Microextraction techniques coupled to liquid chromatography with mass spectrometry for the determination of organic micropollutants in environmental water samples

Molecules 2014, 19, 10320-10349; doi:10.3390/molecules190710320 molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Microextraction Techniques Coupled to Liquid Chromatography with Mass Spectrometry for the Determination of Organic Micropollutants in Environmental Water Samples Mª Esther Torres Padrón, Cristina Afonso-Olivares, Zoraida Sosa-Ferrera and José Juan Santana-Rodríguez * Departamento de Química, Universidad de Las Palmas de Gran Canaria, 35017, Las Palmas de Gran Canaria, Spain; E-Mails: miriam.torres@ ulpgc.es (M.E.T.-P.); cristina.afonso1[email protected] (C.A.-O.); [email protected] (Z.S.-F.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +34-928-454-425; Fax: +34-928-452-900. Received: 13 May 2014; in revised form: 2 July 2014 / Accepted: 10 July 2014 / Published: 16 July 2014 Abstract: Until recently, sample preparation was carried out using traditional techniques, such as liquid–liquid extraction (LLE), that use large volumes of organic solvents. Solid-phase extraction (SPE) uses much less solvent than LLE, although the volume can still be significant. These preparation methods are expensive, time-consuming and environmentally unfriendly. Recently, a great effort has been made to develop new analytical methodologies able to perform direct analyses using miniaturised equipment, thereby achieving high enrichment factors, minimising solvent consumption and reducing waste. These microextraction techniques improve the performance during sample preparation, particularly in complex water environmental samples, such as wastewaters, surface and ground waters, tap waters, sea and river waters. Liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) and time-of-flight mass spectrometric (TOF/MS) techniques can be used when analysing a broad range of organic micropollutants. Before separating and detecting these compounds in environmental samples, the target analytes must be extracted and pre-concentrated to make them detectable. In this work, we review the most recent applications of microextraction preparation techniques in different water environmental matrices to determine organic micropollutants: solid-phase microextraction SPME, in-tube solid-phase microextraction (IT-SPME), stir bar sorptive extraction (SBSE) and liquid-phase microextraction (LPME). Several groups of compounds are considered organic micropollutants because these are being OPEN ACCESS Molecules 2014, 19 10321 released continuously into the environment. Many of these compounds are considered emerging contaminants. These analytes are generally compounds that are not covered by the existing regulations and are now detected more frequently in different environmental compartments. Pharmaceuticals, surfactants, personal care products and other chemicals are considered micropollutants. These compounds must be monitored because, although they are detected in low concentrations, they might be harmful toward ecosystems. Keywords: organic micropollutants; water samples; pesticides; pharmaceuticals; personal care products; microextraction techniques Acronyms ACN Acetonitrile LLLME Liquid-liquid-liquid microextraction AMMWCNT-PDMS Amino-modified multi-walled carbon nanotube-PDMS LLME Liquid-liquid microextraction APEOs Alkylphenols ethoxylated LODs Limit of detections APs Alkylphenols LOQs Limit of quantifications BPA Bisphenol A LPME Liquid-phase microextraction BUVSs Benzotriazole UV stabilizers MeOH Methanol CCL Contaminant candidate list MIPs Moleculary-imprinted polymers CME Capillary microextraction MISPME Moleculary-imprinted solid phase microextraction CNPrTEOS Cyanopropyltriethoxysilane MOF Metal-organic framework CNTS Carbon nanotubes MS Mass spectrometry CW/DVB Carbowax/divinylbenzene MS/MS Tandem MS CW/TPR Carbowax/template resin MWCNTs Multi-wall carbon nanotubes DAD Diode array detector NSAIDs Non-steroidal anti-inflammatory drugs DESI-MS Desorption electrospray ionization mass spectrometry PAHs Polyciclic aromatic hydrocarbons DI-SPME Direct inmersion solid phase microextraction PCBs Polychlorinated biphenyls DLLME Dispersive liquid-liquid microextraction PCPs Personal care products DLLME-SFO DLLME based on floating organic droplet PDMS Polydimethylsiloxane DLPME Dispersive liquid phase microextraction PDMS/DVB Polydimethylsiloxane/divinibenzene DSDME Directly-suspended droplet microextraction PEG Polyethyleneglycol dSPME dual-SPME PFCs Perfluorinated compounds EDCs Endocrine disruptor compounds PFOA Perfluorooctanoic acid Molecules 2014, 19 10322 EG Ethyleneglycol PFOS Perfluorooctane sulfonate ESI Electrospray ionization PILs Polymeric ionic liquids EU European Union POP Persistent organic pollutants FD Fluorescence detector PPCPs Pharmaceuticals and personal care products FDA Food and Drug Administration PPY Polypyrrole FQs Fluoroquinolones RDSE Rotating disk sorptive extraction GC Gas chromatography SBSE Stir-bar sorptive extraction HF(2)ME Hollow-fibre-protected 2-phase microextraction SDCME Single-drop coacervative microextraction HF(3)ME Hollow-fibre-protected 3-phase microextraction SDME Single-drop microextraction