or freeze-drying [14], without the subsequent need of any complex
147
purification step, thus reaction conditions are accessible for any laboratory. However,
148
owing to the extreme hygroscopicity of the HBA (e.g. ChCl, tetrabutylammonium, DL-
149
menthol), attracting moisture to preparations, a careful manipulation through using
150
vacuum conditions is advised. Although ChCl is the most employed quaternary
151
ammonium salt because of its low cost and biodegradability (it is indeed produced in
152
large scale and added to the chicken feed as nutrient), many other halides
153
(methyltriphenylphosphonium
154
acetylcholine chloride, tetramethylammonium chloride among others) are suitable for
155
making DES [5].
156
One of the main features of DES is their possibility to be used as extracting solvent for
157
a wide range of chemical different solutes [3]. Their uses as solvents in extraction
158
procedures depends on their physical properties, such as viscosity, density, miscibility
159
and polarity. It is convenient to select solvents with low viscosity to facilitate mixing but
160
with a large density difference from the matrix in order to easy the separation of phases
161
[15]. The main physical properties of DES including freezing point, density, viscosity,
162
conductivity, and polarity are briefly discussed below in this section and some DES are
163
highlighted in Table 1. More detailed information on the properties of DES can be
bromide,
benzyltriphenylphosphonium
chloride,
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ACCEPTED MANUSCRIPT found in recent reviews by Zang et al. [3], Tang and Row [16], Smith et al. [5], and
165
references cited therein.
166
The DES freezing point is dependent on DES components (type of HBD and HBA) and
167
its molar ratio. For instance, the freezing point of a choline salt-derived DES combined
168
with urea decreases in the order F- > NO3- > Cl- > BF4- indicating a correlation with the
169
hydrogen bond strength [3, 17]. The organic salt/HBD molar ratio has also significant
170
effect on the freezing point of a DES. For instance, when ChCl was mixed with urea in
171
a molar ratio of 1:1 and 1:2, the resulting DES showed a freezing point >50 °C and 12
172
°C, respectively [3].
173
DES exhibit in general higher density values than water with levels ranging from 1.041
174
g cm-3 to 1.63 g cm-3 [3]. This feature helps the rapid settling of DES phase in phase
175
separation devices used in DLLME techniques.
176
Most of the DES exhibit a relatively high viscosity at room temperature (> 100 cP) [3].
177
This can be of substantial benefit when carrying out SDME, as the high viscosity
178
facilitates the suspension of larger drops at the tip of a needle. However, in some
179
extraction procedures such as DLLME this characteristic can affect negatively the
180
diffusion of analytes. To surpass this drawback some authors, increase the
181
temperature during extraction or, alternatively, increase the ChCl concentration, which
182
are reported in literature to reduce the viscosity of some eutectic mixtures.
183
In general, DES show poor conductivity (lower than 2 mS cm-1 at room temperature) [3]
184
due to their high viscosity. However, conductivities of DES increase significantly as the
185
temperature increases due to a decrease of the respective viscosity [3, 17, 18].
186
Furthermore, the successive addition of ChCl to glycerol lowers the viscosity and
187
increases the conductivity (from 0.74 mS cm-1 for a molar ratio of 1-4 ChCl˗glycerol to
188
1.30 mS cm-1 for a molar ratio of 1-2 ChCl˗glycerol) [18] due to more available charge
189
carriers in an increasingly less viscous solvent.
190
Polarity is one of the most important distinguishing characteristics of DES, in view of
191
their extraction ability and their miscibility with other solvents. Nevertheless, few studies
192
related to DES polarity are published. Abbott and co-workers reported that the polarity
193
scale of ChCl-glycerol was similar to RNH3+X-, R2NH2+X-, and imidazolium ionic liquids
194
[17, 18]. In DES composed of an ammonium salt and carboxylic acids the acidity is
195
mainly provided by the organic acid present in the mixture, and an increase of the alkyl
196
side chain of both compounds leads to a lower ability of the solvent to donate protons
197
[19]. Carbohydrate derivative DES present higher polariry than those observed for
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short chain alcohols (e.g. ethanol, 2-propanol) and some polar aprotic solvents (e.g.
199
dimethylsulfoxide and dimethylformamide) [10].
200 3. NATURAL DEEP EUTECTIC SOLVENTS: A BRIEF OVERVIEW
202
Recently, Choi and collaborators have explored natural products as a source of DES
203
solvents, including primary metabolites common in living cells (sugars, sugar alcohols,
204
organic acids, amino acids, amines) as well as water [6]. NADES can be obtained by
205
heating a mixture of two or three components in certain molar ratios in the presence of
206
water, which decrease their viscosity and allows the occurrence of extensive inter
207
molecular interactions e.g. H-bonds or ionic bonds [20](Table 2). The usually
208
components of NADES as HBA are amines (ChCl, ammonium chloride) or amino acids
209
(alanine, proline, glycine, betain) while as HBD the more common are organic acids
210
(oxalic acid, lactic acid, malic acid, etc.) or carbohydrates (glucose, fructose, maltose,
211
etc.).
212
As a whole NADES possess excellent properties as solvents [20], e.g., negligible
213
volatility, a very low melting point (they are liquid even below -20 oC), a broad polarity
214
range and high solubilization power of a wide range of compounds, especially poorly
215
water-soluble compounds [6, 20]. The high solubility of scarce water-soluble
216
metabolites and macromolecules (e.g. DNA, proteins, cellulose, and amino acids) has
217
been demonstrated [20-22] as well as their suitability as media for enzymatic reactions
218
[6, 23] and biotransformations [24]. It was verified that NADES composed by 1 mol of
219
ChCl and 2 mol of 1,2-ethanediol, glycerol, malonic acid, or urea, the two first present a
220
more dipolar nature than the last ones, which can be attributed to the presence of
221
alcohol functionalities on 1,2-ethanediol and glycerol [25]. Despite this data, detailed
222
information about chemical and physical properties is still scarce, and only few
223
applications involving NADES in the analytical field, e.g. extraction of organic
224
compounds, are reported. Therefore, a deep research on the preparation of NADES for
225
specific applications is still required.
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226 227
4. LIQUID-PHASE MICROEXTRACTION
228
LPME extraction procedures correspond to efficient alternatives to traditional liquid-
229
liquid extraction, offering numerous advantages such as a high degree of concentration
9
ACCEPTED MANUSCRIPT (or enrichment factor), and low consumption of organic solvents while requesting
231
minute amounts of samples.
232
In LPME techniques, usually few microliters of the extracting solvent (usually
233
designated as acceptor phase) are placed directly into the aqueous sample containing
234
analytes (donor phase) or in its headspace and later the extracting solvent is collected.
235
In the last few years numerous LPME procedures have been developed such as
236
SDME, HF-LPME and DLLME. In SDME a drop of extractive solvent is suspended in
237
the tip of a syringe which can be immersed in the aqueous phase of the sample or
238
exposed to the respective headspace (HS-SME). In HF-LPME the extracting phase is
239
placed inside the lumen of a porous polypropylene hollow fiber, to improve the stability
240
and reliability of extraction [26]. In DLLME a cloudy solution of small droplets of
241
extracting solvent (microliters of a water-immiscible high density organic solvent) is
242
formed and dispersed throughout the aqueous phase using a dispersive solvent,
243
miscible in both extracting and aqueous phases. Currently some DLLME procedures
244
do not require the use of dispersive solvent being in those cases the cloud solution
245
obtained either by the injection of air bubbles (GA-DLLME), formation of air bubbles
246
using a vortex, or by the mechanic action of sucking and injecting the aqueous solution
247
with a syringe (AALLME and AA-DLME). Overall, in all these procedures, extraction
248
efficiency is dependent of many factors such as partition coefficient, type and volume of
249
extracting and dispersive solvents, sample volume, analyte properties, agitation, ionic
250
strength, extraction time, temperature, etc. A detailed discussion of the importance of
251
each parameter can be found in the literature [27].
252
LPME techniques using DES or NADES as extracting solvent had been used for
253
extraction of several polar nonvolatile and volatile compounds from food and water
254
matrices (Table 3).
255
Tang et al. [28] optimized a two phase HS-SME technique where a DES (ChCl and
256
ethylene glycol, 1:4 molar ratio) drop suspended in a tip of a microsyringe needle was
257
exposed for 30 min to the headspace of leaf samples to extract bioactive terpenoids.
258
The use of a 2 µl DES drop was enough to allow the adsorption of the target
259
compounds volatilized from the samples heated at 100 °C and ultrasonicated at 70 W.
260
Once stopped the procedure, the suspended drop was retracted back into the
261
microsyringe and injected into a GC-FID.
262
In the same year 2014, Gu et al. [29] employed a similar HS-SME procedure for the
263
extraction of phenolic compounds from crude oils; they also used ChCl and ethylene
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ACCEPTED MANUSCRIPT glycol (1:3, molar ratio) as DES and ultrasonication to reduce the extraction time
265
needed and to improve the yields [29].
266
A three phase HS-SME procedure using DES (methyltriphenylphosphonium iodide and
267
ethylene glycol, 1:4 molar ratio) plus 20% v/w methanol as an acceptor phase and n-
268
dodecane as extraction solvent was applied to extract steroidal hormones
269
(dydrogesterone and cyproterone acetate) from biological samples (urine and plasma)
270
[30]. The analytes were further analyzed by LC-UV, and the obtained performance in
271
what respect range of linearity and LOD have compared positively to those reported in
272
literature using more sensitive detectors.
