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Journal of Chromatography A, 1335 (2014) 2–14

Contents lists available at ScienceDirect

Journal of Chromatography A

jo ur nal ho me pag e: www.elsev ier .com/ locate /chroma

eview

eyond dispersive liquid–liquid microextraction

ei-I. Leonga, Ming-Ren Fuhb,1, Shang-Da Huangc,∗

Centro de Seguranca Alimentar, Instituto para os Assuntos Cívicos e Municipais (IACM), Macau, ChinaDepartment of Chemistry, Soochow University, Taipei 11102, TaiwanDepartment of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan

r t i c l e i n f o

rticle history:eceived 24 October 2013eceived in revised form 9 February 2014ccepted 10 February 2014vailable online 15 February 2014

eywords:ispersive liquid–liquid microextractionispersion liquid-phase microextractionreconcentrationample preparation

a b s t r a c t

Dispersive liquid–liquid microextraction (DLLME) and other dispersion liquid-phase microextraction(LPME) methods have been developed since the first DLLME method was reported in 2006. DLLMEis simple, rapid, and affords high enrichment factor, this is due to the large contact surface area ofthe extraction solvent. DLLME is a method suitable for the extraction in many different water sam-ples, but it requires using chlorinated solvents. In recent years, interest in DLLME or dispersion LPMEhas been focused on the use of low-toxicity solvents and more conveniently practical procedures. Thisreview examines some of the most interesting developments in the past few years. In the first sec-tion, DLLME methods are separated in two categories: DLLME with low-density extraction solvent andDLLME with high-density extraction solvent. Besides these methods, many novel special devices for col-lecting low-density extraction solvent are also mentioned. In addition, various dispersion techniqueswith LPME, including manual shaking, air-assisted LPME (aspirating and injecting the extraction mix-ture by syringe), ultrasound-assisted emulsification, vortex-assisted emulsification, surfactant-assistedemulsification, and microwave-assisted emulsification are described. Besides the above methods, com-

binations of DLLME with other extraction techniques (solid-phase extraction, stir bar sorptive extraction,molecularly imprinted matrix solid-phase dispersion and supercritical fluid extraction) are introduced.The combination of nanotechnique with DLLME is also introduced. Furthermore, this review illustratesthe application of DLLME or dispersion LPME methods to separate and preconcentrate various organicanalytes, inorganic analytes, and samples.

© 2014 Elsevier B.V. All rights reserved.

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.1. DLLME with lower-density extraction solvent. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

1.1.1. DLLME based on solidification of floating organic droplet (DLLME-SFO) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.1.2. DLLME with special extraction devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51.1.3. Low-density-solvent based solvent demulsification DLLME (LDS-SD-DLLME). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

1.2. DLLME with higher-density extraction solvent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71.2.1. DLLME with low-toxicity solvent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71.2.2. Auxiliary solvent to adjust the density of DLLME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71.2.3. DLLME with automated online sequential injection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2. Development of DLLME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.1. Various techniques for assisting dispersion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.1.1. Manual shaking for assisting dispersion . . . . . . . . . . . . . . . . .

2.1.2. Air-assisted liquid–liquid microextraction (AALLME) . . .

2.1.3. Ultrasound-assisted emulsification . . . . . . . . . . . . . . . . . . . . . .

∗ Corresponding author. Tel.: +886 3 572 1194; fax: +886 3 573 6979.E-mail addresses: msfuh@mail.scu.edu.tw (M.-R. Fuh), sdhuang@mx.nthu.edu.tw (S.-D

1 Tel.: +886 2 2881 9471x6821; fax: +886 2 2881 1053.

ttp://dx.doi.org/10.1016/j.chroma.2014.02.021021-9673/© 2014 Elsevier B.V. All rights reserved.

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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

. Huang).

M.-I. Leong et al. / J. Chromatogr. A 1335 (2014) 2–14 3

2.1.4. Surfactant-assisted emulsification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.1.5. Vortex-assisted emulsification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92.1.6. Microwave-assisted emulsification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.2. Combination of techniques for extraction and analysis with DLLME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102.2.1. Solid-phase extraction combined with DLLME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102.2.2. Stir bar sorptive extraction (SBSE) combined with DLLME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112.2.3. Molecularly imprinted matrix solid-phase dispersion combined with DLLME (MIM–MSPD–DLLME) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112.2.4. Supercritical fluid extraction (SFE) combined with DLLME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112.2.5. Nanotechniques combined with DLLME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

2.3. Other methods using low-toxicity solvent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113. DLLME applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

3.1. Application of DLLME for various analytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.1.1. Organic compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.1.2. Inorganic compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

3.2. Application of DLLME to various field samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

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References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. Introduction

Liquid–liquid microextraction (LPME) is usually applied in thextraction of environmental samples. LPME has several differentperational modes, such as those that use a drop of solvent [1,2],orous hollow fiber-protected solvent [3–5], and disperser sol-ent. The first two methods are simple and use lower volumes ofrganic solvent. However, they are limited by the small contacturface area of the drop or fiber, which necessitates long extrac-ion times. In 2006, Rezaee et al. developed dispersive liquid–liquid

icroextraction (DLLME) for preconcentration of polycyclic aro-atic hydrocarbons (PAHs) in water samples [6]. The first DLLMEethods employ a mixture of a high-density extraction solvent, aater-miscible solvent, and a polar disperser solvent. The extrac-

ion solvent must be able to extract analytes, is soluble in theisperser solvent, insoluble in aqueous samples, and have densityigher than that of water. The disperser solvent has to be soluble

n both water and extraction solvent. In this method (Fig. 1(a)) [6], mL of the aqueous solution is placed in a screw-cap glass test tubeith a conical bottom. A solution of 1 mL of acetone (disperser sol-

ent) and 8 �L of tetrachloroethylene (TCE, the extraction solvent)s injected into the sample solution. A cloudy dispersion consist-ng of water, disperser solvent, and extraction solvent is formed inhe test tube and is centrifuged. The dispersed fine droplets of thextraction phase settle at the bottom of the conical test tube andould be injected into a gas chromatograph for further analysis.any conventional DLLME typically use 20–100 �L of chlorinated

olvents as extraction solvent, 0.5–2 mL of disperser solvent, and–10 mL of aqueous sample. The total extraction time including theentrifugation time is generally 5–10 min. Advantages of this tech-ique include simplicity of operation, rapid extraction, and highnrichment factors (EFs) [7,8]. However, the high-density extrac-ion solvent used, which is typically chlorobenzene, chloroform, orarbon tetrachloride, is highly toxic.

There are many excellent recent reviews on DLLME or disper-ion LPME methods (methods that disperse extraction solvent forxtraction) [9–13]. Kocúrová et al. summarized a lot of details aboutLLME using organic solvents lighter than water methods, and con-ludes the uses of special devices, the low-density solvent usedbased on solidification and solvent demulsification) in DLLME pro-edures, the adjustment of extraction solvents mixture density and

rocedures based on automation of DLLME by sequential injectionnalysis [9]. Zgoła-Grzeskowiak and Grzeskowiak described thepplication of DLLME to pre-concentration of metal ions, pharma-euticals, other organic compounds and many more modifications

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

of these newly developed techniques [10]. Kokosa reviewed thedevelopment of DLLME and summarized the techniques in threecategories: DLLME using extraction solvents with density greaterthan water, DLLME using extraction solvents with density lowerthan water and automated DLLME [11]. Asensio-Ramos et al. sum-marized several DLLME applications in food analysis. Analytes canbe initially extracted from the food matrix with an organic sol-vent, which normally acts in a second step as the disperser solvent[12]. Dadfarnia and Shabani summarized and discussed the applica-tion of DLLME in combination with different analytical techniquesfor preconcentration and determination of ultra trace amounts ofmetals and organometal ions in various matrices [13]. This reviewsummarized and discussed the recent developments of DLLME anddispersion LPME including the utilization of various less toxic sol-vents, development various techniques to increase rate of masstransfer between two extracting solvent and sample solution, com-bination of other extraction with DLLME and design of specialdevice for DLLME. Abbreviations of the DLLME and dispersion LPMEmethods in this review are shown in Table 1.

Depending on the extraction solvent used, DLLME method maybelong to one of two broad categories: those that use a lower-density extraction solvent and those that use a higher-densityextraction solvent. Many new techniques in the former categoryhave been introduced to separate and collect the extraction sol-vent from sample solution. Brominated or iodinated solvents andan auxiliary solvent in the latter category have been introduced;these methods enable easy separation of extraction solvent andsamples solution by centrifugation. Other novel online and auto-mated procedures with DLLME that have a promising future inanalytical methodology are also mentioned in this section.

1.1. DLLME with lower-density extraction solvent

1.1.1. DLLME based on solidification of floating organic droplet(DLLME-SFO)

Liquid–liquid microextraction based on solidification of floatingorganic droplet (LLME-SFO) was introduced by Khalili-Zanjani et al.[14,15]. It is simple, inexpensive, and it involves minimal consump-tion of organic solvent. However, its extraction rate is lower thanthat of DLLME. DLLME-SFO [16,17] was developed to combine the

benefits of DLLME and LLME-SFO. Unlike LLME-SFO, DLLME-SFOdoes not involve stirring during extraction, and unlike traditionalDLLME, it does not use chlorinated solvents and conical bottomglass tubes. Instead, a mixture of low-toxicity extraction solvent

4 M.-I. Leong et al. / J. Chromatogr. A 1335 (2014) 2–14

Fig. 1. Diagram of the extraction process of (a) DLLME and (b) DLLME-SFO.