HF-LPME Hollow-fibre liquid phase microextraction SME Solven microextraction HFM-LLLME Hollow membrane liquid-liquid-liquid microextraction SPE Solid phase extraction HF-SLPME Hollow fibre solid-liquid phase microextraction SPME Solid phase microextraction HPLC High performance liquid chromatography SWCNTs Single-wall carbon nanotubes HS-SDME Headspace single-drop microextraction TFME Thin-film microextraction HS-SPME Headspace solid phase microextraction TF-SPME Thin-film solid phase microextraction ICP-MS Inductively coupled plasma-mass spectrometry TOF/MS Time-of-flight mass spectrometry IL-DLLME Ionic liquid-dispersive liquid-liquid microextraction UHPLC Ultra high performance liquid chromatography IL-DLPME Ionic liquid dispersive liquid-phase microextraction UHPLC-MS Ultra high performance liquid chromatography mass spectrometry ILs Ionic liquids UHPLC-MS/MS Ultra high performance liquid chromatography tandem mass spectrometry IT-SPME In-tube solid phase microextraction USEPA US Environmental Protection Agency LC-MS Liquid chromatography-mass spectrometry US-IL-DLLME Ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction LC-MS/MS Liquid chromatography tandem mass spectrometry VALLME Vortex-Assisted liquid–liquid Microextraction WFD Water Framework Directive LLE Liquid-liquid extraction WWTP Wastewater treatment plant Molecules 2014, 19 10323 1. Introduction The most representative chromatographic procedures for analysing micropollutants in water samples are based on multiresidue analysis with gas chromatography (GC). This instrumental technique requires volatile, thermally stable compounds, and many of the substances of interest in environmental samples tend to be adsorbed and decomposed on the columns or injector. Therefore, derivatisation reactions must be used [1]. Liquid chromatography (LC) and ultra-high-performance liquid chromatography (UHPLC) are now being used in combination with mass spectrometry (MS) for target analytes and for identifying nontarget analytes that are highly polar and non-volatile and have high molecular weights, making them incompatible with GC. Consequently, both the targeted and non-targeted analytes can be analysed or identified within a single analytical run. Therefore, liquid chromatography-mass spectrometry (LC-MS) combined with a sample pre-concentration/clean-up step is employed due to its excellent sensitivity and selectivity [2]. Sample treatment and enrichment processes are crucial during environmental analyses because the concentrations typically found in environmental waters are very low and the matrices are highly complex. Sample preparation may include clean-up and pre-concentration procedures to ensure that the analytes are found at a suitable concentration level. Liquid-liquid extraction (LLE) and solid-phase extraction (SPE) are exhaustive traditional preparation techniques used to extract and pre-concentrate different families of analytes from environmental water samples. The need to reduce solvent volumes and to avoid using toxic organic solvents during LLE and SPE has led to adaptations of existing sample-preparation methods toward the development of new approaches. Consequently, miniaturisation has become a key factor while pursuing these objectives, and new techniques have been developed. Microextraction techniques are generally defined as non-exhaustive sample preparation methods that utilise a very small volume of the extracting phase (in the range of µL) relative to the sample volume. Analytes are extracted using a small volume of a solid or semi-solid polymeric material through solid-phase microextraction (SPME) or of a liquid through solvent microextraction (SME). Despite the substantial structural differences between both techniques, they share similar features because they are both microextraction approaches [3]. Both methods are useful alternatives for sample preparation due to their simplicity, effectiveness, low cost, minimal solvent use and excellent abilities to clean up samples. In this work, we review some of the most commonly used microextraction techniques and their applications toward the determination of some families of micropollutants in environmental liquid samples using mainly LC-MS. Until the mid-1990s, the organic trace analysis of water mainly focused on persistent organic pollutants (POP), such as polychlorinated biphenyls (PCBs), polyciclic aromatic hydrocarbons (PAHs), organochlorine pesticides, etc., based on their physicochemical characteristics (hydrophobicity, bioaccumulation and biomagnification through the trophic aquatic chain). Most of these substances have been banned, and their environmental concentrations are strictly controlled. However, interest in the fate and role of organic micropollutants, which they are present in the aqueous environment in nanograms or micrograms per litre, has increased. Many of these compounds are employed as Molecules 2014, 19 10324 household chemicals. Several pharmaceutical drugs, disinfection agents, pesticides and different personal care products can be included in this group [4], and these chemicals are also called emerging contaminants. This term refers to compounds that were not considered or known to be significant in terms of distribution and/or