273
Recently, Yousefi et al.[31] developed a two phase HS-SME procedure using an
274
hydrophobic magnetic bucky gel formed by combining DES (ChCl:chlorophenol, 1:2
275
molar ratio) and magnetic multiwalled carbon nanotubes for the extraction of volatile
276
hydrocarbons from water and urine samples. The extraction was successfully
277
completed in 10 min using a drop of 20 µL that was placed in the headspace of the vial
278
containing the aqueous sample. The extraction temperature was kept at 30 °C and the
279
vial was stirred at 1200 rpm. The use of a large drop compared with other HS-SME
280
based DES procedure showed to provide a higher sensitivity. When compared with
281
conventional solvents DES showed more adequate to form stable drops for HS-SME
282
due to its higher thermal stability, higher viscosity, lower volatility and adjustable
283
miscibility.
284
Concerning to DLLME conventional process using DES as extracting solvent it was
285
used just by Ferrone et al. [32] for determination of oxyprenylated, phenylpropanoids in
286
vegetable oils. The extraction was performed with 45 µL of DES (phenylacetic acid:
287
betaine, 2:1 molar ratio) and isopropanol (200 µL) as dispersive solvent; following
288
agitation and centrifugation, 5 µL of the bottom phase were injected in a UHPLC-PDA
289
system. This method allowed the achievement of good limits of detection, linearity and
290
reproducibility similar or better to those reported in literature for the same analytes.
291
A novel rapid and efficient GA-DLLME procedure characterized by the absence of
292
dispersive solvent was developed by Farajzadeh et al. [33] for the extraction of 9
293
pesticide residues from fruit and vegetable juices. In the optimized extraction
294
procedure, air was bubbled into a test tube to disperse the extracting DES (ChCl: 4-
295
chlorophenol, 1:2 molar ratio) into the aqueous solution, in order to obtain a cloudy
296
solution. After centrifugation, an aliquot of the sedimented phase is injected into GC-
297
FID for the separation and determination of the enriched pesticide residues [33].
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ACCEPTED MANUSCRIPT Another new type of DLLME is the AALLME. Similar to GA-DLLME, in this technique
299
the cloud solution is obtained by sucking and injecting several times the mixture of
300
extracting solvent and aqueous sample. Lamei et al. [34] used this technique
301
employing a mixture of ChCl and 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ol
302
(1:2 molar ratio) as DES extractor and THF as a demulsifier agent, for the extraction of
303
methadone from water and biological samples. Therefore, the dispersion of the
304
aggregated DES droplets into aqueous phase was achieved by the effect of sucking
305
and injecting (10 times) the mixture of sample, extracting solvent and demulsifier agent.
306
After a brief centrifugation the uplayer was directly analyzed by GC-FID. A pronounced
307
advantage in comparison to the other LPME described in the literature for methadone
308
extraction is the low toxicity and low cost of the extracting solvent used.
309
AA-DLLME was developed and optimized by Ge et al. [35] for pre-concentration and
310
separation of 6 benzophenones from different types of waters. Using a hydrophobic
311
DES (mixture of DL-menthol and decanoic acid, 2:1 molar ratio) as extractor solvent,
312
which was several times injected into the aqueous solutions, the authors were able to
313
extract efficiently the benzophenones without the use of dispersive solvents.
314
In a similar way, Zheng et al. [36] used a hydrophobic DES with 1-decyl-3-
315
methylimidazolium chloride and 1-dodecanol (1:2, molar ratio) for the extraction of
316
benzoylureas from waters, followed by HPLC-UV analysis. Various conditions were
317
optimized, namely the type and volume of extractor, salt addition, vortex time,
318
temperature of extraction and pH of the aqueous sample. The authors concluded that
319
8.0 mL of sample solution with 450 mg sodium chloride and pH at 4-6 provided the best
320
recoveries when extracted with 40 µL of DES during 3 min in vortex at 40 °C.
321
Since the discovery of NADES by the Choi group [6] several works have been
322
published by the same research group exploring the potential of NADES as solvents to
323
extract bioactive compounds such as antocyanins, and phenols from several solid
324
samples (Table 3) [20, 37, 38]. In general, a low amount of sample (<100 mg) is
325
extracted with a small volume of the chosen NADES (< 3 ml) at controlled temperature
326
(40 ºC) using vortex stirring. A pronounced advantage of the use of NADES in LPME in
327
comparison to the conventional extracting solvents is the higher stability of the extract
328
obtained and, of course, the use of a solvent sustainable and environmental-friendly.
329
In 2013, Dai et al. [20] tested different NADES and a multivariate data analysis to
330
demonstrate that the extractability of a wide range of phenolic compounds (hydrophilic
331
and hydrophobic metabolites of safflower) were greater with NADES than with
332
conventional solvents. This high extractability was attributed to H-bonding interactions
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ACCEPTED MANUSCRIPT between molecules of NADES and phenolic compounds. In 2014 the same group
334
continued the previous work, exploring the ability of different NADES to stabilize
335
unstable phenolic compounds extracted from safflower such as carthamin [38]. They
336
found that carthamin is more stable in glucose-ChCl and sucrose-ChCl than in acidic
337
NADES such as proline-malic acid or lactic-acid-glucose and the stabilization aptitude
338
of NADES increases with increasing viscosity (low water content). Lately, Dai et al [39]
339
tested diverse NADES for the extraction of anthocyanins from purple and orange petals
340
of Catharanthus roseus. Among the NADES evaluated, LGH and PCH showed to
341
present a similar extraction power for anthocyanins as conventional organic solvents,
342
with the additional advantage exhibited by LGH to provide at least three times higher
343
stability capacity for cyanidins than acidified ethanol, facilitating their extraction and
344
further analysis by UPLC-TOF-MS.
345
These works clearly showed that both DES and NADES have a high potential as
346
extracting solvents for a wide range of analytes of low to medium polarity and
347
demonstrated a bright future for the application of these novel classes of extracting
348
solvents in LPME field.
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5. ULTRASOUND ASSISTED MICROEXTRACTION
351
In UAME techniques the extraction procedure takes place under ultrasonic energy
352
(typical systems use a frequency energy of 40 kHz), which favors the contact between
353
sample and extracting solvent. Ultrasounds radiation can be applied by means of
354
water-baths or ultrasonic probes, being the last ones able to deliver higher energy input
355
per volume due to a more focused and uniform power input. Conversely, ultrasonic
356
probes provide an entire control over the most important sonication parameters,
357
leading to more reproducible results [40].
358
In general, extraction efficiency of UAME techniques depends on different factors such
359
as extracting solvent (type, pH, volume), ultrasonic conditions (temperature, amplitude
360
of sonication, sonication time), and sample features (matrix, amount, particle size) [40,
361
41].
362
The main advantage of using UAME compared with conventional DLLME is that no
363
dispersive solvent is needed to achieve a high surface area of contact between the
364
extracting solvent and sample. Additionally, UAME can promote a greater penetration
365
of the extracting solvent in solid samples matrices.
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367
liquid samples, although their application to solid samples or to the extraction of
368
inorganic analytes has also been proposed (Table 3). Some works have explored the
369
use of magnetic DES or NADES as extracting solvents with the purpose to simplify the
370
process and improve yields. In general, UAME involves lower volumes of DES (less
371
than 500 µL) and shorter times of extraction (less than 15 min), than the previous
372
mentioned LPME techniques. Like LPME, UAME also did not allow automation of the
373
extraction process.
374
Cvjetko Bubalo et al. [42] used a ChCl-based DES containing oxalic acid as a
375
hydrogen bond donor with 25% of water, for the extraction of grape skin phenolic
376
compounds. To increase extraction yield, samples were sonicated in a water bath
377
during 50 min at 65 °C. According to the authors, t he extraction efficiency obtained by
378
UAME was higher than those obtained with microwave-assisted extraction or
379
conventional extraction methods.
380
Recently, Zhuang et al. [43] combined DES-UAME with HPLC-UV for the simultaneous
381
determination of flavonoid glycosides and respective aglycones in Platycladi Cacumen.
382
In the optimized conditions, 1 ml of DES (ChCl- laevulinic acid with 75% of water) was
383
mixed with 25 mg of sample during 30 min at 50°C un der an ultrasound bath (200 W,
384
40 kHz); the extract was further diluted 8 times with acetonitrile before HPLC-UV
385
analysis. Additionally, the authors evaluated the possibility to recover the target
386
analytes from the DES extracts, in order to enable their further application in
387
pharmaceutical or food industry. For that purpose, several macroporous resins were
388
evaluated, being the best results for both flavonoid glycosides and aglycones obtained
389
with LX-38.
390
Khezeli et al. [44] have reported a simple and highly reproducible UAME method for the
391
determination of ferulic, caffeic and cinnamic acids in olive, almond, sesame, and
392
cinnamon oil samples, using ChCl and ethylene glycol (1:2, molar ratio) as DES
393
extracting solvent. The solvent was added to the sample dissolved in n-hexane, then
394
the mixture was placed in an ultrasound bath for 5 min, to form an emulsion of
395
microdroplets, and consequently increase the contact surface between DES and
396
sample. Once completed the extraction, the DES phase containing the analytes was
397
separated by centrifugation, and submitted to HPLC-UV analysis. The results indicated
398
that the novel approach have shown the advantages of good sensitivity (limits of
399
detection between 0.39 and 0.63 µg/L), reproducibility (RSD <5.1%), convenience
400
(extraction time less than 15 min), and high accuracy (recoveries from 95-105%). Tan
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ACCEPTED MANUSCRIPT 401
et al. [45] employed also UAME-DES followed by HPLC/UV for determination of plant
402
growth
403
tetramethylammonium chloride–ethylene glycol mixture (1:3 molar ratio). When
404
compared with other techniques such as SDME, SPME and S-SIL-based MSPD the
405
UAME-DES proposed in the works above referred are more sensible, fast and simple
406
of execution [39, 40].