Table 1The abbreviations of the DLLME and dispersion LPME methods in this review.

Method Abbreviation of the method Ref.

Dispersive liquid–liquid microextraction DLLME [6]

DLLME with lower density extraction solventDLLME based on the solidification of a floating organic drop DLLME-SFO [16,17]Ionic liquid-based up-and-down shaker-assisted DLLME UDSA-IL-DLLME [25]Low-density solvent-based solvent demulsification DLLME LDS-SD-DLLME [26]

DLLME with higher density extraction solventLow toxic DLLME LT-DLLME [28]Adjust the density of DLLME AS-DLLME [29]Injection dispersive liquid–liquid microextraction SI-DLLME [30–33]

Various techniques for assisting dispersionDLLME with a very low solvent consumption DLLME–LSC [34]Air-assisted liquid–liquid microextraction AALLME [35]Ultrasound-assisted emulsification microextraction USAEME [36–45]Surfactant assisted DLLME SA-DLLME [22,23]Coacervative microextraction ultrasound-assisted back-extraction technique CME-UABE [39]Water with low concentration of surfactant in dispersed solvent-assisted emulsion dispersive

liquid–liquid microextractionWLSEME [46]

Low-density solvent-based vortex-assisted surfactant-enhanced-emulsification liquid–liquidmicroextraction

LDS–VSLLME [48]

Vortex-assisted supramolecular solvent microextraction VASUSME [49]Vortex-assisted liquid–liquid microextraction VALLME [38,47–49]Homogeneous ionic liquid microextraction HILME [50]

Combination of techniques for extraction and analysis with DLLMESolid-phase extraction combined with DLLME SPE + DLLME [51]Stir bar sorptive extraction combined with DLLME SBSE + DLLME [52]Matrix solid-phase dispersion combining with DLLME MSPD–DLLME [53]Supercritical fluid extraction followed by DLLME SFE + DLLME [54,55]Dispersive microsolid-phase extraction combined with DLLME D-�-SPE + DLLME [56,57]Vortex-assisted micro-solid-phase extraction followed by low-density solvent based DLLME VA-�-SPE + LDS-DLLME [58]

Other methods using low-toxicity solventFlotation-assisted homogeneous liquid–liquid microextraction FA-HLLME [76]

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which is also less dense than water) and disperser solvent areapidly injected into the sample solution to form a cloudy disper-ion in the glass test tube. In this method [16] (Fig. 1(b)), a mixturef 0.5 mL of acetone and 10 �L of 2-dodecanol is rapidly injected byyringe into a 5 mL water sample. After centrifugation, the test tubes transferred to a beaker containing crushed ice, and the solidi-ed solvent is easily collected for analysis. To meet recent concernsbout the costs and environmental hazards of waste solvent dis-osal, this method uses an extraction solvent of low toxicity and

ow volatility. The large contact surface area between the samplend the droplets of extractants facilitate mass transfer, resulting inxtraction times similar to those of DLLME and shorter than that ofLME-SFO [14,15,18]. The drawbacks of this method are limited tohe solvent chosen (low melting point) which is suitable for use inarm climates, if the laboratory is not air conditioned.

.1.2. DLLME with special extraction devicesRecently, many researchers have attempted to use lower-

oxicity solvents with density lower than that of water in DLLME.ne possible way of enabling the application of such solvents inLLME is the use of special extraction devices, such as speciallyesigned centrifugation tubes and pipette collection tubes. In 2009,arajzadeh et al. designed a special vessel [19] for use in DLLMEo extract organophosphorus pesticides (OPPs) (Fig. 2(a)). In thisxtraction method, a mixture of cyclohexane (extraction solvent)nd acetone (disperser solvent) is rapidly injected by syringe inton aqueous sample in a special vessel. After centrifugation, fineroplets of cyclohexane accumulate in the upper layer of aqueousolution. The upper phase is injected into a gas chromatograph foreparation. This method is rapid and easily recovers the extrac-ant; however, it is not suitable for extracting volatile compounds.ashemi et al. developed a DLLME method that uses a specialevice to enrich glycyrrhizic acid from aqueous extracts of licoriceFig. 2(b)) [20]. The device consists of a narrow-necked glass tubeNNGT) inserted into a centrifuge tube. Hexanol and acetone aresed as the extraction solvent and disperser solvent, respectively.

uniformly distributed cloudy suspension is produced by furtherspiration and expulsion of about 2 mL of the cloudy sample byyringe. The mixture is then centrifuged for phase separation. Sinceexanol is lighter than water, the extraction phase accumulates onhe surface of the aqueous solution. Additional water is added fromhe opening of NNGT; then, the extraction phase is raised and fillshe narrow neck of NNGT. As a result, the extraction phase can easilye withdrawn by microsyringe.

Saleh et al. reported a centrifuge glass vial fabricated in-houseor ultrasound-assisted emulsification microextraction (USAEME)Fig. 2(c)) for the determination of PAHs in water samples [21]. Inhis method, the extraction solvent toluene is injected slowly intoqueous sample in a centrifuge glass vial in an ultrasonic waterath. After centrifugation, the separated toluene is injected into

gas chromatograph for analysis. This method affords very rapidxtraction and recovery of the extractant. The only drawback ofhis and the aforementioned method by Hashemi et al. [20] is theifficulty of cleaning the centrifuge glass vial. In 2011, Zhang et al.esigned a special flask equipped with two narrow open ports, onef which has a capillary tip [22] to extract ultraviolet (UV) filtersn environmental water samples (Fig. 2(d)). The flask is employedo facilitate the DLLME process. 1-Octanol, a low-density solvent,s used as the extraction solvent for DLLME and no disperser sol-ent is used. The extraction is accelerated by magnetic agitation.fter extraction, no centrifugation step is necessary, and phaseeparation of the extraction solvent from the aqueous sample is

asily achieved by allowing the extraction mixture to stand sev-ral minutes. The organic phase rises to the top of the mixture andoncentrates in the narrow open tip of the flask upon addition ofure water into the extraction mixture through the other port. It

gr. A 1335 (2014) 2–14 5

is thereafter withdrawn by microsyringe for HPLC analysis. Thismethod is faster than many DLLME methods because it does notrequire centrifugation. It can be applied in the extraction of samplesthat are non-volatile and have large volumes. Hu et al. developed[23] a DLLME method based on a molecular complex for analysisof polar compounds in aqueous solution (Fig. 2(e)). The principle ofthis method is the hydrogen bonding between the extractant andthe analytes. In this approach, the Lewis base tri-n-butylphosphate(TBP) instead of conventional water-immiscible organic solventsis directly used as extractant for DLLME. The sample containingthe analytes is placed in a disposable polyethylene pipette. A mix-ture of the extractant TBP and the disperser solvent methanol israpidly injected into the sample solution by syringe. Subsequently,the pipette is placed in a 10 mL Eppendorf tube and is agitated by avortex mixer. After centrifugation, the organic phase floating on theaqueous solution is concentrated in the narrow neck of the pipette,and is easily withdrawn by a 10.0 �L microsyringe. This techniqueexpands the application of classical DLLME for various organic ana-lytes, and enables extraction in a disposable polyethylene pipette.Su and Jen developed an in-syringe USAEME for the extraction ofOPPs from water samples by using GC with micro electron capturedetection [24] (Fig. 2(f)). Ultrasound radiation is applied to acceler-ate the emulsification of microliter volumes of low-density organicsolvent in aqueous solutions to enhance the efficiency of OPPsmicroextraction from the sample. Initially, the sample solution isdrawn into a 5 mL syringe. After removal of the plunger and sealingof the syringe with a silicone-plug, the barrel is held upside downand the needle is removed. The extraction solvent (toluene) is theninjected into the sample solution by using a 100 �L glass syringe.After ultrasonication and centrifugation, the plunger of the 5 mLsyringe is slowly pushed to transfer the recovered extractant intoa graduated capillary tube. Finally, the extracting phase containingthe target OPPs is easily recovered by syringe. One microliter of theseparated extractant is injected into GC for analysis. This methoduses a 5 mL syringe as the sample vial instead of a centrifuge tube,and a 100 �L glass syringe is used to inject the extraction solventand to recover the extractant. This device is easy to operate, andthe extractant volume is easily read from the scale on the capillarytube. This method does not require a narrow-necked port to collectthe extractants and the device is very easy to clean.

To save time and effort, Ku et al. performed an up-and-downshaker assisted DLLME that uses an ionic liquid (IL) to pre-concentrate three UV filters from field water samples [25]. Theup-and-down shaker model FS-6 was used to shake the mixtureof extraction solvent and aqueous sample. In this method, a holderfabricated in-house is used to hold the sealed conical-bottom glasstubes. The extraction solvent 1-octyl-3-methylimidazolium hex-afluorophosphate ([C8MIM][PF6]) (40 �L) and the disperser solventmethanol (200 �L) are used to extract the UV filters. After up-and-down shaking for 3 min, the aqueous mixture is centrifuged, andthen a microtube is used to collect the extraction solvent for fur-ther analysis by ultra-performance liquid chromatography (UPLC).The apparatus for this method is simple and the extraction timeis less than 4 min. This method also addresses the variation of theshaking process due to different operators. In addition, an IL of lowtoxicity such as [C8MIM][PF6] is used instead of the highly toxicsolvent normally used in DLLME.