concentration in the past but are now widely detected [5]. Micropollutants include substances such as pharmaceuticals, drugs of abuse, biocidal compounds, food additives, cosmetic ingredients or detergents [6]. These compounds are often released from various municipal, agricultural and industrial sources and pathways and have been detected in wastewater treatment plant (WWTP) effluents [7–10]. Moreover, increasing evidence suggests that many organic micropollutants are endocrine disruptor compounds (EDCs) found in various products, including plastic bottles, detergents, flame-retardants, food, toys, cosmetics, pesticides, etc. These organic micropollutants and their degradation products may be toxic and persistent and, despite being detected in low concentrations, could produce potentially harmful effects on ecosystems and human health [11,12]. The US Environmental Protection Agency (USEPA) published the final Contaminant Candidate List (CCL-3) in September 2009, which is a drinking-water priority-contaminant list used for regulatory decision-making and information collection. The contaminants listed are either known or anticipated to exist in drinking-water systems and will be considered for regulation. This final CCL-3 contains 104 chemicals and 12 microbial contaminants, including pesticides, disinfection by-products, chemicals used in commerce, waterborne pathogens, pharmaceuticals and biological toxins [13]. Similarly, the Water Framework Directive (WFD) sets the European Union (EU) strategy against the pollution of water by dangerous substances. The WFD provisions will require the Member and Associated States to establish programs to monitor water quality, review the effect of human activity on pollutants and perform an economic analysis of water use. In this context, an initial list of priority substances was published in 2001. This list was revised in 2008, coinciding with Directive 2008/105/EC; the latter document was related to the environmental quality standards in the field of water policy. A new list was published in 2011 [14]. In the future, some of these organic micropollutants might be candidates for introduction into the WFD list of priority substances. 2. Solid-Phase Microextraction Arthur and Pawliszyn [15] introduced solid-phase microextraction (SPME), generating interest in microextraction techniques for analytical chemistry. When using SPME, the analytes are isolated based on the equilibrium between the sample matrix and the extractive coating after selecting an appropriate extractive phase and reducing the volume to remove as many of the unwanted compounds as possible. This strategy leads to efficient clean-up and minimizes the matrix effect during mass spectrometry detection, which is a serious concern in liquid LC–MS systems. SPME configurations can be classified into static and dynamic techniques. Static procedures are typically carried out in stirred samples, including fibre SPME, thin-film microextraction (TFME), rotating disk sorptive extraction (RDSE), stir bar sorptive extraction (SBSE) and dispersive SPME. Fibre SPME, which is the most common format for this technique, utilises a sorbent coating on the outer surface of a fused silica fibre to extract the analyte(s) from the sample matrix; this process occurs through direct immersion (DI-SPME) or from the sample headspace in a closed container (HS-SPME). The dynamic techniques include capillary microextraction (CME) techniques, such as in-tube SPME Molecules 2014, 19 10325 (IT-SPME), in-needle and in-tip microextraction configurations. SPME focuses mainly on the development of new coatings and novel analytical strategies that improve the sensitivity [16]. A schematic diagram of some configurations is shown in Figure 1. Figure 1. Scheme of some solid phase microextraction techniques. Sol-gel technology was applied to prepare SPME fibres in 1997 [17]; since then, it has become one of the most popular approaches for preparing novel SPME coatings. This technology has already helped synthesise many novel sorbents for SPME with large surface areas, unique selectivity and high thermal and solvent stabilities; these characteristics contribute to the high sample pre-concentration factors. The versatility of these materials enables the creation of surface-bonded sorbent coatings on unbreakable fibre materials and on substrates with different geometrical formats. Sol-gel coatings are applied during the extraction of various analytes from different sample matrices in the fibre-SPME and in the SBSE configuration [18]. Therefore, a novel polar sol-gel precursor, cyanopropyltriethoxysilane (CNPrTEOS), was combined with PDMS for the SBSE of two non-steroidal anti-inflammatory drugs (NSAIDs) from aqueous samples [19]. Molecules 2014, 19 10326 Carbon nanotubes (CNTs) are interesting targets when studying new materials in SPME. CNTs are allotropic forms of graphitic carbon comprising a single rolled graphite lamella that forms a tube (single-wall carbon nanotubes, SWCNTs) or several single tubes arranged around a common axis (multi-wall carbon nanotubes, MWCNTs); the surface-to-volume ratios of these materials are significant [20,21]. A sol-gel amino-modified multi-walled carbon nanotube-PDMS (AMMWCNT-PDMS) was