407
The applicability of hydrophobic DES for extraction of analytes dissolved in raw waters
408
such as UV-filters have been evaluated by Wang et al [46]. After optimization of diverse
409
parameters (for examples sample volume, salt addition, sample pH, ultrasonic time) the
410
authors proposed the use of a mixture of trioctylmethylammonium chloride with
411
decanoic acid (1:3 molar ratio) as DES, using sonication for 5 min in an ultrasonic bath
412
(150 W; 40 kHz) for pre-concentration and separation of three benzophenones. This
413
method has the great advantage of enabling the extraction and purification in one step
414
without the use of toxic solvents.
415
The use of a magnetic deep eutectic solvent (MDES) formed by the mixture of ChCl
416
with phenol and anhydrous FeCl3 (1:2:1 molar ratio) was recently proposed by Khezeli
417
et al. [47] for the extraction of thiophene from a heptane solution. The MDES was
418
dispersed into the solution by ultrasounds during 5 min, in order to enhance the mass
419
transfer of thiophene from n-heptane to MDES phase. After that, microdroplets of
420
MDES were collected by a magnet and the remained concentration of thiophene in n-
421
heptane was analyzed by GC-FID. The method provided very good results in the
422
elimination of thiophene from the initial solution (close to 100%), with the great
423
advantage of eliminating the centrifugation step usually required in any LPME
424
extraction. According to the authors, the developed MDES are able to be reused after
425
four runs without losses of extraction efficiency.
426
A novel UAME application based on DES, named by the authors as emulsification
427
liquid-liquid microextraction (ELLME-DES) was introduced by the group of Khezeli [48]
428
for the simultaneous extraction of BTE (benzene, toluene, and ethylbenzene) and
429
seven polycyclic aromatic hydrocarbons from water samples. Here, the ultrasound
430
helps both the mass transfer between phases and the formation of tiny emulsified
431
droplets, increasing the contact area. Other novelty was the use of a water miscible
432
aprotic solvent, THF for instance, able to decrease the tendency of water molecules to
433
interact with DES and thus promoting the self-aggregation of DES microdroplets.
434
Briefly, 100 µL of DES (mixture of ChCl:phenol in 1:2, 1:3, and 1:4 molar ratios) were
435
added to 1.5 mL of sample and a homogeneous solution was formed immediately. The
from
several
vegetable
oil
samples,
using
as
DES
a
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15
ACCEPTED MANUSCRIPT further injection of 100 µL of THF followed by sonication for 20 min in an ultrasonic bath
437
provided a turbid state in which DES microdroplets are entirely disperse along all the
438
water phase, so enhancing the transference rate of the compounds from the water to
439
the DES phase. After a centrifugation step (10 min at 3000 rpm) the DES upper phase
440
was withdrawn through a micro-syringe and analyzed by HPLC/UV. Very good results
441
were obtained in what concerns linearity, precision, and accuracy. These approach
442
could be very useful for the multi-analysis of hydrocarbons in environmental water
443
samples, with the advantages of simplicity, low cost, and high sensitivity providing by
444
the high enrichment factor of the extraction procedure, while avoiding the use of
445
chlorinated solvents.
446
Similar approach was used by Aydin et al. [49] for the extraction of malachite green
447
from farmed and ornamental aquarium fish water samples followed by a simple UV–
448
VIS spectrometry analysis. The developed method presented good extraction
449
recoveries (≥95%) and high precision (RSD < 4% for real samples) for evaluation of
450
this anti-parasite which its illegally used in the aquaculture industry to prevent fish
451
diseases caused by external parasites and fungus. Moreover, the method showed a
452
good selectivity for malachite green along with other advantages such as simplicity, low
453
cost, rapid separation and ease of operation. The same authors proposed a ELLME-
454
DES combined vortex for separation and pre-concentration of curcumin in herbal tea
455
samples followed by UV-Vis determination using 400 µL of DES (ChCl: phenol, molar
456
ratio 1:4) as extracting solvent, 400 µL of THF as emulsifier agent and 2 min of
457
ultrasonication to achieve the best extraction[50].
458
The same principles were at the base of the application of DES as extracting solvent
459
on UAME procedures for extraction of inorganic compounds, namely cobalt (II) and
460
chromium (III/VI) ions from aqueous matrices, performed by the group of Soylak [51]
461
[52]. In both works, the metals were previously complexed by adding as ligands 1-
462
nitroso-2-naphthol and sodium diethyldithiocarbamate, respectively, allowing the
463
formation of very stable and hydrophobic complex and consequently promoting the
464
extraction efficiency. The DES solvents were mixtures of ChCl with phenol (4:1, and
465
3:1 molar ratios, respectively) and THF was added to allow the self-aggregation and full
466
separation of the DES molecules from the water phase. Following sonication for 2 min
467
and centrifugation, the authors were able to recollect a DES aggregate containing the
468
complexed metals, suitable for quantification by AAS. Several parameters affecting the
469
extraction performance of the analytes were optimized, namely sample amount, pH,
470
type and volume of DES, of complexing agent, and of emulsifier solvent, and
471
ultrasonication time. The results obtained under the optimized conditions are
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473
from presenting a high enrichment factor and consequently low detection limits.
474
A comparable approach to those previously described was used by Panhwar et al. in
475
two works aiming the pre-concentration of inorganic compounds from water and food
476
samples, namely hydrophobic chelates of Se(IV) with 3,3′-diaminobenzidine [53] and Al
477
(III) with 8-hydroxyquinoline [54] before ETAAS analysis. In both works mixtures of
478
ChCl:phenol were used as extractors with a molar ratio of 1:3 and 1:4, respectively,
479
and THF was the emulsifier agent. The authors compared the proposed methods with
480
other ETAAS procedures previously used, in which the pre-concentration was done
481
with LLE, SPE or conventional DLLME, and found no significant differences between
482
the performance data achieved, with the advantages already indicated that
483
characterize the use of DES.
484
The use of NADES in UAME is been increasing in last years as mentioned for other
485
microextraction techniques. Lores et al. [55] used a fructose-citric acid NADES mixture
486
in combination with UAE for fast and green gluten determination by ELISA. The
487
NADES-UAME developed allows the replacement of the ethanol-water solution
488
commonly used for gluten extraction with success, once good recoveries (62–135%)
489
and high precision RSD < 15%) were obtained. In another work, Bajkacz and Adamek
490
[56] used NADES combined with UAME for the isolation of isoflavones (daidzin,
491
genistin, genistein, daidzein) from soy products followed by UPLC-UV analysis. The
492
best results were obtained using a mixture of ChCl:citric acid (1:1 molar ratio) with a
493
water content of 30%, and a ratio of NADES volume to sample amount of 3 The
494
extraction time was 60 min at 60ºC and the ultrasonic power was 616 W. Bosiljkov et
495
al. [57] used chemometric tools, namely a response surface methodology to optimize
496
NADES-UAME/HPLC-DAD method for the quantification of anthocyanins in wine lees.
497
The maximum amount of extracted compounds were achieved using ChCl:malic acid
498
(1:1 molar ratio) with 35.4% (w/w) of water in a ultrasound bath at 341.5 W during 30.6
499
min. Recently, Huang et al [58] used a NADES-UAME/HPLC-UV method for the
500
extraction of rutin from from tartary buckwheat hull. The authors proved that the
501
solubility of rutin increased by 660–1577 times in ChCL-glycerol-based NADES when
502
compared to water.
503
The increasing number of works using DES and NADES in UAME, in recent years
504
make us believe that this novel class of extracting solvents can be used in removal and
505
extraction of a wide range of analyte in environmental and food matrices. Despite all
506
the advantages, the majority of the DES extracting solvents used in UAME described
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procedures requires the use of HPLC for organic compounds, or ETAAS and AAS for
508
inorganic compounds, as quantitative final technique, due to the incompatibility with GC
509
systems due to DES low volatility.
510
6. MICROWAVE-ASSISTED EXTRACTION
512
MAE employs non-ionized electromagnetic irradiation (in a frequency range of 0.3-300
513
GHz) to heat both solvent and samples by movements of ions and rotation of molecular
514
and atomic dipoles, in order to increase extraction kinetics [59].
515
MAE may be performed in closed vessels under pressure (pressurized MAE) or in
516
open vessels at atmospheric pressure (focused MAE). The first ones are most used in
517
food analysis since usually provide enhanced extraction yields. The extraction
518
efficiency is dependent on the solvent (nature and solvent/sample ratio), temperature
519
and pressure, extraction time, radiation power, sample composition (moisture mainly),
520
and particle size (preferably 0.1 – 2 mm)[41, 59].
521
MAE using DES as extracting solvent was employed by Chen et al. [60] to extract 5
522
active ingredients namely rosmarinic acid, lithospermic acid, salvionalic acid B,
523
salvionalic acid A, and tanshinone II A from Radix Salviae miltiorrhizae followed by
524
HPLC-VWD quantification. Among twenty-five DES tested, the authors concluded that
525
ChCl-1,2-propanediol (1:1, molar ratio) showed the best yields. Other extraction
526
factors, including temperature, time, power of microwave, and solid/liquid ratio, were
527
systematically investigated by response surface methodology. The hydrophilic and
528
hydrophobic compounds were extracted simultaneously under the optimized
529
conditions: 20 vol% of water in ChCl-1,2-propanediol as solvent, microwave power of
530
800 W, temperature at 70°C, time at 11.11 min, and solid/liquid ratio of 0.007 g/ml. The
531
proposed DES combined with the MAE provided a prominent advantage for fast and
532
efficient extraction of active compounds compared with conventional procedures.