Dispersions in various special extraction devices are describedin Table 2. The use of the narrow parts (neck, port, or nozzle) ofdevices can assist the collection of the low-density extraction sol-vent from the samples. Most of the devices use narrow necks orports to gather the extractant drops [19–22]. Before removal of the

extractant, water must be injected to allow the extracted organicdrop to reach the level of the neck or port of the tube or flask.Other methods that use the nozzle of a pipette [23] or syringe [24]to gather the extractant do not require injection of water and the

6 M.-I. Leong et al. / J. Chromatogr. A 1335 (2014) 2–14

Fig. 2. Diagram of the special device used in dispersion LPME with low-density extraction solvent: (a) special extraction vessel (DLLME), (b) glass tube with narrow neck(DLLME), (c) centrifuge glass vial designed in-house (USAEME), (d) special flask equipped with two narrow open ports (DLLME), (e) 5 mL polyethylene Pasteur pipette (DLLME),(f) 5 mL syringe as sample vial (DLLME) and (g) disposable polyethylene pipette (LDS-SD-DLLME).

M.-I. Leong et al. / J. Chromatogr. A 1335 (2014) 2–14 7

Table 2Dispersion in different special extraction devices.

Fig. 2 Special sample vessel/tube/vial Method Instrumentation Analytes Extraction solvent Ref.

(a) A special extraction vessel DLLME GC-FID OPPs Cyclohexane [19](b) A glass tube with a narrow neck DLLME HPLC Glycyrrhizic acid n-Hexanol [20](c) A home-designed centrifuge glass vial USAEME GC-FID PAHs Toluene [21](d) A special flask equipped with two narrow open ports DLLME HPLC UV filters 1-Octanol [22]

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xtraction apparatus is easy to clean. Except for the methods thatse a special flask [22] for magnetic agitation or use an up-and-own shaker [25] to disperse the extraction solvent, there are manyxtraction methods use disperser solvent or surfactant to assist theispersion of the extraction solvent.

.1.3. Low-density-solvent based solvent demulsification DLLMELDS-SD-DLLME)

All of the aforementioned extraction devices possess advan-ages and drawbacks in terms of ease of operation and manifoldomplexity. Guo and Lee [26] reported a LDS-SD-DLLME methodor the determination of 16 priority PAHs in environmental sam-les (Fig. 2(g)). No centrifugation is required in this procedure.

5 mL sample solution is placed in a 5 mL polyethylene Pasteuripette by using a 5 mL syringe. A mixture of the extraction solvent-hexane (50 �L) and the dispersive solvent acetone (500 �L) is

njected rapidly into the sample solution by a 1.0 mL syringe to formn emulsion. The demulsification solvent acetone (500 �L) is thennjected into the aqueous solution to break up the emulsion andeparate it into two layers. The upper layer (about 35 �L n-hexane)s collected and analyzed by gas chromatography–mass spectrom-try (GC–MS). Notably, the extraction requires only 2–3 min, ands therefore faster than conventional DLLME or similar techniques.his method permits a solvent that is less dense than water to besed as extraction solvent, and expands the applicability of DLLMEo a wider range of solvents.

Chang et al. used DLLME combined with an improved solventollection system to separate water and organic solvent in theollected extractant drop [27]. This method uses very small vol-mes of low-toxicity solvents (11 �L of 1-nonanol and 400 �L ofethanol) to extract organochlorine pesticides (OCPs) from 10 mLater samples prior to analysis by GC. After centrifugation, a liquid

rganic drop accumulates between the water surface and the glassall of the centrifuge tube. The liquid organic drop is transferred

long with some of the water into a microtube (3 mm × 15 mm) byyringe. The organic and aqueous phases then immediately sep-rate in the microtube. The organic solvent is easily collected byyringe and then injected into the GC instrument for analysis. More-ver, it is better to centrifuge the collected phases in the microtubeor about 1 min before injection, because it further removes water;n this manner, two clear phases are obtained. This improved sol-ent collection system can protect the instrument from damage byhe injected water and increase the reproducibility of the results.

.2. DLLME with higher-density extraction solvent

.2.1. DLLME with low-toxicity solventIn addition to the many DLLME methods that have been

eveloped to use low-density organic solvents, other methodssing higher-density extraction solvent have been introduced tovercome the drawbacks of normal DLLME. In 2010, LT-DLLME

as developed by Leong et al. [28]. This method uses lower-

oxicity brominated, iodinated and other halogenated solventsuch as 1-bromo-3-methylbutane (1-bromo-3-methylbutane,he median lethal dose (LD50) 6150 mg kg−1) instead of the

GC-�ECD OPPs Toluene [23]HPLC Phenols TBP [24]GC–MS PAHs n-Hexane [26]

highly toxic solvents normally used in DLLME. This method alsodemonstrates that propionic acid is suitable as a disperser solvent;as little as 50 �L of the acid is sufficient for extraction. A 7 mL sam-ple of water is spiked with PAHs. The disperser solvent propionicacid and the extraction solvent 1-bromo-3-methylbutane (10.0 �L)are rapidly injected into the sample solution and the resultingmixture is shaken by hand for a few seconds. Potassium hydroxide(88 �L, 40% (w/v)) is added to the sample to minimize emulsionformation by the extraction solvent before centrifugation. Aftercentrifugation, the organic solvent is sedimented at the bottom ofthe conical test tube, and then a microsyringe is used to collect andinject it into a gas chromatograph for further analysis. The selectedextraction solvent is less toxic than chlorinated solvents in normalDLLME. In particular, some brominated solvents are less toxic thanthe conventional low-density solvents in DLLME or dispersionLPME.

1.2.2. Auxiliary solvent to adjust the density of DLLMEKocúrová et al. [29] developed an adjusting-density DLLME (AS-

DLLME) technique. A quaternary system consisting of an aqueoussample, an extraction solvent, an auxiliary solvent, and a dispersersolvent is employed in this method. The auxiliary solvent (a chlo-rinated solvent), which is denser than water, is used to adjust thedensity of the extraction solvent–auxiliary solvent mixture to facil-itate its separation from the aqueous sample by centrifugation.This method does not require the use of special devices. A 5 mLsample solution containing Au (III) is prepared in conical microcen-trifuge tubes. A 0.5 mL mixture of the disperser solvent methanol,the extraction solvent toluene (145 �L), and the auxiliary solventcarbon tetrachloride (CCl4; 145 �L) is vigorously injected by using a0.5 mL glass syringe. The mixture is gently shaken and centrifuged.A layer of sediment containing a mixture of toluene and CCl4 accu-mulates at the bottom of the tube. The extractant is removed bysyringe and then analyzed by UV–visible spectrometer. Alterna-tively, the extractant may be transferred to a graphite atomizer foratomic absorption spectroscopy. This novel method combines theadvantages of conventional DLLME and the use of lower-densitysolvent and lower volumes of toxic solvents.

1.2.3. DLLME with automated online sequential injectionAnthemidis and Ioannou developed an automated on-line

sequential injection dispersive liquid–liquid microextraction SI-DLLME system for metal preconcentration [30–32] (Fig. 3(a)). Themixture of disperser solvent, extraction solvent, and chelatingagent is mixed with a stream of aqueous sample through an onlinesystem. After extraction, droplets of the organic phase are retainedin a microcolumn. The eluent is then transferred by a nebulizer foranalysis by flame atomic absorption spectrometry (FAAS) analysis[30,31], or injected into a graphite tube for electrothermal atomicabsorption spectrometry (ETAAS) measurement [32]. This methoddoes not require centrifugation and an extraction solvent that is

denser than water, and the process is fully automated. However,this method requires a microcolumn for retention of the analytesand several hundred microliters of solvents for elution of the ana-lytes. Andruch et al. [33] reported a novel SI-DLLME (Fig. 3(b)). In

8 M.-I. Leong et al. / J. Chromato

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he method, sample and all reagents are drawn into the holdingoil of the sequential injection analysis (SIA) manifold, and theesulting mixture is delivered into a conical tube. A mixture ofhe extraction solvent is then added at a high flow rate to form aloudy suspension and to extract the analytes. The extraction phaseonsequently separates rapidly at the bottom of the conical tube.fterward, the extraction phase is transferred to a microvolume-flow cell for spectrophotometric detection. The online DLLMEethods achieved a major breakthrough in DLLME and overcame

he difficulties of rapidly extracting analytes and collecting therganic solvent in online analysis.

. Development of DLLME

Recent trends in DLLME include the use of lower volumes of lessoxic solvents and techniques for dispersing extraction solvents andqueous samples rapidly. Table 3 shows the extraction solvents andxtraction times for various techniques.