synthesised for use as a novel coating for the SBSE of phenols from environmental waters [22]. Metal-organic frameworks (MOF) are a new class of porous solid materials that are self-assembled by metal ions and organic ligands. Recently, Hu et al. [23] proposed a sol-gel coating for SBSE based on PDMS and a MOF to analyse oestrogens in environmental water samples. The selectivity required for SPME can be provided through molecular imprinting (MIPs), as demonstrated by Koster et al. [24]. MIPs are polymeric materials with a high binding capacity and good selectivity against a target molecule purposely introduced during the synthetic process. MIPs are typically synthesised through the co-polymerisation of functional monomers and templates. The functional monomers should possess specific functional groups, and the templates are always the target analytes or their analogous compounds. Cross-linkers are also required to form rigid polymer networks that stabilise the cavities for the target molecules, making the polymer mechanically and thermally robust. Porogens are sometimes required to attain a porous morphology and thereby enhancing mass transfer [25]. A new polymerisation strategy called molecular imprinting solid-phase microextraction (MISPME) has been developed in different formats, such as MIP-coated fibres (polymeric membranes) and MIP rod-like fibres (polymeric monoliths). MISPME is a successful and novel microextraction technique that enriches the selected analytes from various real samples, including environmental samples [26]. Bisphenol A [27], phthalates [28] and triazines [29] in liquid samples have been detected through this strategy. Ionic liquids/polymeric ionic liquids (ILs/PILs) are promising sorbent-coating materials designed to exhibit high selectivity for targeted analytes. ILs are salts with organic cations and organic/inorganic anions with melting points at or below 100 °C. These materials possess high thermal stability, tuneable viscosity and solvation capabilities and negligible vapour pressures. The primary advantage of using ILs as SPME sorbent coatings involves the ability to incorporate various substituents into the IL structure [30]. PILs are polymers synthesised from IL monomers that exhibit some advantages over ILs when used as coatings for SPME. PILs often possess higher viscosities and greater mechanical strengths compared to ILs but exhibit similar extraction selectivities [30]. Although studies of IL/PILs-based sorbent coatings in SPME have become extremely popular, the stability must be improved to enhance the robustness of the coating when studying new sorbent-loading methodologies and fibre surface modifications. Both ILs and PILs have been widely used as SPME coatings in numerous applications, especially for the analysis of water samples, through both direct immersion and headspace; all of these methods have been coupled to GC [30]. In-tube SPME, which is the capillary format of SPME, utilises a tubular extraction device that contains an extraction phase as a surface coating or monolithic sorbent bed. In-tube SPME is also known as capillary microextraction (CME) [18]. In this case, the sorbent medium plays the most significant role during sample preparation; it is highly selective for the target analyte and should be thermally and chemically stable, providing highly efficient extraction. Unlike SPME fibres, the coated capillaries are not commercially available. Toward that purpose, a small selection of commercially Molecules 2014, 19 10327 available GC columns is used [31]. Aufartová et al. [32] optimised this microextraction technique to extract oestrogens from environmental liquid samples using Carboxen and Supel-Q capillary columns. However, the low sorbent loading, which resulted from the thin stationary phase coatings in the used GC column segments, results in low sample capacity, impeding the pre-concentration step. In the last decade, sol-gel coatings and monolithic beds have been developed to solve the in-tube SPME problems (e.g., low sorbent loading) in order to overcome this format-related deficiency [18]. Micellar media have been used as alternatives to organic solvent during IT-SPME [33]. Similarly to SPME, stir bar sorptive extraction (SBSE) is also an equilibrium-based non-exhaustive sample-preparation technique. However, the major difference between SPME and SBSE is the high sorbent loading on the stir bars, which imparts increased sample pre-concentration capabilities. During stir bar sorptive extraction (SBSE), a magnetic stir bar coated with polydimethylsiloxane (PDMS), which has a larger surface area than a SPME fibre, is spun into an aqueous sample (or extract) for a selected long extraction time. Once the extraction step is completed, the stir bar is removed, a step that is usually performed manually, and a fraction of the concentrated extract is transferred to a GC system or diluted for LC analysis [34]. The feasibility of SBSE for pre-concentrating analytes with medium to low polarity and divergent volatility from essentially aqueous samples (or extracts) has been demonstrated [35–37], and the several advantages of SBSE compared to SPME in most of these applications have been described. However, this technique has not