533
Moreover, in comparison to the techniques previously used, MAE allows the
534
automation of the extraction (40 samples per batch). The main limitations of MAE
535
based techniques are the higher costs of the equipment and the usual presence on the
536
extracts of many interfering compounds due to the exhaustive extraction process,
537
which requires a cleanup step prior to the analysis.
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7. OTHER APPLICATIONS OF DES/NADES IN EXTRACTION TECHNIQUES
18
ACCEPTED MANUSCRIPT 540
DES have been also demonstrated to be an interesting alternative as reaction solvents
541
in the production of new sorbents [61] or polymeric phases [62] used in solid-phase
542
extractions (SPE), which enhance the range of possible DES applications in
543
environmentally friendly extraction procedures. Another application is using DES as
544
dissolution solvent [63] as a new alternative to the conventional Soxhlet extraction.
545 7.1. DES as solvents on liquid-liquid extraction
547
Guo et al. [64] used a DES based on tetrahylammonium chloride and phenol (0.8:1,
548
molar ratio) to extract phenol (99.9%) from model oil (toluene). The extraction was
549
achieved by mixing directly the DES with the matrix by 30 min at room temperature,
550
avoiding the use of alkali and acids and the production of phenol containing waste
551
water, common in the traditional methods. The same group previously has verified that
552
the addition of ChCl allowed a formation of DES due to the presence of phenols
553
(phenol, cresols) in model oils (hexane, toluene, and p-xylene) [65]. The extraction of
554
phenolic compounds from virgin olive oil using DES as extracting solvent was
555
evaluated by García et al. [66]. The best results for the two most abundant secoiridoid
556
derivatives (oleacein and oleocanthal) were obtained with ChCl: xylitol (2:1, molar ratio)
557
and chlorine chloride:1,2 propanediol (1:1, molar ratio) as DES solvents. The better
558
conditions were achieved by mixing the extractive solvent directly with the samples
559
inside a bath at 40°C with agitation for 1 h. Excel lent extraction yields were obtained
560
with the tested DES compared with the commonly used mixture of methanol/water.
561
Despite all the advantages due to the use of DES such as low cost and low toxicity, the
562
extraction time was not reduced.
563
The group of Ghanemi [67] for determination of PAHs by HPLC-UV used DES (ChCl–
564
Ox, 1:2 molar ratio) at 55°C for 30 min to dissolve fish samples. After dissolution, PAHs
565
were quantitatively extracted from ChCl-Ox solution with 5 ml of cyclohexane and
566
stirring for 20 min [67]. These procedures provide some operational advantages when
567
compared with the conventional Soxhlet extraction such as simplicity, low-cost and
568
eco-sustainability of the eutectic solvent, relatively high-speed sample preparation and
569
low consumption of both sample and organic solvents. Similar advantages were also
570
described by Bi et al. [68] who applied a mixture of ChCl and 1,4-butanediol (1:5 molar
571
ratio) with 35% of water at 70°C for 40 min for the extraction of antioxidant flavonoids
572
(myricetin and mentoflavone) from leave plants, using a sample/volume ratio of 1 g/10
573
ml.
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7.2. DES as sorbent on solid-phase extraction 19
ACCEPTED MANUSCRIPT Solid-phase extraction (SPE) is one of the most popular extraction techniques, making
577
use of a wide range of supporting packings commercially available with different
578
sorbents. Depending on the nature of the sorbent, a number of mechanisms of solute
579
retention can be assumed to rule the process. Partitioning of analytes between a liquid
580
solution (sample matrix or extract) and a viscous liquid that is immobilized on a solid
581
support (sorbent phase) is the most usual retention mechanism for SPE process.
582
Liquid/solid adsorption as well as ion exchange or size exclusion are also possible
583
mechanisms in various separations [69]. SPE extraction is a safe, efficient and
584
reproducible separation technique that can be automatized.
585
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Wang et al. [61] employed DES (ChCl and urea, 1:2 molar ratio) as reaction solvent to
587
prepare a new nitro-substituted tris(indolyl)methane modified silica phase. This new
588
sorbent was used in the extraction of organic acids (benzoic, p-anisic, salicylic and
589
cinnamic acids) from grape juice and mineralized drinking water followed by HPLC-
590
DAD analysis. Owing the multiple intermolecular forces of the new phase, such as π–
591
π, hydrogen bonding and hydrophobic interactions, good extraction efficiency
592
(recoveries >68%) was achieved for the selected organic acids. Another important
593
advantage of this SPE sorbent is the possibility to be reused, which decrease the cost
594
of the analysis.
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Liu et al. [70] used a DES (ChCl: ethylene glycol) to modify graphene. Compared with
597
conventional graphene, DES-graphene had a large winkle and formed a structure with
598
a high specific surface area because linked groups were introduced into the parent
599
graphene structure what give it a higher adsorption ability. Two milligrams of DES-
600
graphene were employed to pipette-tip SPE of sulfamerazine from river waters followed
601
by HPLC analysis. The optimization of PT-SPE included the evaluation of volume of
602
washing and elution solvent. Under the optimum conditions this method showed good
603
recoveries (91-97%) and higher precision intraday (RSD range from 1.6 to 3.5%) and
604
interday (RSD range from 0.7-3.8%).
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7.3. DES as dissolution solvent
607
DES have been used by the group of Ghanemi [63] for the dissolution of marine
608
biological samples, which facilitated the quantitative extraction of some metals under
609
study with small volumes of dilute nitric acid for determination by FAAS. Briefly, in this
610
method, 100 mg of the sample were dissolved in ChCl–Ox (1:2, molar ratio) at 100 °C
611
for 45 min. Then, after addition of 5.0 mL HNO3 (1.0 M) the mixture was centrifuged 20
ACCEPTED MANUSCRIPT 612
and the supernatant analyzed. This procedure provided some clear advantage when
613
compared with other techniques (microwave or ultrasonic acid digestion) such as low-
614
cost and simplicity of the sample preparation while avoiding the formation of highly
615
carcinogenic nitrous vapors.
616 7.4. DES as carbon paste electrode
618
Carbon paste prepared through a mixture of carbon (graphite) powder and a binder
619
(pasting liquid), has been used in the preparation of various electrodes, sensors, and
620
detectors [65]. Currently, CPEs represent a popular type of electrode, because carbon
621
pastes are easily obtainable at minimal costs and can be modified simply to obtain
622
quantitatively new sensors with the desired properties. The basic requirements for a
623
pasting liquid are its practical insolubility in the solution under measurement, a low
624
vapour pressure to ensure both mechanical stability and long lifetime, and further, in
625
the case of voltammetric and amperometric applications, its electrochemical inactivity
626
in the potential window of interest [71].
627
Zhu et al. [62] used a NADES composed of ChCl and urea (2:1 molar ratio) mixed with
628
graphite power to prepare a CPE, which was used to directly extract DEHP from
629
polymer films. The microextraction process follows an exponential association function
630
with the apparent first order rate constant of 6.35×10-4 s-1.
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631
7.5. DES as modified molecular imprinted polymers (MIP)
633
MIPs are crosslinked polymers containing specific recognition sites (involved in various
634
types of interactions- covalent, non-covalent and semi-covalent) with a predetermined
635
selectivity for a target analyte. This technique provides several advantages, such as
636
high selectivity and great stability to heating and pH shifts when compared with SPE
637
and LLE. MIPs have been commonly employed in the preconcentration of analytes,
638
acting as the selective adsorbent of SPE [72]. However, MIP’s preparation can pose
639
some problems, like inconsistent molecular recognition, polymer swelling in
640
unfavorable solvents, slow binding kinetics, and potential sample contamination by
641
template bleeding [72].
642
Li et al. [73] compared the efficiency of a DES (synthesized with ChCl and glycerol, 1:2
643
molar ratio) modified molecular imprinted polymer a DES modified non-imprinted
644
polymers (without template), a MIP (without DES) and a NIP (without DES and without
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ACCEPTED MANUSCRIPT template) for the purification of chlorogenic acid from honeysuckles. The extract of
646
honeysuckles was previous obtained using ultrasound (20 min), ethanol at 60% and a
647
ratio of liquid to material (15 ml/g). Among the polymers proposed the DES-MIPs used
648
as SPE showed the highest adsorption capacity owing to its specific imprinted
649
recognition and the DES improved affinity, selectivity and adsorption in purification.
650
A similar approach was applied by the same group more recently using DES formed by
651
ChCl and glycerol (1:2 molar ratio) to synthetize a novel MIP/SPE. The application was
652
successfully applied in the purification of chloromycetin and thiamphenicol from milk
653
[74].
654
8.
655
MICROEXTRACTION TECHNIQUES
656
A broad range of analytical extractive and microextractive techniques have been
657
developed using DES/NADES as extracting solvents for many quantitative analytical
658
purposes such as ETAAS determination of inorganic compounds, and HPLC and GC
659
determination of organic compounds. In the majority of the cases, when DES/NADES
660
are employed as extracting solvent in various DLLME, UAME, MAE and other
661
microextractions procedures, HPLC is preferred to GC as final quantitative technique
662
since the low volatility of the DES/NADES hinder the GC analysis. Nevertheless, Tang
663
et al. [28], Farajzadeh et al. [33], Lamei et al.[34] and Khezeli et al. [47] have
664
successfully employed GC-FID for quantification of several organic compounds using
665
the direct injection of DES extract. The possible contamination of the GC system
666
namely column and injector due to insufficient volatilization of DES extracts was not
667
mentioned in these works. Therefore, the advantages of the use of DES with
668
microextraction techniques, avoiding the toxicity associated with the use of organic
669
solvents, are added to the analytical possibilities of GC. Furthermore, DES as extractor
670
possess an extensive range of polarity/volatility which can be useful in many pre-
671
concentration and separation processes.