.1. Various techniques for assisting dispersion

.1.1. Manual shaking for assisting dispersionTsai and Huang reported DLLME with very low consumption of

olvent (DLLME–LSC) method [34]. In DLLME-LSC, much less vol-me of organic solvent is used as compared with DLLME. A 10 mL

queous sample spiked with each targeted OCP is transferredo a glass centrifuge tube with conical bottom. Sodium chloride300 mg) is added to the glass tube and dissolved completely. A3 �L mixture of the extraction solvent TCE and the disperser

gr. A 1335 (2014) 2–14

solvent diethyl ether at a ratio of 6:4 is added to the tube, andthen the tube is shaken vigorously for 90 s. Fine organic dropletsare subsequently formed in the sample solution by manuallyshaking the test tube containing the mixture of sample solutionand extraction solvent. The large surface area of the organic solventdroplets increases the rate of mass transfer from the water sampleto the extractant, and allows efficient extraction in a short period.This method is a rapid and convenient procedure for qualitativeand quantitative analyses of OCPs. Manual shaking may be done fordispersion and extraction, or as a premixing step before extraction.

2.1.2. Air-assisted liquid–liquid microextraction (AALLME)Farajzadeh and Mogaddam developed an AALLME method for

extraction and preconcentration of phthalate esters from aque-ous samples prior to GC analysis [35]. In this method, fine organicdroplets are formed by aspirating and expelling the mixture ofaqueous sample solution and extraction solvent by syringe for sev-eral times in a conical test tube. After extraction, phase separation isperformed by centrifugation, and the enriched analytes are deter-mined by GC–FID. This method requires less volume of organicsolvent and does not use a disperser solvent. The extraction solventis dispersed by aspiration and expulsion of the sample mixture bysyringe instead of using disperser solvent. It is simple, requires lit-tle organic solvent, and is suitable for extraction of various organiccompounds in aqueous samples.

2.1.3. Ultrasound-assisted emulsificationUltrasound-assisted [36,37] and vortex-assisted emulsification

[24,38] reduce the consumption of solvent. Regueiro et al. [36] andFontana et al. [37] developed USAEME for concentration of analytes.Ultrasound-assisted emulsification has been found to improve effi-ciency by increasing the rate of mass transfer between the twoimmiscible phases. In 2008, Regueiro et al. developed a novelmethod based on USAEME and GC–MS for the analysis of syntheticmusk fragrances (Fig. 4(a)) [36]. In their method, a 10 mL sample isplaced in a 15 mL conical-bottom glass centrifuge tube, and 5 ng ofthe surrogate standard PCB-166 in acetone is added to the sam-ple. A 100 �L solution of 5 ng of PCB-195 (internal standard) inchloroform is added as extractant. The tube is then immersed inan ultrasonic water bath (40 kHz ultrasound frequency and 100 Wpower for 10 min at 25 ± 3 ◦C). The resulting emulsion is then dis-rupted by centrifugation and the organic phase is sedimented atthe bottom of the conical tube. Chloroform is removed by using asyringe and the remaining extract is transferred to a 100 �L glassinsert in a 1.8 mL GC vial. Extracts are stored at −20 ◦C until analysisby GC–MS. USAEME is an efficient, simple, rapid, and inexpen-sive alternative to other extraction techniques such as solid-phaseextraction (SPE), solid phase microextraction (SPME), and LPME. Asimilar approach of extraction reported by Fontana et al. uses ultra-sound and surfactant [39]. It is environmentally friendly because ofthe low consumption of organic solvent.

However, ultrasound-assisted emulsification for extendedperiods may lead to decomposition of analytes. A number of reportsindicated that the use of manual shaking in USAEME improvesthe extraction efficiency and lowers the ultrasonic extraction time,which minimizes decomposition of analytes [40,41]. Lin and Fuhused ultrasound with occasional manual shaking to form a cloudysuspension, and obtained good results [42]. Other fast and novelUSAEME methods that use low-density solvent were developed byLee’s group [43–45].

2.1.4. Surfactant-assisted emulsification

Surfactant-assisted DLLME (SA-DLLME) [22,23] followed by

HPLC has been developed for the extraction and determinationof chlorophenols in environmental water samples (Fig. 4(b)). Inthis approach, the cationic surfactant cetyltrimethylammonium

M.-I. Leong et al. / J. Chromatogr. A 1335 (2014) 2–14 9

Table 3Extraction solvent and extraction time of different dispersion techniques.

Dispersion techniques Method Extraction solvent Extraction time (min) Ref

Manual shaking DLLME-LSC TCE 1.5 [34]Air-assisted emulsification AALLME Chloroform <0.5 [35]Ultrasound-assisted emulsification USAEME Chloroform 10 [36]Surfactant assisted emulsification SA-DLLME 1-Octanol 3 [22]Vortex-assisted emulsification VALLME Octanol 2 [38]Low-density solvent-based vortex-assisted surfactant-enhanced-emulsification LDS–VSLLME Toluene 1 [48]

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Vortex-assisted supramolecular solvent microextraction

Homogeneous ionic liquid microextraction

romide (CTAB) is used as a dispersing agent. An extraction sol-ent is injected rapidly into the aqueous sample containing CTAB,nd the resulting mixture is shaken for 1–3 min to disperse therganic phase. After extraction, the mixture is centrifuged and the

ig. 4. Diagram of the extraction process of (a) USAEME, (b) VALLME, and (c) HLLE.

ASUSME Octyl alcohol and THF 2 [49]ILME [C4MIM][PF4] 6 [50]

organic phase is subjected to HPLC analysis. In addition, coacerva-tive ultrasound-assisted back-extraction was developed to extractand preconcentrate OPPs from honey samples prior to GC–MS [39].In this method, an aliquot of 10 mL 50 g L−1 honey blend solutionis conditioned by addition of 100 �L of 0.1 mol L−1 hydrochlo-ric acid (pH 2) and 100 �L of 100 g L−1 Triton X-114 and manualshaking of the mixture. After several steps, ultrasound-assistedback-extraction is done by addition of extraction solvent. One ofthe major drawbacks of SA-DLLME is that some of the surfactantis also extracted from the aqueous sample into the extraction sol-vent; as a result, it may limit the selection of detection methods foranalytes. Li et al. developed a SA-DLLME method that uses waterwith low concentration of surfactant in dispersed solvent-assistedemulsion to decrease the volume of surfactant used in extraction;consequently, surfactant in the final extractant is greatly reduced[46].

2.1.5. Vortex-assisted emulsificationIn 2010, Yiantzi et al. described vortex-assisted liquid–liquid

microextraction (VALLME) for the analysis of alkylphenols [38].The analytes were agitated with a vortex mixer, which acceler-ated mass transfer to the organic phase. The extractant octanol(50 �L) was mixed with 20 mL of aqueous sample without adjust-ing the ionic strength or pH. The vortex agitator was set at 2500 rpmfor 2 min extraction time. After centrifugation, the floating octanolphase was easily collected with a microsyringe. Ultrasound-assisted and vortex-assisted emulsification reduced the volumeof organic solvent required. Compared with ultrasound-assistedemulsification, homogenization or emulsification with ultrasoundwas faster because formation of submicron droplets greatlyincreased the contact surface between the two liquids, resultingin fast and efficient analyte transfer. However, ultrasound-assistedemulsification for extended periods may cause analytes to decom-pose.

Zhang and Lee developed VALLME [47] and vortex-assistedsurfactant-enhanced-emulsification liquid–liquid microextractionbased on low-density solvent (LDS-VSLLME) [48]. In this method,the sample solution is injected into a mixture of the extractionsolvent toluene and the surfactant CTAB. The resulting mixture istransferred to a glass tube with conical bottom and then vortexedto form an emulsion. After extraction and phase separation by cen-trifugation, the spent sample is removed and the toluene extract iscollected and analyzed by GC–MS. Addition of surfactant enhancesdispersion of the extraction solvent in the aqueous sample andfavors the mass transfer of analytes from the aqueous sample tothe extraction solvent. This method has a total extraction time ofless than 1 min, and uses minimal surfactant as emulsifier insteadof traditional organic dispersive solvents.

In 2013, Li et al. compared the extraction droplets produced

in manual-assisted emulsification, vortex-assisted emulsifica-tion, and ultrasound-assisted extraction (USE) [49]. Micrographsof droplets show that vortex-assisted emulsification dispersedanalytes well in the emulsion, and that ultrasound-assisted

10 M.-I. Leong et al. / J. Chromatogr. A 1335 (2014) 2–14

y (a) M

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mulsification over-emulsified the mixture and resulted in incom-lete phase separation.

.1.6. Microwave-assisted emulsificationIn 2012, homogeneous ionic liquid microextraction with

icrowave-assisted emulsification was developed for the extrac-ion of active constituents from fruits of Schisandra chinensis andchisandra sphenanthera [50]. In this method, 10 mg of sampleowder, 150 �L of 1-butyl-3-methylimidazolium tetrafluoroborate[C4MIM][BF4]), and 10 mL of deionized water were combined in a

icrowave extraction vessel. After the sealed vessel was shaken,t was exposed to microwave radiation at 200 W for 6 min. Afterhe vessel is cooled to ambient temperature, 0.8 g of ammoniumexafluorophosphate ([NH4][PF6]), which is used as an ion-pairinggent, is added. A cloudy mixture is formed because of forma-

ion of fine droplets of [C4MIM][PF6] homogeneously dispersedn an emulsion. Upon formation of [C4MIM][PF6], the analytesre extracted into the IL phase. After centrifugation, the IL phaseeposits at the bottom of the centrifuge tube. This method is

SPD–DLLME and (b) D-�-SPE.

suitable for the extraction of active constituents in natural prod-ucts.