been as widely accepted as SPME due to the limited number of commercially available coatings and the difficulty of achieving full automation. Currently, efforts in this field are focused on the development of dual phase/hybrid twisters, where the conventional PDMS phase is combined with another sorbent to increase the selectivity and/or efficiency of the extraction process [19], or alternative new coating materials with improved analytical features, promoting the retention of polar compounds from complex matrices. An extensive review published by Gilart et al. [38] covers the state of novel commercial and in-house coatings for SBSE in recent years, particularly their application for the extraction of polar micropollutants from complex matrices. Bar adsorptive micro-extraction (BAµE) is a novel static microextraction technique for trace analysis of polar compounds in aqueous media, which uses nanostructured materials (e.g., activated carbons or polymers), for each particular type of target compounds [39]. This new analytical approach, operates under the floating sampling technology and it has shown high effectiveness in many applications [40–42]. The major trends in SPME are moving toward the introduction of new selective coatings and devices to enhance the extraction efficiencies from complex matrices. 3. Solvent Microextraction Solvent microextraction (SME) is a technique for sample preparation involving the extraction and concentration of liquid, gaseous and solid samples with solvent volumes in the µL or sub-µL range, thereby enabling high enrichment factors. The term liquid-phase microextraction (LPME) is also frequently used to describe this process [43]. This rapid inexpensive preparation technique uses minimal solvent volumes with negligible exposure to toxic organic solvents. LPME is normally performed using a small volume of a water-immiscible solvent and an aqueous phase containing the analytes of interest. From the introduction of the first paper on SME in 1996 [44] until now, different Molecules 2014, 19 10328 approaches have been developed in two broad categories: exposed solvent and membrane-protected solvent [45]. Exposed solvent techniques include single-drop microextraction (SDME), headspace single drop microextraction (HS-SDME), liquid-liquid microextraction (LLME, which is also called directly suspended droplet microextraction, DSDME), liquid-liquid-liquid microextraction (LLLME) and dispersive liquid-liquid microextraction (DLLME) [43,45] as shown as in Figure 2. Figure 2. Scheme of some solvent microextraction techniques. Single Drop Microextraction (SDME) is a miniature liquid-liquid extraction: a drop of water immiscible organic extracting solvent (approximately 1–10 µL) is suspended from a syringe into the liquid or gaseous sample medium. After extraction, the liquid extractant is drawn back into the microsyringe and used directly to determine the analytes via GC. SDME is not exhaustive, and only a small fraction of the analyte is extracted and pre-concentrated for analysis [43]. Headspace (HS-SDME) enables the extraction and pre-concentration of volatile or semi-volatile compounds into a microdrop exposed to the headspace above the sample. The drop remains at the tip of the microsyringe throughout the extraction period before being retracted back into the microsyringe. In this mode, the analytes are distributed between three phases: the water sample, headspace and organic drop. HS-SDME can achieve a high degree of extract clean-up because non-volatile compounds and high-molecular-weight species are not extracted [43,45]. In all cases, GC is used to determine the target analytes. The major disadvantages of both techniques are the susceptibility of the drop toward dislodging during sampling, the size limitations of the drop and the volatility of the extraction solvent [45]. To resolve these drawbacks, air is deliberately introduced with the solvent drop, leading to a larger solvent surface area. The bubble also tends to support high-density solvents (e.g., CHCl3), which tend Molecules 2014, 19 10335 Although there are many extraction techniques for liquid samples, solid-phase extraction is the most common. Other miniaturisation techniques have also been employed to analyse hormones in water samples: SPME, IT-SPME, DLLME and SBSE [84]. However, LC coupled with DAD or a fluorescence detector (FD) was used for detection; a unique study employing microextraction techniques coupled to LC-MS was published by Mitani et al. [85] (Table 3). Five oestrogens were analysed in environmental waters by IT-SPME with a Supel-Q PLOT capillary column. The recoveries under the optimal conditions ranged from 86.1% to 106.8%, and the LOD ranged from 2.7 to 11.7 ng·L−1. 