TECHNOLOGIES
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673
9. OUTLOOK OF DES/NADES SOLVENTS WITHIN GREEN ANALYTICAL
674
CHEMISTRY
675
According to the twelve principles that govern the concept of Green Chemistry
676
proposed by Anastas and Warner[1], analytical methods should reduce or eliminate
677
hazardous substances used in or generated by a method. The use of DES/ NADES as 22
ACCEPTED MANUSCRIPT extracting solvents in sample preparation techniques fits perfectly with this approach
679
due to their low toxicity and high biodegradability. Additionally, strategies that combine
680
the use of low volumes of these solvents such as LPME, MAE and UAME with green
681
analytical techniques like thermogravimetric, electrochemical or immunoassays
682
analysis [75, 76] are regarded as very interesting green analytical approaches. Despite
683
most of the described sample preparation methodologies presented in the previous
684
sections can be fully considered as environmental-friendly, especially due to low green
685
solvent consumption, the further use of a chromatographic analytical determination
686
commonly associated increases energy costs of the analysis which is somehow a
687
drawback for the analytical method greenness (Table 3). According the existing green
688
analytical evaluation tools (National Environmental Methods Index and Eco-scale) [75,
689
76] the most energy-consuming techniques are NMR, GC-MS, LC-MS, and X-ray
690
diffractometry as opposed to immunoassay, spectroscopy, and electrochemical
691
techniques that are the more energy saved. Additional penalty points on the scales of
692
assessment of analytical methods greenness comes from the requirements of
693
calibration and validation of the methods, since the use of calibration solutions, internal
694
and external standards, standard reference materials or isotope dilution enhance
695
reagents consumption and waste generation [76]. In summary, ideal green analytical
696
methods will be those that eliminate or minimize the use of hazardous solvents, reduce
697
energy use and generate minute quantities of wastes. Therefore, clear efforts are still
698
needed to be made to encourage the development of sustainable analytical methods
699
based on the use of DES and NADES solvents. Information regarding the performance
700
of (micro)extraction techniques based on application of DES/NADES are highlighted in
701
Table 4.
702
10. CONCLUSIONS AND FUTURE PERSPECTIVES
703
In sample preparation, the choice of the right extracting solvent is essential to achieve
704
a near-complete extraction of the analytes of interest, simultaneously with minimizing
705
the amount of interferents. For this purpose, a new class of alternative and
706
environmental-friendly DES and NADES solvents have been employed in several novel
707
microextraction techniques such as LPME, UAME and MAE as well as in more
708
conventional extraction procedures like SPE. Indeed, by replacing conventional
709
solvents with DES the main merits of microextraction techniques such as simplicity of
710
operation, low cost, and environmental safety were enhanced. Additionally, the
711
selective and sensitive achieved by the new analytical methods designed for food and
712
environmental analysis was often better than those obtained by conventional extraction
713
techniques.
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ACCEPTED MANUSCRIPT There is no doubt that the application of DES and NADES solvents in food and
715
environmental analysis will grow in a near future. Forthcoming studies and
716
developments utilizing DES may focus on the following areas; (I) synthesis of new DES
717
and NADES solvents with different polarities and their exploitation in the development
718
of novel extraction techniques for multi-analyte food and environmental analyses; (II)
719
enhancement of the performance and selectivity of the several microextraction
720
techniques to help the execution of the extraction and separation procedure in the
721
analytical laboratories; and (III) employment of new DES and NADES as extracting
722
solvents, sorbents or selective binding agents for the trace analysis of contaminants in
723
both food and environmental samples.
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ACCEPTED MANUSCRIPT 725
ACKNOWLEDGMENTS
726 727 728 729 730
Sara C. Cunha and José Fernandes thanks REQUIMTE, FCT (Fundação para a Ciência e a Tecnologia) and FEDER through the project UID/QUI/50006/2013 – POCI/01/0145/FEDER/007265 with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020. Sara C. Cunha acknowledges FCT for the IF/01616/2015 contract.
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731 References
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ACCEPTED MANUSCRIPT [49] F. Aydin, E. Yilmaz, M. Soylak, A simple and novel deep eutectic solvent based ultrasoundassisted emulsification liquid phase microextraction method for malachite green in farmed and ornamental aquarium fish water samples, Microchemical Journal, 132 (2017) 280-285. [50] F. Aydin, E. Yilmaz, M. Soylak, Vortex assisted deep eutectic solvent (DES)-emulsification liquid-liquid microextraction of trace curcumin in food and herbal tea samples, Food Chem, 243 (2018) 442-447. [51] M.B. Arain, E. Yilmaz, M. Soylak, Deep eutectic solvent based ultrasonic assisted liquid phase microextraction for the FAAS determination of cobalt, Journal of Molecular Liquids, 224 (2016) 538-543. [52] E. Yilmaz, M. Soylak, Ultrasound assisted-deep eutectic solvent based on emulsification liquid phase microextraction combined with microsample injection flame atomic absorption spectrometry for valence speciation of chromium(III/VI) in environmental samples, Talanta, 160 (2016) 680-685. [53] A.H. Panhwar, M. Tuzen, T.G. Kazi, Ultrasonic assisted dispersive liquid-liquid microextraction method based on deep eutectic solvent for speciation, preconcentration and determination of selenium species (IV) and (VI) in water and food samples, Talanta, 175 (2017) 352-358. [54] A.H. Panhwar, M. Tuzen, T.G. Kazi, Deep eutectic solvent based advance microextraction method for determination of aluminum in water and food samples: Multivariate study, Talanta, 178 (2018) 588-593. [55] H. Lores, V. Romero, I. Costas, C. Bendicho, I. Lavilla, Natural deep eutectic solvents in combination with ultrasonic energy as a green approach for solubilisation of proteins: application to gluten determination by immunoassay, Talanta, 162 (2017) 453-459. [56] S. Bajkacz, J. Adamek, Evaluation of new natural deep eutectic solvents for the extraction of isoflavones from soy products, Talanta, 168 (2017) 329-335. [57] T. Bosiljkov, F. Dujmić, M. Cvjetko Bubalo, J. Hribar, R. Vidrih, M. Brnčić, E. Zlatic, I. Radojčić Redovniković, S. Jokić, Natural deep eutectic solvents and ultrasound-assisted extraction: Green approaches for extraction of wine lees anthocyanins, Food and Bioproducts Processing, 102 (2017) 195-203. [58] Y. Huang, F. Feng, J. Jiang, Y. Qiao, T. Wu, J. Voglmeir, Z.-G. Chen, Green and efficient extraction of rutin from tartary buckwheat hull by using natural deep eutectic solvents, Food Chemistry, 221 (2017) 1400-1405. [59] S. Moldoveanu, V. David, Chapter 7 - Solid-Phase Extraction, Modern Sample Preparation for Chromatography, Elsevier, Amsterdam, 2015, pp. 191-286. [60] J. Chen, M. Liu, Q. Wang, H. Du, L. Zhang, Deep Eutectic Solvent-Based MicrowaveAssisted Method for Extraction of Hydrophilic and Hydrophobic Components from Radix Salviae miltiorrhizae, Molecules, 21 (2016). [61] N. Wang, J. Wang, Y. Liao, S. Shao, Preparation of a nitro-substituted tris(indolyl)methane modified silica in deep eutectic solvents for solid-phase extraction of organic acids, Talanta, 151 (2016) 1-7. [62] J.G. X. Zhu, J. Lang, H. Zhang, Y. Zhu, Liquid phase microextarion of Di2 ethylexyl phthalate, International Journal of Innovative Research in Science, Engineering and Technology
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ACCEPTED MANUSCRIPT [65] I. Švancara, K. Vytřas, K. Kalcher, A. Walcarius, J. Wang, Carbon Paste Electrodes in Facts, Numbers, and Notes: A Review on the Occasion of the 50-Years Jubilee of Carbon Paste in Electrochemistry and Electroanalysis, Electroanalysis, 21 (2009) 7-28. [66] A. García, E. Rodríguez-Juan, G. Rodríguez-Gutiérrez, J.J. Rios, J. Fernández-Bolaños, Extraction of phenolic compounds from virgin olive oil by deep eutectic solvents (DESs), Food Chemistry, 197, Part A (2016) 554-561. [67] Z. Helalat-Nezhad, K. Ghanemi, M. Fallah-Mehrjardi, Dissolution of biological samples in deep eutectic solvents: an approach for extraction of polycyclic aromatic hydrocarbons followed by liquid chromatography-fluorescence detection, J Chromatogr A, 1394 (2015) 4653. [68] W. Bi, M. Tian, K.H. Row, Evaluation of alcohol-based deep eutectic solvent in extraction and determination of flavonoids with response surface methodology optimization, J Chromatogr A, 1285 (2013) 22-30. [69] S.M.a.V. David, Modern Sample Preparation for Chromatography, in: S.D. Moldoveanu, V. (Ed.), 2015, pp. 33-51. [70] L. Liu, W. Tang, B. Tang, D. Han, K.H. Row, T. Zhu, Pipette-tip solid-phase extraction based on deep eutectic solvent modified graphene for the determination of sulfamerazine in river water, J Sep Sci, 40 (2017) 1887-1895. [71] K. Vytřas, I. Svancara, R. Metelka, Carbon paste electrodes in electroanalytical chemistry, Journal of the Serbian Chemical Society, 74 (2009) 1021-1033. [72] V.L. Pereira, J.O. Fernandes, S.C. Cunha, Mycotoxins in cereals and related foodstuffs: A review on occurrence and recent methods of analysis, Trends in Food Science & Technology, 36 (2014) 96-136. [73] G. Li, W. Wang, Q. Wang, T. Zhu, Deep Eutectic Solvents Modified Molecular Imprinted Polymers for Optimized Purification of Chlorogenic Acid from Honeysuckle, J Chromatogr Sci, 54 (2016) 271-279. [74] G. Li, T. Zhu, K.H. Row, Deep eutectic solvents for the purification of chloromycetin and thiamphenicol from milk, J Sep Sci, 40 (2017) 625-634. [75] L.U.G. L. H. Keith, J.L.Young, Green Analytical Methodologies, Chem Rev, 107 (2007) 26952708. [76] A. Gałuszka, Z.M. Migaszewski, P. Konieczka, J. Namieśnik, Analytical Eco-Scale for assessing the greenness of analytical procedures, TrAC Trends in Analytical Chemistry, 37 (2012) 61-72.