2.2. Combination of techniques for extraction and analysis withDLLME

2.2.1. Solid-phase extraction combined with DLLMESPE and DLLME coupled with GC were used for determination of

13 OPPs in aqueous samples [51]. The analytes were collected fromlarge volumes of aqueous solutions (100 mL) into the sorbent SPEC18 (100 mg). The C18 SPE cartridge was used in separation of thedesired compounds by elution with 1 mL of acetone. Eluates werecollected into a 10 mL screw-cap glass test tube. Chlorobenzene(12 �L) was added to the test tube and the resulting mixture wasdrawn into a syringe and rapidly injected into double distilled water

in a screw-cap glass test tube with conical bottom. The mixture wasthen centrifuged and the extractant was injected into the GC foranalysis. This method is fast and simple, and affords very high EFsand short analysis time.

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.2.2. Stir bar sorptive extraction (SBSE) combined with DLLMESBSE combined with DLLME [52] has been developed for the

xtraction of six triazole pesticides in aqueous samples. In thisethod, 100 mL of standard or sample solution is stirred with a

tir bar coated with octadecyl silane for 30 min at 300 rpm. The stirar is subsequently removed and placed in a 1.5 mL glass vial con-aining 1 mL of methanol for liquid desorption. After the stir bar isemoved, 25 �L of the extraction solvent 1,1,2,2-tetrachloroethanes added to the extracted analytes. The resulting solution is rapidlynjected into 5 mL of sodium chloride solution by syringe and thenentrifuged. The sedimented organic phase is removed and injectednto GC for analysis. This method enables simple, selective, andensitive determination of analytes in complex matrixes.

.2.3. Molecularly imprinted matrix solid-phase dispersionombined with DLLME (MIM–MSPD–DLLME)

A MIM synthesized by aqueous suspension polymerization waspplied as a selective sorbent for the simultaneous determinationf four Sudan dyes in egg yolk samples (Fig. 5(a)) [53]. The sor-ent was a miniaturized matrix solid-phase dispersion used forSPD–DLLME. The miniaturized MSPD procedure was performed

y using small amounts of sample, support, and solvent. An aliquotf the egg yolk sample and MIM sorbent were placed in a smalllass beaker and blended together. The homogenized mixture wasransferred to an empty cartridge (5 cm × 8 mm i.d., prepacked with0 mg of MIM), rinsed with 4.0 mL of methanol–water solution, andhen eluted with 3.0 mL of acetone–acetic acid solution. The elu-te was collected in a 10 mL conical tube and then evaporated to.0 mL. It was then mixed with 100 �L of TCE and 5.0 mL of water forurther purification and concentration of analytes by DLLME. This

IM–MSPD–DLLME method combined the advantages of MIM,SPD, and DLLME.

.2.4. Supercritical fluid extraction (SFE) combined with DLLMESFE followed by DLLME [54,55] has been developed for extrac-

ion and determination of PAHs in marine sediments. SFE of PAHsas performed at 313 K and 253.2 bar, and the extracted PAHs were

ollected in 1 mL of acetonitrile. Subsequently, 16 �L of the extrac-ion solvent chlorobenzene was added to the collecting solvent1.0 mL of acetonitrile). The resulting mixture was rapidly injectednto 5.0 mL of aqueous solution. After centrifugation, the PAHs inhe sedimented phase were analyzed by GC. This procedure extendshe application of DLLME to solid samples. In particular, it holdsreat potential in the analysis of trace organic compounds in solidamples.

.2.5. Nanotechniques combined with DLLMEDispersive micro-solid-phase extraction (D-�-SPE) (Fig. 5(b))

ombined with DLLME [56,57] was developed for GC–MS of PAHsn environmental samples. For the dispersion step, 1-octanol isnjected rapidly into a vial containing sample solution and theial is subsequently sealed and vortexed. For SPE step (absorptionnd elution), derivatized magnetic nanoparticles are then quicklydded to the vial. In this approach, hydrophobic magnetic nanopar-icles are used to recover the extractant 1-octanol in the DLLMEtep. A magnet is held next to the bottom of the vial to attractnd isolate the nanoparticles, and the sample solution is discardedy decantation. The magnet is thereafter removed, and 100 �L ofcetonitrile is introduced to the vial to desorb the 1-octanol fromhe nanoparticles by sonication. Finally, the magnet is again placedext to the vial, and the supernatant is collected into an Eppen-

orf tube by an automatic pipettor for analysis. This procedure doesot require special apparatus such as conical-bottom test tubes asell as tedious procedures of centrifugation and refrigeration of

he solvent. It also potentially lends itself to possible automation.

gr. A 1335 (2014) 2–14 11

Recently, a simple and efficient two-step method, vortex-assisted micro-solid-phase extraction (VA-�-SPE) followed bydispersive liquid–liquid microextraction based on low-densitysolvent (LDS-DLLME), was developed for the determination oftrace-level phthalate esters in environmental water samples [58].Each �-SPE device was fabricated by packing 4 mg of multiwalledcarbon nanotubes in a 1.0 cm × 0.8 cm porous polypropylene mem-brane with heat-sealed edges. In the first step of VA-�-SPE, the�-SPE device is placed in a 20 mL sample solution, which is thenvortexed for 6 min. After extraction, the �-SPE device is removedand placed in a glass insert. Analytes are desorbed by sonication for5 min and acetonitrile (350 �L) is used as dispersing solvent in thenext extraction (DLLME) step. In LDS-DLLME, a mixture of extrac-tion solvent and acetonitrile extract is rapidly injected into a 5 mL10% NaCl solution by plastic Pasteur pipette to form an emulsion.After extraction, the emulsion is separated into two phases by cen-trifugation. The organic extract is conveniently collected by usinga 50 �L microsyringe, and the extract is injected into the GC–MSsystem for analysis.

A novel and highly efficient microextraction methodology basedon the use of palladium nanoparticles was developed for thepreconcentration and determination of Hg and other inorganic ana-lytes in water samples [59]. Analytes were selectively separatedin LLME by application of clusters protected by a monolayer ofdodecanethiolate-coated Pd (C12S Pd MPCs). A 20 �L portion ofthe toluene phase containing C12S Pd MPCs was used for extrac-tion, and the final phase was injected into an electrothermal atomicabsorption spectrometer for Hg detection.

2.3. Other methods using low-toxicity solvent

At present, the development of extraction methods includes theuse of room-temperature ILs and surfactants. ILs are generally com-posed of organic cations and inorganic anions [60–63]. Comparedwith conventional organic extraction solvents, ILs have low vaporpressure, high viscosity, good thermal stability, tunable miscibilityand polarity, and good extractability with various organic and inor-ganic compounds [63,64]. Therefore, application of ILs in DLLMEto determine many various types of contaminants and pesticidesin environmental water samples have been reported [57–75]. Kuet al. used an up-and-down shaker and ILs to extract analytes whilereducing levels of extracted ILs and the use of disperser solvent[25].

Last year, flotation-assisted homogeneous liquid–liquidmicroextraction (FA-HLLME) followed by GC–FID analysis wasdeveloped for the extraction of four PAHs in soil samples [76]. Inthis method, PAHs are extracted from soil samples into methanoland water (1:1, v/v) by using ultrasound, and filtration is sub-sequent done as a cleanup step. The filtrate is added into anextraction cell, which contains a mixture of 1.0 mL of methanol(homogenous solvent) and 150.0 �L of toluene (extraction sol-vent). Through N2 flotation, the dispersed extraction solvent istransferred to the surface of the mixture and then collected bymicrosyringe. Subsequently, 2 �L of the collected organic phaseis injected into the GC–FID system for subsequent analysis. Thisnew procedure is different from the conventional homogeneousliquid–liquid microextraction (HLLE) (Fig. 4(c)), as it does not needcentrifugation to separate the organic phase. In this method, N2flotation is used to break up the emulsion of organic solvent inwater and to finish the extraction process.

Another new method, vortex-assisted supramolecularsolvent microextraction, has been developed for determina-

tion of bisphenol-A, 2,4-dichlorophenol, bisphenol-AF, andtetrabromobisphenol-A in liquid foods and their packaging mate-rials [49]. Here, a supramolecular solvent is prepared by mixing2 mL of octylalcohol and 10 mL of tetrahydrofuran in 38 mL of

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istilled water and 10 �L of HCl (2 M). After the sample prepara-ion, 500 �L of the supramolecular solvent as extraction solvents added into the sample, the mixture is vortexed for 2 min. Afterentrifugation, the supramolecular solvent, which is less densehan water, forms the top layer of the mixture. It is then removednd diluted to 1.0 mL with acetonitrile, 10.0 �L of the solution isnalyzed by HPLC.

. DLLME applications

DLLME is simple, rapid, and inexpensive, requires low volumesf sample, and affords high EF. It can be applied in the analysis ofrganic compounds (pesticides, pharmaceuticals, and phenols) andnorganic analytes (Cu, Pb, and Cd). DLLME methods have been usedn the analysis of various samples such water samples, food, urine,nimal tissue or offal, soil, and leaves. DLLME is a popular sampleretreatment step in methods developed for analysis of food.