4.6. Pharmaceuticals The presence of pharmaceutical compounds in aquatic media is a challenge during environmental monitoring. These substances are pervasive in rivers, lakes and oceans due to their dispersion through wastewater [86]. Although many countries use advanced technologies, such as ozonation, reverse osmosis, and granular active carbon, to treat potable water, some compounds resist treatment [87]. Despite the existence of numerous pharmaceutical compounds, few studies utilised liquid chromatography with mass spectrometric detection (LC-MS) with microextraction techniques, as shown in Table 3. Two studies have used SPME to extract similar antibiotics compounds in liquid samples. Balakrishnan et al. [88] used Carbowax/divinylbenzene (CW/DVB) fibres to extract ten sulphonamide antibiotics from different wastewater samples, revealing a viable method for overcoming the matrix effects. McClure et al. [89] optimised a SPME method using Carbowax-template resin (CW/TPR) fibres to collect antibiotics (five of nine compounds were sulphonamides) in influent and effluent samples simultaneously. The LODs obtained in this study were better (ng·L−1) than those obtained by Balakrishnan et al. [88]. A multi-residue analysis of the pharmaceutical compounds in wastewater through dual solid-phase microextraction (dSPME) was realised by Unceta et al. [90]. Two CW/TPR fibres with different pH values were used to obtain excellent recoveries (89.2%–109.7%) for numerous compounds. Strittmatter et al. [91] developed an analytical method by combining C18/SCX mixed thin-film microextraction (TFME) and desorption electrospray ionisation mass spectrometry (DESI-MS) to determine pharmaceuticals in aqueous samples. Combining both techniques improves the analysis time considerably compared to traditional liquid chromatography mass spectrometry (LC-MS). The results were compared, and good agreement was found through a concentration range spanning three orders of magnitude. Serious matrix effects were observed in treated wastewater, but the lower limits of detection were still in the low ng·L−1 range. IT-SPME was used by Mitani et al. [92] to extract five fluoroquinolones (FQs) from environmental waters using a fully automated method with a Carboxen 1010 PLOT capillary column-like IT-SPME system coupled to a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The extracted compounds were easily desorbed using the mobile phase. The LODs of the five FQs ranged from 7 to 29 ng·L−1. The IT-SPME method had between 60-94-fold higher sensitivity than the direct injection method. Ohcho et al. developed an IT-SPME method using a Carboxen 1006 PLOT capillary column to simultaneously determine 15 non-steroidal anti-inflammatory drugs (NSAIDs) in environmental Molecules 2014, 19 10336 water [93]. The LODs of the NSAIDs ranged from 5 to 65 ng·L−1. This method could be used to analyse surface and wastewater samples without any pre-treatment or interference peaks. Although IT-SPME has achieved good recoveries (above 80%) and limits of detection (ng·L−1) for the analysed compounds, it is rarely used with LC-MS detection. In recent years, stir bar solid extraction (SBSE) has been used to determine different pharmaceutical compounds. SBSE with different commercial external coatings, such as PDMS (polydimethylsiloxane), EG Silicone (ethylene glycol-silicone) and PA (acrylate), can be used [72]. Moreover, new SBSE coatings have been prepared. In this context, Bratkowska et al. [94] synthesised and evaluated a monolithic and hydrophilic stir bar coating based on a methacrylic acid and divinylbenzene copolymer [poly(MAA-co-DVB)] for the SBSE of polar pharmaceuticals from complex environmental water samples. The extraction performance of the synthesised stir bar was compared to the extraction performance of a commercially available polydimethylsiloxane stir bar. The former produced significantly higher extraction efficiencies for polar analytes (% recovery values near 100% for most of the studied analytes) than the commercial product. The LODs of the developed method were 10 ng·L−1 for most of the target compounds, with the exception of naproxen (50 ng·L−1). Similarly, the same authors [95] prepared a stir bar coated with a hydrophilic polymer based on poly(N-vinylpyrrolidone-co-divinylbenzene) for the sorptive extraction of polar pharmaceuticals from environmental water matrices, including river, effluent and influent waste water, followed by liquid desorption and subsequent LC-MS/MS. The LODs were between 10 and 50 ng·L−1. Finally, a new polar monolith based on poly(poly(ethylene glycol) methacrylate-co-pentaerythritol triacrylate) (poly(PEGMA-co-PETRA)) was synthesised by Gilart et al. [96] and applied as a coating for stir bar sorptive extraction (SBSE) to determine a group of pharmaceuticals from environmental water samples. The coating could extract and desorb most of the studied analytes more effectively and rapidly than the recently commercialised polar stir bars. The analytical methodology was validated with LODs between 15 and 50 ng·L−1. Martin et al. [97] compared SBSE and DLLME methods; both techniques were used with acetone as the dispersant and chlorobenzene as the extractant solvent to analyse statin drugs in different environmental water samples. DLLME generated better results than SBSE because SBSE only extracted two of the six pharmaceuticals. The DLLME recoveries approached 92%. Different researchers have used DLLME to determine pharmaceutical compounds with LC-MS. Parrilla et al. [98] developed an ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction (US-IL-DLLME) procedure for the extraction of nine pharmaceuticals from wastewater samples. The US process accelerated the formation of a fine cloudy solution