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Figure Capitations
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Figure 1- Time-trend (2006-2017) representation of the DES and NADES application and their distribution in the different Web Science Categories.
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ACCEPTED MANUSCRIPT Table 1- Density, viscosity, condutivity and spectroscopic polarity index (ETN)of some DES at specific temperatures [3-5,16]
DES (molar ratio)
Density
Viscosity
Condutivity
ET N
Urea:ChCl (2:1)
g/cm 1.25 (25°C)
mm /s 750 (25°C)
(mS cm-1) 0.20 (40°C)
0.84
Ethylene Glycol: ChCl (2:1)
1.12 (25°C)
37 (25°C)
7.61 (20°C)
0.8
Glycerol: ChCl (2:1)
1.18 (25°C)
359 (25°C)
1.05 (20°C )
0.86
Malonic: ChCl (1:1)
1.25 (25°C)
721 (25°C)
1,4- butanediol: ChCl (3:1)
1.06
140 (20°C)
Urea: ethylammonium chloride (1.5:1)
1.041
128 (40 °C )
Acetamide: ethylammonium chloride (1.5:1)
1.14
64 (40 °C)
2,2,2-trifluoroacetamide: ChCl (2:1)
1.342
77 (40 °C)
Water
0.992
1
RI PT
2
0.55 (25°C)
-
1.64 (20°C )
-
-
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-
0.69 (40 °C)
-
0.286 (40 °C)
-
250
1
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ACCEPTED MANUSCRIPT Table 2- Density, viscosity, decomposition temperature (Td) and glass transition temperature (Tg) of some NADES at specific temperatures [4,20]
NADES (molar ratio)
Density (40°C) 3
Viscosity (40°C)
T d/°C
T g/°C
2
mm /s
Fructose: ChCl: water (2:5:5)
1.2078
280.8
160
-84.58
Glucose: ChCl: water (2:5:5)
1.2069
397.4
170
-83.86
Lactic acid: glucose:water (5:1:3)
1.2497
37
135
-77.06
1.14
226.8
176.6
-11.9
Malic acid: ChCl: water (1:1:2)
1.2303
445.9
201
-71.32
Sorbitol: ChCl: water (2:5:6)
1.1854
138.4
>200
-89.62
Sucrose: ChCl: water (1:4:4)
1.2269
581
>200
-82.96
Xylitol: ChCl: water (1:2:3)
1.17841
86.1
>200
-93.33
Water
0.992
SC
Levulinic acid: ChCl (2:1)
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g/cm
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ACCEPTED MANUSCRIPT
Techniques LPME LPME
Sample DES - NADES Composition Molar ratio Volume Type ChCl -1,4-butanediol 1:5 2.0 ml Leaves (Chamaecyparis obtusa) ChCl -xylitol 2:1 14 g Olive oil
Extraction amount 200 mg
Time 40 min
14 g
1h
ChCl-urea
1:2
50 µl
Water samples (farm water, rural water, lake water and river water)
50 ml
1 min
AG-DLLME
ChCl-4-Chlorophenol
1:2
190 µl
Fruit and vegetable juice
5 ml
6 min
AAELLME
ChCl-5,6,7,8-Tetrahydro-5,5,8,8tetramethylnaphthalen-2-ol
1:2
100 µl
Water, urine and plasma
Urine added with NaOH solution (2 mol/l) until pH 10 and dilluted to 10 ml with water. The supernatant of 1 ml plasma with 0.5 ml zinc sulfate solution (0.7 mol/l) and 0.1 ml sodium hydroxide solution (1 mol/l) was dilluted to 10 ml with water
HPLME
ChCl-ethylene glycol
1:3
10 µl
HPLME
ChCl-ethylene glycol
1:4
2 µl
Gasoline, diesel fuel, kerosene Leaves of Chamaecyparis obtusa
LPME
Lactic acid–glucose-water
5:1:3
1.5 ml
LPME
Sucrose-ChCl:water
1:4:4
1.5 ml
LPME
Sucrose-ChCl:water
1:4:4
3 ml
Other features
Analyts extracted
Instrumental analysis
Heating 70°C- 30% vol water Heating 40 °C
Flavonoids (myricetin, amentoflavone)
HPLC-UV
Phenolic compounds (hydroxytyrosol, tyrosol, oleacein, oleocanthal, oleuropein agylcon,ligstroside aglycon) 5 mg MMWCNTs, 150 ml Pesticides (alpha-HCH, beta-HCH, acetonitrile, ultrasonic bath gamma-HCH, delta-HCH, heptachlor, aldrin, heptachlor-endo-epoxide, alphaendosulfan, dieldrin, 4,4′ –DDE, endrin, betaendosulfan, 4,4′ –DDD, endrinaldehyde, endosulfan-sulfate, 4,4′ –DDT, endrin-ketone and methoxychlor)
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pH 2; water bath at 40°C for Pesticides (Penconazole, hexaconazole, 3 min, ice and NaCl bath diniconazole, tebuconazole, diazinon, fenazaquin, clodinafoppropargyl, and haloxyfopR-methyl)
LOD Myricetin-0.07 µg/ml; amentoflavone-0.09 µg/ml
Ref. 68 66
GC-ECD
alpha-HCB 0.83 ng/l; beta-HCH 0.20 ng/l; gamma-HCH 0.50 ng/l; delta-HCB-0.17 ng/l; heptachlor0.89 ng/l; aldrin 0.73 ng/l; heptachlor endoepoxide 0.46 ng/l; alpha-endosulfan 0.13 ng/l; dieldrin- 0.10 ng/l; 4,4′ -DDE0.17 ng/l; endrin- 0.17 ng/l; betaendosulfan 0.17 ng/l; 4,4′ -DDD0.17 ng/l; endrin-aldehyde 0.36 ng/l; endosulfan-sulfate 0.43 ng/l; 4,4′ -DDT- 0.73 ng/l; endrinketone- 0.63 ng/l; methoxychlor0.36 ng/l
alpha-HCH 0.25 ng/l; beta-HCH 0.06 ng/l; gamma-HCH 0.15 ng/l; delta-HCH- 0.05 ng/l; heptachlor0.27 ng/l; aldrin- 0.22 ng/l; heptachlor endoepoxide 0.14 ng/l; alpha-endosulfan- 0.04 ng/l; dieldrin- 0.03 ng/l; 4,4′ -DDE 0.05 ng/l; endrin- 0.05 ng/l; betaendosulfan 0.05 ng/l; 4,4′ -DDD 0.05 ng/l; endrin-aldehyde 0.11 ng/l; endosulfan-sulfate 0.13 ng/l; 4,4′ -DDT- 0.22 ng/l; endrinketone- 0.19 ng/l; methoxychlor0.11 ng/l
31
GC-FID
Diazinon 4.2 µg/l; penconazole Diazinon 1.4 µg/l; penconazole 0.75 µg/l; haloxyfop-R-methyl 1.4 0.25 µg/l; haloxyfop-R-methyl µg/l; hexaconazole 0.84 µg/l; 0.45 µg/l; hexaconazole 0.28 µg/l; diniconazole 1.3 µg/l; clodinafop- diniconazole 0.43 µg/l; clodinafoppropargyl 3.9 µg/l; tebuconazole propargyl 1.3 µg/l; tebuconazole 0.64 µg/l; bromopropylate 0.24 1.9 µg/l; bromopropylate 0.71 µg/l; fenazaquin 2.7 µg/l µg/l; fenazaquin 0.90 µg/l
33
pH 10; 100 µl THF; 10 times pulling and pushing
Methadone
GC-FID
0.70 µg/l
2.30 µg/l
34
AC C
EP
3 min
LOQ
HPLC-DAD
SC
DLLME
RI PT
Table 3- Summary of the application of DES and NADES in extraction techniques from 2006-2017
Orange petals of Catharanthus roseus Safflower (Carthamus tinctorius L. ) Safflower (Carthamus tinctorius L. )
1 ml
3 min
Ultrasonic bath
Phenolic (phenol, ρ -cresol, β-naphthol)
HPLC-UV
300 mg
30 min
Heating 100 °C ultrasonic irradion 70W
Bioactive terpenoids (Linalool, αterpineol, terpinyl-acetate)
GC-FID
phenol-0.025 µg/l; ρ -cresol-0.05 µg/l; β-naphthol Linalool- 6.687 ng/ml; α-terpineol- Linalool- 2.006 ng/ml; α-terpineol10.50 ng/ml; terpinylacetate3.150 ng/ml; terpinylacetate7.099 ng/ml 2.129 ng/ml
29 28
50 mg
30 min
Stirring at 40 °C
Anthocyanins
UPLC-TOF- M S
39
100 mg
1h
Stirring at 40 °C
HPLC-DAD
37
50 mg
30 min
Stirring at 40 °C
Phenolic compounds (hydro xysafflor Yellow A, cartormin, and carthamin) Colorants (carthamin)
H PLC-DAD
38
ACCEPTED MANUSCRIPT
UAME
DES - NADES Composition Molar ratio Volume ChCl-ethylene glycol 1:2 50 µl
Extraction
Sample Type Olive, almond, sesame and Cinnamon oils
amount 2 ml (1 ml oil -1 ml hexane)
Time 5 min
Other features
Analyts extracted
Instrumental analysis
LOQ
LOD
Ref.