.1. Application of DLLME for various analytes

.1.1. Organic compoundsAfter DLLME has been introduced by Rezaee et al. [6], it has

ften been used in the analysis of pesticides in water samplesainly because many highly toxic pesticides have low solubility

n water and high solubility in non-polar extraction solvents. Thextraction solvent must have ability to extract target analytes, lowolubility in aqueous samples, and applicability to the analyticalethod. Pesticides that are commonly analyzed upon extraction

y DLLME include OPPs [77], triazole pesticides [52], triazine herbi-ides [78], methomyl [79], heterocyclic insecticides [80], fungicides81], carbamate pesticides [82], and n-methyl carbamate pesti-ides [83]. These pesticides are extracted with toxic chlorinatedolvents. However, other pesticides have been analyzed by usingess-toxic extraction solvents in water. For example, OPPs [84] andenzoylurea pesticides have been extracted with hexadecane andC6MIM][PF6] [85], respectively. DLLME has also been applied to thenalysis of pharmaceuticals, and phenols such as chlorampheni-ol [86], clenbuterol [87], inflammatory drugs [88], lovastatin [89],uoroquinolones [90], alkylphenol [91], bisphenol and bisphenol B92], volatile phenols [93], chlorophenols [94,95], PAHs [54,56,96].esides the above compounds, other organic compounds such asame retardants and plasticizers [97–102], aromatic amines [103],nilines [104], fatty acids [105], glycyrrhizic acid [20], parabens106], and antioxidants [107]. These above applications illustratehat DLLME is suitable for use in extraction of different types ofrganic compounds.

.1.2. Inorganic compoundsDLLME has been applied to the extraction and concentration of

wide variety of organic compounds and metal ions [10], mainlyrom water samples. After pesticides, metals are the second mostommon analytes that are extracted by DLLME. DLLME has beensed in the last few years in the extraction and preconcentrationf metals for analysis [31,33,108–126]. Zgoła-Grzesıkowiak andrzeskowiak summarized the DLLME methods for the analyses ofarious metals [10]. In these methods, chelating agent is added tohe sample to extract the metal ions. Ions from the liquid phasere then extracted to the extracting solvent as a complex. Finally,ons are analyzed through appropriate techniques such as graphite

urnace atomic absorption spectrometry [112,120,121,124], induc-ively coupled plasma optical emission spectrometry [113], or FAAS122,123]. The number of published studies on inorganic analysisssisted by DLLME may increase very rapidly in the near future.

gr. A 1335 (2014) 2–14

3.2. Application of DLLME to various field samples

Before 2009, only a few papers describe the use of DLLME in theanalysis of analytes in food samples. Most of these works focuson water samples or aqueous phases [127–143]. Because of theincreased regulation for food safety, the importance of analysisfor contaminants or other harmful substances has been greatlyacknowledged. Food matrixes are notoriously complex; they con-tain components such as carbohydrates, lipids, and proteins [144].Bakar et al. used DLLME to extract vegetable oils containing phe-nolic acids into an aqueous solution [145].

Other complex analytes for which DLLME is used for extractionprior to analysis polychlorinated biphenyls in fish [102] and soil[146], polybrominated diphenyl ethers in animal tissue [147], Rhin leaves [124], Cd in beverage and cereal [119], and Al in fruit juice[148].

Sample preparation can affect the analyte concentration andthe cleanliness of the sample prior to further analysis. The num-bers of methods that use a two-step preparation have increasedin the last few years. Solid samples generally require previousextraction with a suitable solvent to make the analytes avail-able in a liquid matrix [149]. In these methods, analytes may beextracted from the food matrix with an organic solvent, by shakingor stirring [102,147,150–154], USE [155,156], SPE [81,154,156], ormicrowave-assisted extraction [157]. A second step that uses a dis-perser solvent is typically performed [81,102,147,150–157]. On theother hand, DLLME may be a cleanup step before extraction fromthe food matrix.

4. Conclusion

Many DLLME methods have been developed in recent years.DLLME is a novel microextraction technique with great potentialin sample pretreatment. This review introduces many novelDLLME techniques, disperser techniques, and new combinationswith DLLME. Advantages of these techniques include simplicityof operation, low cost, rapid extraction, and great potential. Inaddition, this review illustrates the application of dispersion LPMEmethods to allow separation and preconcentration of varioustypes of analytes and samples. The first section discusses variousless toxic solvents that are successfully used to develop newmethods, and many devices that were developed for DLLME.Other novel online DLLME techniques were reported. Some ofthe aforementioned dispersion techniques use very low vol-umes of organic solvent or no dispersion solvent. Furthermore,these techniques may also be combined with DLLME with low-density solvent and high-density solvents to develop other newmethods.

Combining other extraction methods with DLLME for analysis ofcomplex samples may be more effective and useful. Many combina-tions with DLLME have been reported, but not much is known aboutcombinations of extraction methods with DLLME with low-toxicitysolvent or dispersion LPME. This direction of the research may wellrepay investigation. The above DLLME or dispersion LPME methodshave benefits as cleanup and filtering steps to remove impuritiesof samples.

By using the new nanotechnique to assist extraction, the sur-face of nanoparticles can be modified to extract various organiccompounds and solvents. For example, specially coated nanopar-ticles and magnetic nanoparticles may be used to assist extractionand to retrieve the extraction solvent, respectively. Newly prepared

functional nanoparticle will extend the usages DLLME in variousapplications.

Apart from the combined methods, many traditional LPMEmethods with no dispersing solvent or DLLME have been reported.

omato

Amot

mcdf

C

A

Toid

R

M.-I. Leong et al. / J. Chr

mong LPME methods, these have much potential for develop-ent. Some of the conventional DLLME methods were developed to

bviate centrifugation and the use of disperser solvent or to lowerhe volume of the organic solvent used.

Finally, the current trend is moving toward simplification andiniaturization of sample preparation as well as reduction of the

ost, labor, time and quantities of organic solvents used. DLLME andispersion LPME have great prospects for these approaches in theuture.

onflict of interest

The authors declare no conflict of interest.

cknowledgments

This work was supported by the National Science Council ofaiwan (NSC 99-2113-M-007-004-MY3). We would like to expressur sincere appreciation to Professor David J. Wilson for assist-ng our research work and for assisting in editing our manuscriptsuring the last 30 years.

eferences

[1] L. Zhao, L.Y. Zhu, H.K. Lee, J. Chromatogr. A 963 (2002) 239.[2] M.B. Melwanki, W.H. Hsu, S.-D. Huang, Anal. Chim. Acta 552 (2005) 67.[3] G. Shen, H.K. Lee, Anal. Chem. 74 (2002) 648.[4] S.P. Huang, S.-D. Huang, J. Chromatogr. A 1176 (2007) 19.[5] E. Psillakis, N. Kalogerakis, J. Chromatogr. A 999 (2003) 145.[6] M. Rezaee, Y. Assadi, M.R.M. Hosseini, E. Aghaee, F. Ahmadi, S. Berijani, J.

Chromatogr. A 1116 (2006) 1.[7] P. Liang, J. Xu, Q. Li, Anal. Chim. Acta 609 (2008) 53.[8] H. Farahani, P. Norouzi, R. Dinarvand, M.R. Ganjali, J. Chromatogr. A 1172

(2007) 105.[9] L. Kocúrová, J.S. Balogh, J. Sandrejová, V. Andruch, Microchem. J. 102 (2012)

11.[10] A. Zgoła-Grzeskowiak, T. Grzeskowiak, Trends Anal. Chem. 30 (2011) 1382.[11] J.M. Kokosa, Trends Anal. Chem. 43 (2013) 2.[12] M. Asensio-Ramos, L.M. Ravelo-Pérez, M.A. González-Curbelo, J. Hernández-

Borges, J. Chromatogr. A 1218 (2011) 7415.[13] S. Dadfarnia, A.M.H. Shabani, Anal. Chim. Acta 658 (2010) 107.[14] M.R. Khalili-Zanjani, Y. Yamini, S. Shariati, J.A. Jönsson, Anal. Chim. Acta 585

(2007) 286.[15] M.R. Khalili-Zanjani, Y. Yamini, N. Yazdanfar, S. Shariati, Anal. Chim. Acta 606

(2008) 334.[16] M.I. Leong, S.-D. Huang, J. Chromatogr. A 1211 (2008) 8.[17] H. Xu, Z. Ding, L. Lv, D. Song, Y. Feng, Anal. Chim. Acta 636 (2009) 28.[18] M.R. Khalili-Zanjani, Y. Yamini, N. Yazdanfar, S. Shariati, Anal. Chim. Acta 606

(2008) 202.[19] M.A. Farajzadeh, S.E. Seyedi, M.S. Shalamzari, M. Bamorowat, J. Sep. Sci. 32

(2009) 3191.[20] P. Hashemi, S. Beyranvand, R.S. Mansur, A.R. Ghiasvand, Anal. Chim. Acta 655

(2009) 60.[21] A. Saleh, Y. Yamini, M. Faraji, M. Rezaee, M. Ghambarian, J. Chromatogr. A

1216 (2009) 6673.[22] P.-P. Zhang, Z.-G. Shi, Q.-W. Yu, Y.-Q. Feng, Talanta 83 (2011) 1711.[23] X.-Z. Hu, J.-H. Wu, Y.-Q. Feng, J. Chromatogr. A 1217 (2010) 7010.[24] Y.-S. Su, J.-F. Jen, J. Chromatogr. A 1217 (2010) 5043.[25] Y.-C. Ku, M.I. Leong, W.-T. Wang, S.-D. Huang, J. Sep. Sci. 36 (2013) 1470.[26] L. Guo, H.K. Lee, J. Chromatogr. A 1218 (2011) 5040.[27] C.-C. Chang, S.-Y. Wei, S.-D. Huang, J. Sep. Sci. 34 (2011) 837.[28] M.I. Leong, C.-C. Chang, M.-R. Fuh, S.-D. Huang, J. Chromatogr. A 1217 (2010)

5455.[29] L. Kocúrová, I.S. Balogh, J. Skrlíková, J. Posta, V. Andruch, Talanta 82 (2010)

1958.[30] A.N. Anthemidis, K.-I.G. Ioannou, Talanta 79 (2009) 86.[31] A.N. Anthemidis, K.-I.G. Ioannou, Talanta 84 (2011) 1215.[32] A.N. Anthemidis, K.-I.G. Ioannou, Anal. Chim. Acta 668 (2010) 35.[33] V. Andruch, C.C. Acebal, J. Skrlíková, H. Sklenárová, P. Solich, I.S. Balogh, F.