containing an ionic liquid (IL), specifically 1-octyl-3-methylimidazolium hexafluorophosphate ([C8MIM][PF6]), and acetonitrile (ACN) as the extractant and dispersant, respectively. Moreover, the recoveries of the pharmaceuticals increased when an ice-water bath extraction was included during the analytical procedure. The LODs for the extraction of the target analytes from wastewater samples ranged from 0.2 to 60 ng·L−1 with recoveries between 88% and 111%. Molecules 2014, 19 10337 Table 1. Microextraction techniques to determine pesticides in environmental water samples by liquid chromatography-tandem mass spectrometry. Compounds Matrix Extraction Technique Optimal Times Handling Recovery Accuracy (%) LOD (ng·L−1) Ref. Organic tin compounds (trimethyltin chloride, tripropyltin chloride, tri-phenyltin hydroxide, tributyltin chloride) Freshwater and seawater SPME Extraction: 45 min Desorption: 5 min Easy to use 71–104 6–185 [59] Benzylic and aliphatic quaternary ammonium compounds Tap water and surface water SPME Extraction: 45 min Desorption: 15 min 96 well system 97–143 10–500 [60] Polar pesticides (diuron, fluometuron, linuron, monuron, neburon, siduron, barban, carbaryl, chlorpropham, methiocarb, promecarb, propham) Tap water, surface water and well water. IT-SPME 15 draw/eject cycle 12 min Lower handling 77–104 10–1200 [61] Multiresidue (atrazine, chlorfenvinphos, chlorpyriphos, di(2-ethylhexyl)phthalate, diuron, isoproturon, simazine, terbuthylazine, trifluralin) Wastewater, superficial and coastal water IT-SPME 18 min Lower handling 8–166 25–2500 [62] Pesticides (alachlor, buprofezin, chlorpyriphos, chlorfenvinphos, diuron, fenthion, hexythiazox, isoproturon, malathion, tolclofos methyl, prochlora, imazalil, abamectin, diazinon, atrazine, simazine) Surface water SBSE Extraction: 60 min Desorption: 30 min Practical 3–62 10–1000 [63] Antimicrobial compounds (triclosan, triclocarban) River water and wastewater SBSE Extraction: 180 min Desorption: 15 min Practical 25–89 2.5–10 [64] Pesticides (carbofuran, clomazone, tebuconazole) Tap water DLLME Extraction: seconds Fast. Ease of operation 62.7–120 20 [65] Triclosan and 2,4-dichlorophenol Tap water and surface water DLLMESFO Extraction: 1 min Easy extraction-solidification 83–119 2–20 [66] Triazine herbicides (cyanazine, simazine, atrazine) Wastewater, river water underground water and drainage water IL-DLPME Extraction: 30 min Centrifugation: 15 min Simple 85.1–100 50–60 [67] Triclosan and triclocarban Wastewater and tap water IL-DLPME Extraction: short time Centrifugation: 10 min Simple 70.0–103.5 40–580 [68] Molecules 2014, 19 10338 Table 2. Microextraction techniques to determine UV filters, alkyphenols, bisphenol A and PFCs in environmental water samples by liquid chromatography-tandem mass spectrometry. Compounds Matrix Extraction Technique Optimal Times Handling Recovery Accuracy (%) LOD (ng·L−1) Ref. UV filters (2,2-dihydroxy-4-methoxybenzophenone, benzophenone-3, octocrylene, and octyldimethylp-aminobenzoic acid) River water and wastewater SBSE Extraction: 180 min Desorption: 15 min Practical 25–89 5–10 [64] Benzotriazole UV stabilizers (UV P, UV 329, UV 326, UV 328, UV 327, UV 571, UV 360) Seawater and wastewater SBSE Extraction: 120 min Desorption: 20 min Practical 68.4–92.2 18.4–55.1 [71] Personal care products (benzotriazole, 2,4-dihydroxybenzophenona, benzylparaben, 2,4-dihydroxy-4-methoxybenzophenone, benzophenone-3) Wastewater SBSE Extraction: 240 min Desorption: 15 min (60 min for PA) Optimal times depend on coatings <1–80 5.0–10.0 [72] BPA, APs Seawater DLLME Extraction: 5 min Centrifugation: 3 min Without any dispersant agent simplifies the process 84–104 5–30 (LOQ) [74] APs Wastewater HF-LPME Extraction: 30 min 97–109 100 (LOQ) [75] PFOS and PFOA Surface water and wastewater IT-SPME 25 min Lower handling 40 samples/day 81.1–85.4 1.5–3.2 [80] PFOS and PFOA River water SPME Extraction: 60 min Desorption: 15 min 88–120 2.5–7.5 [81] PFOS Tap, river and well water VALLME Extraction: 2 min Centrifugation: 2 min Not require the use of certain sample preparation apparatus 90.8–105.1 1.6 [82] Molecules 2014, 19 10339 Table 3. Microextraction techniques to determine hormones and pharmaceuticals in environmental water samples by liquid chromatography-tandem mass spectrometry. Compounds Matrix Extraction Technique Optimal Times Handling Recovery Accuracy (%) LOD (ng·L−1) Ref. Estrogens (estrone, 17β-estradiol, estriol, ethynil estradiol, diethylstilbestrol) Wastewater, river water IT-SPME 20 draw/eject cycle 30 min Lower handling 48 samples/day 86.1–106.8 2.7–11.7 [85] Sulfonamide antibiotics (sulfaguanidine, sulfacetamide, sulfadiazine, sulfathiazine, sulfapyridine, sulfamerazine, sulfamethazine, sulfamethoxazole, sulfadimethoxine, sulfasalazine) Wastewater SPME Extraction: 20 min Desorption: 30 min Easy to use 29–229 9000–55300 [88] Antibiotics (sulfamethazine, sulfisoxazole, sulfamethoxazole, sulfadimethoxine, sulfapyridine, trimethoprim, roxithromycin, erythromycin, clarithromycin) Wastewater SPME Extraction: 30 min Desorption: 10 min Easy to use – 2.8–410.0 [89] Analgesic and anti-inflammatory, antidepressant, antibiotics, lipid regulator, β-blockers, diuretics, ansiolitics, antiepileptic, antipsychotic