Ultrasonic bath
Phenolic acids (ferulic, caffeic, and cinnamic acids)
HPLC-UV
Ferulic acid -1.30-1.86 µg/l; caffeic acid - 1.43-2.10 µg/l; cinnamic acid 1.60-2.10 µg/l
Ferulic acid -0.39-0.56 µg/l; caffeic acid - 0.43-0.63 µg/l ; cinnamic acid 0.48-0.63 µg/l
44
Cobalt (II)
FAAS
3.60 µg/l
1.1 µg/l
51
FAAS
18.2 µg/l
5.5 µg/l
52
HPLC-UV
Benzene- 21.0 µg/l; toluene- 22.0 µg/l; ethylbenzene-2.90 µg/l; biphenyl- 2.30 µg/l; fluorene- 2.20 µg/l; phenanthrene- 0.30 µg/l; anthracene- 0.06 µg/l; pyrene0.26 µg/l; chrysene- 0.70 µg/l; benzo[a ]pyrene- 0.28 µg/l
Benzene- 6.2 µg/l; toluene- 6.8 µg/l; ethylbenzene-0.8 µg/l; biphenyl- 0.7 µg/l; fluorene- 0.7 µg/l; phenanthrene- 0.09 µg/l; anthracene- 0.02 µg/l; pyrene0.07 µg/l; chrysene- 0.21 µg/l; benzo[a ]pyrene- 0.08 µg/l
48
RI PT
Techniques
ChCl-phenol
1:4
500 µl
Tea
Residue resulted of wet digestion (0.5 g) added with 10 ml water
2 min
Ultrasonic bath; pH >6; 1 ml nitroso-2-naphthol; 0.5 ml THF
UALME
ChCl-phenol
1:3
450 µl
Waters (tap, lake, waste)
10 ml
2 min
Ultrasonic bath; 0.375 ml Chromium (III/VI) 0.5M H2SO4; 0.4 ml 0.125% sodium diethyldithiocarbamate; 0.45 ml THF Ultrasonic bath (35 kHz) Thiophene 25°C Ultrasonic bath; 100 µl THF Benzene, toluene, ethylbenezene, PAHs (biphenyl, fluorene, phenanthrene, anthracene, pyrene, chrysene and benzo[a]pyrene )
SC
UALME
ChCl:phenol:FeCl3
1:2:1
25 µl
n-heptane
1.5 ml
5 min
ChCl-phenol
1:2
100 µl
Waters (tap and industrial wastewater)
1.5 ml
20 min
UALME
ChCl-phenol
1:4
500 µl
2 ml
3 min
Ultrasonic bath; pH =3; 500 µl THF
Malachite green
UV-VIS
11.8 µg/l
3.6 µg/l
49
UALME
ChCl-Ox
1:1
1 ml
Waters (farmed and ornamental aquarium fish) Grape skin
100 mg freeze dried skin
50 min
Ultrasonic bath: 65 °C, 35 kHz; 25% water
Phenolics ((+)-Catechin, delphinindin-3O - glucoside, Cyanidin-3-O- glucoside, petunidin-3-O -glucoside, peonidin-3-O glucoside, malvidin-3-O -glucoside, quercetin-3-O -glucoside)
HPLC-UV
(+)-Catechin- 1.24 mg/l, delphinindin-3-O- glucoside- 0.60 mg/l, Cyanidin-3-O-glucoside0.71 mg/l, petunidin-3-Oglucoside- 0.80 mg/l, peonidin-3O-glucoside-0.65 mg/l, malvidin3-O-glucoside - 0.90 mg/l, quercetin-3-O-glucoside -0.46 mg/l
(+)-Catechin- 0.37 mg/l, delphinindin-3-O- glucoside- 0.18 mg/l, cyanidin-3-O-glucoside-0.21 mg/l, petunidin-3-O-glucoside0.24 mg/l, peonidin-3-O-glucoside0.19 mg/l, malvidin-3-O-glucoside - 0.30 mg/l, quercetin-3-Oglucoside -0.05 mg/l
42
UALME
tetramethylammonium chloride–ethylene glycol
1:3
30 µl
Saflower, olive,camellia, colza and soybean oils
1 ml (10 % oil - 90% hexane)
IAA -0.05 µg/ml; IBA -0.06 µg/ml; 4-IPOAA 0.75 µg/ml
45
UALME
Choline Chloride-Laevulinic Acid
1:2
1 ml
Platycladi Cacumen
25 mg
UAME
Choline chloride-malic acid
1:1
1 ml
Wine lees
33.3 mg
UAME
Choline chloride-glycerol
1:1
1 ml
tartary buckwheat hulls
UAME
Fructose-citric acid
1:1
1 ml
UAME
ChCl:citric acid
1.1
600 µl
Raw and processed food (spaghetti, biscuts, and ham) Soy products (soybeans, flour, pasta, breakfast cereals, cutlets, tripe, soy drink, soy nuts, soy cubes and three different dietary supplements)
MAE
ChCl-1,2-propanediol
1:1
10 ml
TE D
GC-FID
47
Ultrasonic bath -50°C
Plant growth regulators ( IAA, IBA, 4IPOAA)
HPLC-UV
30 min
Ultrasonic bath: 50°C, 200 W; 75% water
Flavonoid glycosides and aglycones (myricitrin, quercitrin, amentoflavone, hinokiflavone) Anthocyanins
HPLC-UV
HPLC-DAD
Flavonoid (rutin)
HPLC-UV
58
Gluten
Enzyme Linked ImmunoSorbent Assay
55
Isoflavones (GT, DA, GTGL, daidzin DAGL)
UHPC-UV
DAGL- 0.40 µg/g; GTGL- 0.45 µg/g; DA- 0.25 µg/g; GT 0.20 µg/g
DAGL- 0.12 µg/g; GTGL- 0.14 µg/g; DA- 0.08 µg/g; GT 0.06 µg/g
56
Bioactive compoun ds (ROS, LIT, SAB, SAA, TIIA)
HPLC-DAD
ROS- 0.80 µg/ml; LIT- 1.37 µg/ml; SAB- 1.96 µg/ml; SAA0.87 µg/ml; TIIA- 1.45 µg/ml
ROS- 0.24 µg/ml; LIT- 0.49 µg/ml; SAB- 0.62 µg/ml; SAA- 0.31 µg/ml; TIIA- 0.48 µg/ml
60
EP
7 min
30.6 min
Ultrasaound bath: 341.5 W, 37 kHz, 35°C ; 35.4% water
40 mg
1h
25 mg
15 min
200 mg
60 min
Ultrasaound bath: 20 kHz, 200 W, 40 °C; 20% water Ultrasound bath (100 w 42 kHz) 40% amplitude; 20% water Ultrasonic bath: 440 W, 60°C; 30% water
50 mg
11.11 min
AC C
Radix Salviae miltiorrhizae
M AN U
UALME UALME
Microwave: 800W, 70°C
43
Delphinidin-3-O glucoside- 0.87 Delphinidin-3-O glucoside- 0.28 mg/l; cyanidin-3-O glucosidemg/l; cyanidin-3-O glucoside0.52 mg/l; petunidin-3-O 0.17 mg/l; petunidin-3-O glucoside- 0.44 mg/l; peonidin-3- glucoside- 0.15 mg/l; peonidin-3O glucoside- 0.62 mg/l; malvidin- O glucoside- 0.2 mg/l; malvidin-33-O glucoside- 0.81 mg/l O glucoside- 0.25 mg/l
57
ACCEPTED MANUSCRIPT
UAME
DES - NADES Composition Molar ratio Volume ChCl-ethylene glycol 1:2 50 µl
Extraction
Sample Type Olive, almond, sesame and Cinnamon oils
amount 2 ml (1 ml oil -1 ml hexane)
Time 5 min
Other features
Analyts extracted
Instrumental analysis
LOQ
LOD
Ref.