Billes, L. Kocúrová, Microchem. J. 100 (2012) 77.[34] W.-C. Tsai, S.-D. Huang, J. Chromatogr. A 1216 (2009) 5171.[35] M.A. Farajzadeh, M.R.A. Mogaddam, Anal. Chim. Acta 728 (2012) 31.[36] J. Regueiro, M. Llompart, C. Garcia-Jares, J.C. Garcia-Monteagudo, R. Cela, J.

Chromatogr. A 1190 (2008) 27.

[37] A.R. Fontana, R.G. Wuilloud, L.D. Martine, J.C. Altamirano, J. Chromatogr. A

1216 (2009) 147.[38] E. Yiantzia, E. Psillakis, K. Tyrovolaa, N. Kalogerakisa, Talanta 80 (2010) 2057.[39] A.R. Fontana, A.B. Camargo, J.C. Altamirano, J. Chromatogr. A 1217 (2010)

6334.

gr. A 1335 (2014) 2–14 13

[40] M.-W. Shu, M.I. Leong, M.-R. Fuh, S.-D. Huang, Analyst 137 (2012) 2143.[41] R.J. Chung, M.I. Leong, S.-D. Huang, J. Chromatogr. A 1246 (2012) 55.[42] S.-L. Lin, M.-R. Fuh, J. Chromatogr. A 1217 (2010) 3467.[43] L. Guo, H.K. Lee, J. Chromatogr. A 1243 (2012) 14.[44] L. Guo, H.K. Lee, J. Chromatogr. A 1235 (2012) 1.[45] Y.F. Zhang, H.K. Lee, J. Chromatogr. A 1252 (2012) 67.[46] Y. Li, P.-S. Chen, S.-D. Huang, J Chromatogr. A 1300 (2013) 51.[47] Y.F. Zhang, H.K. Lee, J. Chromatogr. A 1249 (2012) 25.[48] Y.F. Zhang, H.K. Lee, J. Chromatogr. A 1274 (2013) 28.[49] Y.T. Li, Y. Jiao, Y.H. Guo, Y.L. Yang, Anal. Methods 5 (2013) 5037.[50] Y. Xiao, H. Zhang, Anal. Chim. Acta 712 (2012) 78.[51] S. Samadi, H. Sereshti, Y. Assadi, J. Chromatogr. A 1219 (2012) 61.[52] M.A. Farajzadeh, D. Djozan, N. Nouri, M. Bamorowat, M.S. Shalamzari, J. Sep.

Sci. 33 (2010) 1816.[53] H. Yan, H. Wang, J. Qiao, G. Yang, J. Chromatogr. A 1218 (2011) 2182.[54] M. Rezaee, Y. Yamini, M. Moradi, A. Saleh, M. Faraji, M.H. Naeeni, J. Supercrit-

ical Fluids 55 (2010) 161.[55] M. Jowkarderis, F. Raofie, Talanta 88 (2012) 50.[56] Z.G. Shi, H.K. Lee, Anal. Chem. 82 (2010) 1540.[57] K.S. Tay, N.A. Rahmana, M.R.B. Abasa, Anal. Methods 5 (2013) 2933.[58] L. Guo, H.K. Lee, J. Chromatogr. A 1300 (2013) 24.[59] E.M. Martinisa, L.B. Escuderob, R. Salvarezzab, M.F. Calderónb, F.J. Ibanezb,

R.G. Wuilloud, Talanta 108 (2013) 46.[60] T. Ajioka, S. Oshima, N. Hirayama, Talanta 74 (2008) 903.[61] N.M.M. Mateus, L.C. Branco, N.M.T. Lourenco, C.A.M. Afonso, Green Chem. 5

(2003) 347.[62] H. Yang, Y. Gu, Y. Deng, F. Shi, Chem. Commun. 3 (2002) 274.[63] C.F. Poole, J. Chromatogr. A 1037 (2004) 49.[64] H. Zhao, S. Xia, P. Ma, J. Chem. Technol. Biotechnol. 80 (2005) 1089.[65] L. Ranjbar, Y. Yamini, A. Saleh, S. Seidi, M. Faraji, Microchim. Acta 177 (2012)

119.[66] J. López-Darias, V. Pino, J.H. Ayala, A.M. Afonso, Microchim. Acta 174 (2011)

213.[67] M.M. Parrilla Vazquez, P. Parrilla Vazquez, M. Martinez Galera, M.D. Gil Garcia,

Anal. Chim. Acta 784 (2010) 20.[68] C. Yao, T. Li, P. Twu, W.R. Pitner, J.L. Anderson, J. Chromatogr. A 1218 (2011)

1556.[69] M. Asensio-Ramos, J. Hernández-Borges, T.M. Borges-Miquel, M.Á. Rodríguez-

Delgado, J. Chromatogr. A 1218 (2011) 4808.[70] L.M. Ravelo-Pérez, J. Hernández-Borges, M. Asensio-Ramos, M.Á. Rodríguez-

Delgado, J. Chromatogr. A 1216 (2009) 7336.[71] R. Cruz-Vera, M. Lucena, S. Cárdenas, M. Valcárcel, J. Chromatogr. A 1216

(2009) 6459.[72] L.M. Ravelo-Pérez, J. Hernández-Borges, A.V. Herrera-Herrera, M.A.

Rodríguez-Delgado, Anal. Bioanal. Chem. 395 (2009) 2387.[73] E. Aguilera-Herrador, R.L. Lucena, S. Cárdenas, M. Valcárcel, Anal. Chem. 80

(2008) 793.[74] Y.F. Zhang, H.K. Lee, Anal. Chim. Acta 750 (2012) 120.[75] Y.F. Zhang, H.K. Lee, J. Chromatogr. A 1271 (2013) 56.[76] M.H. Hosseini, M. Rezaee, H.A. Mashayekhi, S. Akbarian, F. Mizani, M.R. Pour-

javid, J. Chromatogr. A 1265 (2012) 52.[77] S. Berijani, Y. Assadi, M. Anbia, M.R. Milani Hosseini, E. Aghae, J. Chromatogr.

A 1123 (2006) 1.[78] D. Nagaraju, S.-D. Huang, J. Chromatogr. A 1161 (2007) 89.[79] G. Wei, Y. Li, X. Wang, J. Sep. Sci. 30 (2007) 3262.[80] Y. Liu, E. Zhao, W. Zhu, H. Gao, Z. Zhou, J. Chromatogr. A 1216 (2009) 885.[81] R. Montes, I. Rodríguez, M. Ramil, E. Rubí, R. Cela, J. Chromatogr. A 1216 (2009)

5459.[82] S. Zhang, C. Li, S. Song, T. Feng, C. Wang, Z. Wang, Anal. Methods 2 (2010) 54.[83] X. Lin, X. Chen, X. Huo, Z. Yu, K. Bi, Q. Li, J. Sep. Sci. 34 (2011) 202.[84] M.-I. Leong, S.-D. Huang, J. Chromatogr. A 1216 (2009) 7645.[85] Q. Zhou, X. Zhang, J. Sep. Sci. 33 (2010) 3734.[86] H. Chen, J. Ying, H. Chen, J. Huang, L. Liao, Chromatographia 68 (2008) 629.[87] M.B. Melwanki, M.-R. Fuh, J. Chromatogr. A 1198–1199 (2008) 1.[88] A. Zgoła-Grzeskowiak, Chromatographia 72 (2010) 671.[89] T. Mao, B. Hao, J. He, W. Li, S. Li, Z. Yu, J. Sep. Sci. 32 (2009) 3029.[90] H. Yan, H. Wang, X. Qin, B. Liu, J. Du, J. Pharm. Biomed. Anal. 54 (2011) 53.[91] A. Zgoła-Grzeskowiak, J. Chromatogr. A 1217 (2010) 1761.[92] S.C. Cunha, J.O. Fernandes, Talanta 83 (2010) 117.[93] L. Farina, E. Boido, F. Carrau, E. Dellacassa, J. Chromatogr. A 1157 (2007) 46.[94] N. Fattahi, Y. Assadi, M.R.M. Hosseini, E.Z. Jahromi, J. Chromatogr. A 1157

(2007) 23.[95] N. Fattahi, S. Samadi, Y. Assadi, M.R.M. Hosseini, J. Chromatogr. A 1169 (2007)

63.[96] M.T. Pena, M.C. Casais, M.C. Mejuto, R. Cela, J. Chromatogr. A 1216 (2009)

6356.[97] M. García-López, I. Rodríguez, R. Cela, J. Chromatogr. A 1166 (2007) 9.[98] Y. Li, G. Wei, J. Hu, X. Liu, X. Zhao, X. Wang, Anal. Chim. Acta 615 (2008) 96.[99] Y. Li, J. Hu, X. Liu, L. Fu, X. Zhang, X. Wang, J. Sep. Sci. 31 (2008) 2371.