Ultrasonic bath
Phenolic acids (ferulic, caffeic, and cinnamic acids)
HPLC-UV
Ferulic acid -1.30-1.86 µg/l; caffeic acid - 1.43-2.10 µg/l; cinnamic acid 1.60-2.10 µg/l
Ferulic acid -0.39-0.56 µg/l; caffeic acid - 0.43-0.63 µg/l ; cinnamic acid 0.48-0.63 µg/l
44
Cobalt (II)
FAAS
3.60 µg/l
1.1 µg/l
51
FAAS
18.2 µg/l
5.5 µg/l
52
HPLC-UV
Benzene- 21.0 µg/l; toluene- 22.0 µg/l; ethylbenzene-2.90 µg/l; biphenyl- 2.30 µg/l; fluorene- 2.20 µg/l; phenanthrene- 0.30 µg/l; anthracene- 0.06 µg/l; pyrene0.26 µg/l; chrysene- 0.70 µg/l; benzo[a ]pyrene- 0.28 µg/l
Benzene- 6.2 µg/l; toluene- 6.8 µg/l; ethylbenzene-0.8 µg/l; biphenyl- 0.7 µg/l; fluorene- 0.7 µg/l; phenanthrene- 0.09 µg/l; anthracene- 0.02 µg/l; pyrene0.07 µg/l; chrysene- 0.21 µg/l; benzo[a ]pyrene- 0.08 µg/l
48
RI PT
Techniques
ChCl-phenol
1:4
500 µl
Tea
Residue resulted of wet digestion (0.5 g) added with 10 ml water
2 min
Ultrasonic bath; pH >6; 1 ml nitroso-2-naphthol; 0.5 ml THF
UALME
ChCl-phenol
1:3
450 µl
Waters (tap, lake, waste)
10 ml
2 min
UALME
ChCl:phenol:FeCl3
1:2:1
25 µl
n-heptane
1.5 ml
5 min
UALME
ChCl-phenol
1:2
100 µl
Waters (tap and industrial wastewater)
1.5 ml
20 min
Ultrasonic bath; 0.375 ml Chromium (III/VI) 0.5M H2 SO4 ; 0.4 ml 0.125% sodium diethyldithiocarbamate; 0.45 ml THF Ultrasonic bath (35 kHz) Thiophene 25°C Ultrasonic bath; 100 µl THF Benzene, toluene, ethylbenezene, PAHs (biphenyl, fluorene, phenanthrene, anthracene, pyrene, chrysene and benzo[a]pyrene)
UALME
ChCl-phenol
1:4
500 µl
2 ml
3 min
Ultrasonic bath; pH =3; 500 µl THF
Malachite green
UV-VIS
11.8 µg/l
3.6 µg/l
49
UALME
ChCl-Ox
1:1
1 ml
Waters (farmed and ornamental aquarium fish) Grape skin
100 mg freeze dried skin
50 min
Ultrasonic bath: 65 °C, 35 kHz; 25% water
Phenolics ((+)-Catechin, delphinindin-3O - glucoside, Cyanidin-3-O- glucoside, petunidin-3-O -glucoside, peonidin-3-O glucoside, malvidin-3-O -glucoside, quercetin-3-O -glucoside)
HPLC-UV
(+)-Catechin- 1.24 mg/l, delphinindin-3-O- glucoside- 0.60 mg/l, Cyanidin-3-O-glucoside0.71 mg/l, petunidin-3-Oglucoside- 0.80 mg/l, peonidin-3O-glucoside-0.65 mg/l, malvidin3-O-glucoside - 0.90 mg/l, quercetin-3-O-glucoside -0.46 mg/l
(+)-Catechin- 0.37 mg/l, delphinindin-3-O- glucoside- 0.18 mg/l, cyanidin-3-O-glucoside-0.21 mg/l, petunidin-3-O-glucoside0.24 mg/l, peonidin-3-O-glucoside0.19 mg/l, malvidin-3-O-glucoside - 0.30 mg/l, quercetin-3-Oglucoside -0.05 mg/l
42
UALME
tetramethylammonium chloride–ethylene glycol
1:3
30 µl
Saflower, olive,camellia, colza and soybean oils
1 ml (10 % oil - 90% hexane)
IAA -0.05 µg/ml; IBA -0.06 µg/ml; 4-IPOAA 0.75 µg/ml
45
UALME
Choline Chloride-Laevulinic Acid
1:2
1 ml
Platycladi Cacumen
25 mg
UAME
Choline chloride-malic acid
1:1
1 ml
Wine lees
33.3 mg
UAME
Choline chloride-glycerol
1:1
1 ml
tartary buckwheat hulls
UAME
Fructose-citric acid
1:1
1 ml
UAME
ChCl:citric acid
1.1
600 µl
Raw and processed food (spaghetti, biscuts, and ham) Soy products (soybeans, flour, pasta, breakfast cereals, cutlets, tripe, soy drink, soy nuts, soy cubes and three different dietary supplements)
MA
ChCl-1,2-propanediol
1:1
10 ml
M AN U
TE D
GC-FID
47
Ultrasonic bath -50°C
Plant growth regulators (IAA, IBA, 4IPOAA)
HPLC-UV
30 min
Ultrasonic bath: 50°C, 200 W; 75% water
Flavonoid glycosides and aglycones (myricitrin, quercitrin, amentoflavone, hinokiflavone) Anthocyanins
HPLC-UV
HPLC-DAD
Flavonoid (rutin)
HPLC-UV
58
Gluten
Enzyme Linked ImmunoSorbent Assay
55
Isoflavones (GT, DA, GTGL, daidzin DAGL)
UHPC-UV
DAGL- 0.40 µg/g; GTGL- 0.45 µg/g; DA- 0.25 µg/g; GT 0.20 µg/g
DAGL- 0.12 µg/g; GTGL- 0.14 µg/g; DA- 0.08 µg/g; GT 0.06 µg/g
56
Bioactive compou nds (ROS, LIT, SAB, SAA, TIIA)
HPLC-DAD
ROS- 0.80 µg/ml; LIT- 1.37 µg/ml; SAB- 1.96 µg/ml; SAA0.87 µg/ml; TIIA- 1.45 µg/ml
ROS- 0.24 µg/ml; LIT- 0.49 µg/ml; SAB- 0.62 µg/ml; SAA- 0.31 µg/ml; TIIA- 0.48 µg/ml
60
EP
7 min
30.6 min
Ultrasaound bath: 341.5 W, 37 kHz, 35°C ; 35.4% water
40 mg
1h
25 mg
15 min
200 mg
60 min
Ultrasaound bath: 20 kHz, 200 W, 40 °C; 20% water Ultrasound bath (100 w 42 kHz) 40% amplitude; 20% water Ultrasonic bath: 440 W, 60°C; 30% water
50 mg
11.11 min
AC C
Radix Salviae miltiorrhizae
SC
UALME
Microwave: 800W, 70°C
43
Delphinidin-3-O glucoside- 0.87 Delphinidin-3-O glucoside- 0.28 mg/l; cyanidin-3-O glucosidemg/l; cyanidin-3-O glucoside0.52 mg/l; petunidin-3-O 0.17 mg/l; petunidin-3-O glucoside- 0.44 mg/l; peonidin-3- glucoside- 0.15 mg/l; peonidin-3O glucoside- 0.62 mg/l; malvidin- O glucoside- 0.2 mg/l; malvidin-33-O glucoside- 0.81 mg/l O glucoside- 0.25 mg/l
57
ACCEPTED MANUSCRIPT
Time Simplicity + ++ ++ + ++ + + + ++ + ++
Low Solvent Volume + + ++ ++ ++ ++
M AN U
(-), less favourable; (+), favourable; (++), more favourable
Cost + + ++ + + -
Common instrument analysis HPLC HPLC and GC HPLC and GC HPLC and GC HPLC, spectrophotometry, Immunoassay HPLC
SC
Technique LPME DLLME AG-DLLME and AAELLME HPLME UAME MAE
RI PT
Table 4- Overall performance of extraction techniques based on the use DES/NADES solvents Greenness + + + + ++ +
AC C
EP
TE D
LPME, liquid-phase microextraction; DLLME, dispersive liquid-lquid microextraction; AG-DLLME, gas air-dispersive liqui-lquid microextraction; AAELLME,air-assisted liquid-liquid microextraction; HPLME, hollow fiber-liquid phase microextraction; UAME, ultrasound-assisted microextraction; MAE, microwave-assisted Extraction; HPLC, high performance liquid chromatography; GC, gas chromatography
ACCEPTED MANUSCRIPT
Fig 1 18 16 14 12 10 8 6
100 50 0
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
year
TE D
Web of Science Categories ENERGY FUELS ELECTROCHEMISTRY CHEMISTRY ANALYTICAL
EP
THERMODYNAMICS PHYSICS ATOMIC MOLECULAR CHEMICAL
GREEN SUSTAINABLE SCIENCE TECHNOLOGY ENGINEERING CHEMICAL CHEMISTRY PHYSICAL CHEMISTRY MULTIDISCIPLINARY 0
5
10
15
20
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
year
Web of Science Categories
Chemistry AppliedCHMEISTRY APPLIED BIOCHEMISTRY MOLECULAR BIOLOGY PLANT SCIENCES FOOD SCIENCE TECHNOLOGY CHEMISTRY MEDICINAL GREEN SUSTAINABLE SCIENCE…
AC C
MATERIALS SCIENCE MULTIDISCIPLINARY
4 2 0
SC
20
450 400 350 300 250 200 150
Number of publications
500
RI PT
NADES
M AN U
Number of publications
DES
PHARMACOLOGY PHARMACY ENGINEERING CHEMICAL CHEMISTRY ANALYTICAL CHEMISTRY MULTIDISCIPLINARY 25
30
35
% of publication from a total of 1303
0
5
10
15
20
25
30
% of publication from a total of 56
ACCEPTED MANUSCRIPT Highlights DES and NADES are environmentally-friendly alternative to organic solvents Novel applications of DES and NADES in microextraction techniques for food, biological and environmental analysis are described Recent microextraction techniques based in DES/NADES are compared with earlier approaches
AC C
EP
TE D
M AN U
SC
RI PT
Future perspectives of DES/NADES in microextraction techniques are stated