[100] X. Liu, J. Li, Z. Zhao, W. Zhang, K. Lin, Ch. Huang, X. Wang, J. Chromatogr. A1216 (2009) 2220.

[101] L. Dai, J. Cheng, G. Matsadiq, L. Liu, J.-K. Li, Anal. Chem. Acta 674 (2010) 201.[102] J. Hu, Y. Li, W. Zhang, H. Wang, Ch. Huang, M. Zhang, X. Wang, J. Sep. Sci. 32

(2009) 2103.[103] X. Wang, L. Fu, G. Wei, J. Hu, X. Zhao, X. Liu, Y. Li, J. Sep. Sci. 31 (2008) 2932.[104] J.S. Chiang, S.-D. Huang, Talanta 75 (2008) 70.

1 omato

4 M.-I. Leong et al. / J. Chr

[105] E. Pusvaskiene, B. Januskevic, A. Prichodka, V. Vickackaite, Chromatographia69 (2009) 271.

[106] M.A. Farajzadeh, D. Djozan, R.F. Bakhtiyari, Talanta 81 (2010) 1360.[107] M.A. Farajzadeh, M. Bahram, J.A. Jonsson, Anal. Chim. Acta 591 (2007) 69.[108] M. Rezaee, Y. Yamini, A. Khanchi, M. Faraji, A. Saleh, J. Hazard. Mater. 178

(2010) 766.[109] T. Asadollahi, S. Dadfarnia, A.M. Haji Shabani, Talanta 82 (2010) 208.[110] Y. Yamini, M. Rezaee, A. Khanchi, M. Faraji, A. Saleh, J. Chromatogr. A 1217

(2010) 2358.[111] E. Molaakbari, A. Mostafavi, D. Afzali, J. Hazard. Mater. 185 (2011) 647.[112] A. Bidari, E.Z. Jahromi, Y. Assadi, M.R.M. Hosseini, Michrochem. J. 87 (2007) 6.[113] M.H. Mallah, F. Shemirani, M.G. Maragheh, J. Radioanal. Nucl. Chem. 278

(2008) 97.[114] N.M. Najafi, H. Tavakoli, R. Alizadeh, S. Seidi, Anal. Chim. Acta 670 (2010) 18.[115] P. Liang, L. Zhang, E. Zhao, Talanta 82 (2010) 993.[116] H. Sereshti, V. Khojeh, S. Samadi, Talanta 83 (2011) 885.[117] X. Wen, Q. Yang, Z. Yan, Q. Deng, Microchem. J. 97 (2011) 249.[118] R. Khani, F. Shemirani, B. Majidi, Desalination 266 (2011) 238.[119] M.A. Farajzadeh, M. Bahram, M.R. Vardast, Clean Soil Air Water 38 (2010) 466.[120] P. Liang, H. Sang, Anal. Biochem. 380 (2008) 21.[121] M.T. Naseri, M.R.M. Hosseini, Y. Assadi, A. Kiani, Talanta 75 (2008) 56.[122] M.T. Naseri, P. Hemmatkhah, M.R.M. Hosseini, Y. Assadi, Anal. Chim. Acta 610

(2008) 135.[123] S.R. Yousefi, F. Shemirani, Anal. Chem. Acta 669 (2010) 25.[124] E.Z. Jahromi, A. Bidari, Y. Assadi, M.R.M. Hosseini, M.R. Jamali, Anal. Chim. Acta

585 (2007) 305.[125] S. Li, S. Cai, W. Hu, H. Chen, H. Liu, Spectrochim. Acta Part B 64 (2009) 666.[126] Q. Wu, Ch. Wu, Ch. Wang, X. Lu, X. Li, Z. Wang, Anal. Methods 3 (2011) 210.[127] J. Xiong, B. Hu, J. Chromatogr. A 1193 (2008) 7.[128] X. Zang, J. Wang, O. Wang, M. Wang, J. Ma, G. Xi, Z. Wang, Anal. Bioanal. Chem.

392 (2008) 749.[129] S.C. Cunha, J.O. Fernandes, M.B.P.P. Oliveira, J. Chromatogr. A 1216 (2009)

8835.[130] L. Fu, X. Liu, J. Hu, X. Zhao, H. Wang, X. Wang, Anal. Chim. Acta 632 (2009)

289.[131] Y. Wang, J. You, R. Ren, Y. Xiao, S. Gao, H. Zhang, A. Yu, J. Chromatogr. A 1217

(2010) 4241.[132] J. Du, H. Yan, D. She, B. Liu, G. Yang, Talanta 82 (2010) 698.[133] F. Qiao, X. Zhang, M. Wang, Y. Kang, Chromatographia 72 (2010) 331.

gr. A 1335 (2014) 2–14

[134] C. Jia, X. Zhu, L. Chen, M. He, P. Yu, E. Zhao, J. Sep. Sci. 33 (2010) 244.[135] S. Gao, J. You, X. Zheng, Y. Wang, R. Ren, R. Zhang, Y. Bai, H. Zhang, Talanta 82

(2010) 1371.[136] D. Moreno-González, L. Gámiz-Gracia, A.M. García-Campana, J.M. Bosque-

Sendra, Anal. Bioanal. Chem. 400 (2011) 1329.[137] X. Huo, Q. Li, X. Lin, X. Chen, K. Bi, Chromatographia 73 (2011) 313.[138] N. Campillo, P. Vinas, J.I. Cacho, R. Penalver, M. Hernández-Córdoba, J. Chro-

matogr. A 1217 (2010) 7323.[139] C. Pizarro, C. Sáenz-González, N. Pérez-del-Notario, J.M. González-Sáiz, J.

Chromatogr. A 1217 (2010) 7630.[140] C. Pizarro, C. Sáenz-González, N. Pérez-del-Notario, J.M. González-Sáiz, J.

Chromatogr. A 1218 (2011) 1576.[141] A.R. Fontana, S.H. Patil, K. Banerjee, J.C. Altamirano, J. Agric. Food Chem. 58

(2010) 4576.[142] V.P. Jofré, M.V. Assof, M.L. Fanzone, H.C. Goicoechea, L.D. Martínez, M.F. Silva,

Anal. Chim. Acta 683 (2010) 126.[143] L. Campone, A.L. Piccinelli, L. Rastrelli, Anal. Bioanal. Chem. 399 (2011) 1279.[144] http://www.sepscience.com/Sectors/Food/Articles/415-/The-Importance-of-

Sample-Preparation-in-Food-Analysis[145] N.B.A. Bakar, A. Makahleh, B. Saad, Anal. Chim. Acta 742 (2012) 59.[146] J. Hu, L. Fu, X. Zhao, X. Liu, H. Wang, X. Wang, L. Dai, Anal. Chim. Acta 640

(2009) 100.[147] X. Liu, J. Hu, Ch. Huang, H. Wang, X. Wang, J. Sep. Sci. 32 (2009) 4213.[148] H. Abdolmohammad-Zadeh, G.H. Sadeghi, Talanta 81 (2010) 778.[149] M. Asensio-Ramos, L.M. Ravelo-Pérez, M.Á. González-Curbelo, J. Hernández-

Borges, J. Chromatogr. A 1218 (2011) 7415.[150] E. Zhao, W. Zhao, L. Han, S. Jiang, Z. Zhou, J. Chromatogr. A 1175 (2007) 137.[151] S. Moinfar, M.R.M. Hosseini, J. Hazard. Mater. 169 (2009) 907.[152] W.H. Tsai, H.Y. Chuang, H.H. Chen, J.J. Huang, H.C. Chen, S.H. Cheng, T.C. Huang,

Anal. Chim. Acta 656 (2009) 56.[153] W.H. Tsai, W.C. Huang, H.H. Chen, Y.W. Wu, J.J. Huang, H.Y. Chuang, J. Chro-

matogr. A 1217 (2010) 250.[154] X. Liu, A. Zhao, A. Zhang, H. Liu, W. Xiao, C. Wang, X. Wang, J. Sep. Sci. 34

(2011) 1084.

[155] A. Bidari, M.R. Ganjali, P. Norouzi, M.R.M. Hosseini, Y. Assadi, Food Chem. 126

(2011) 1840.[156] B. Liu, H. Yan, F. Qiao, Y. Geng, J. Chromatogr. B 879 (2011) 90.[157] Y. Zhou, L. Han, J. Cheng, F. Guo, X. Zhi, H. Hu, G. Chen, Anal. Bioanal. Chem.

399 (2011) 1901.