Wastewater dSPME Extraction: 30 min Desorption: 10 min Minimizes laborious and complicated sample preparation procedures 89.2–109.7 5.0–50.0 (LOQ) [90] Pharmaceuticals (carbamazepine) Wastewater TFME - 96 well-plate – – [91] Fluoroquinolones (enoxacin, ofloxacin, ciprofloxacin, norfloxacin, lomefloxacin) Surface water and wastewater IT-SPME 20 draw/eject cycles 30 min Lower handling 48 samples/day 81.8–98 7.0–29.0 [92] Non-steroidal anti-inflammatory drugs (acetaminophen, ibuprofen, naproxen, fenoprofn, flurbiprofen, loxoprofen, ketoprofen, mefenamic acid, flufenamic acid, diclofenac, tolfenamic acid, oxaprozin, phenylbutazone, indomethacin, acemetacin) Surface water and wastewater IT-SPME 20 draw/eject cycles 30 min Lower handling 48 samples/day 80.4–100.4 5.0–65.0 [93] Pharmaceuticals (paracetamol, naproxen, diclofenac, caffeine, antipyrine, propanolol, carbamazepine) River water and wastewater SBSE Extraction: 240 min Desorption: 20 min Practical 10–92 10.0–50.0 [94] Pharmaceuticals (paracetamol, caffeine, antipyrine, propranolol, carbamazepine, ibuprofen, diclofenac) River water and wastewater SBSE Extraction: 240 min Desorption: 15 min Practical 9–110 10–50 [95] Molecules 2014, 19 10340 Table 3. Cont. Compounds Matrix Extraction Technique Optimal Times Handling Recovery Accuracy (%) LOD (ng·L−1) Ref. Pharmaceuticals (paracetamol, caffeine, antipyrine, propranolol hydrochloride, pridinol methanesulfonate, carbamazepine, diclofenac) Wastewater SBSE Extraction: 60 min Desorption 10 min Better than commercial coatings 1–50 15–50 [96] Statin drugs (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin) Pure water, wastewater and river water DLLME Centrifugation: 10 min (two times) Faster 13–92 0.09–17.0 [97] SBSE Extraction: 72 min Desorption: - 0–38 0.08 Anti-inflammatory (paracetamol, ketoprofen, naproxen, ibuprofen, flufenamic acid, tolfenamic acid) β-blockers (metoprolol, bisoprolol, betaxolol) Wastewater US-IL-DLLME Vortexed: 1 min Sonicated: 4 min Ice-water: 3 min Centrifugation: 8 min Friendly 88–111 0.2–60.0 [98] Antiinflammatory (diclofenac, ketoprofen, ibuprofen, naproxen) River and tap water DLLME Sonicated: 1 min Centrifugation: 10 min (two times) Simple and rapid 71–85 0.1–3.0 [99] Clotrimazole River water and wastewater DLLME Extraction: 1 min Centrifugation: 10 min 67.9–99.2 0.20–0.21 [100] Acidic drugs (peroxicam, ketorolac, clofibric acid, naproxen, bezafibrate, fenoprofen, ibuprofen, diclofenac, indomethacin) Wastewater HF-LPME Extraction: 45 min Poor precision-manual operation 80–111 0.15–12.6 [101] Antidepressant (amitriptyline, clomipramine, doxepin, mianserine, nortriptyline) Wastewater HF-LPME Extraction: 120 min Relatively simple 33–49 0.005–0.030 [102] Antibiotic residue (erythromycin, spiramycin, tilmicosin, sulfathiazole, sulfamethazine, sulfamerazine, oxytetracycline, tetracycline, ciprofloxacin, danofloxacin, enrofloxacin) River water HF-LPME Extraction: 60 min Simple 79.2–118 10.0–250.0 [103] Molecules 2014, 19 10341 Zgoła-Grześkowiak [99] used DLLME with LC-MS detection to extract anti-inflammatory pharmaceuticals from environmental samples. Chloroform was the extractant, and acetone was the dispersant. Under the optimised conditions, a two-step extraction with sonication was used; the LOQs ranged from 0.5 to 10 ng·L−1. Zgoła-Grześkowiak and Grześkowiak [100] developed a similar microextraction technique using ethanol as the dispersant and trichloroethylene as the extractant for the determination of clotrimazole in river water and wastewater effluent samples from wastewater treatment plants. The LOQ was approximately 0.7 ng·L−1. Hollow fibre-protected liquid-phase microextraction (HF-LPME) was used by different researchers. Quintana et al. [101] used a hollow fibre liquid-phase microextraction (Accurel Q3/2 polypropylene tubular membranes) to extract/enrich acidic drugs from wastewater samples. After optimising the LPME method, very clean extracts could be obtained, avoiding signal suppression during the LC-MS/MS analysis of the analytes; the limits of quantification ranged from 0.5 to 42 ng·L−1. Additionally, Ho et al. [102] developed a similar technique able to accommodate large-sample-volume extractions in a single step for extracting antidepressant drugs from environmental waters. Compared to studies with small sample volumes, the closure of the hollow fibre and the type of liquid membrane were critical for large-volume extractions. Finally, Yudthavorasit et al. [103] used HF-LPME with UHPLC-MS/MS to determine 11 antibiotics in river water samples. The parameters were optimised to provide LODs from 10 to 250 ng·L−1. Good recoveries (79.2%–118%) were obtained using this technique, except in the study conducted by Ho et al. [102]. However, the authors obtained better enrichment factors by using large sample volumes, obtaining LODs in the range of pg·L−1. 5. Conclusions and Future Trends LC–MS techniques are established methods for analysing organic micropollutants in environmental samples. These techniques can be applied to thermally labile compounds, and derivatisation is unnecessary for highly polar compounds. Mass analyser hybrid instruments that can identify metabolites and transformation products from their parent compounds have been introduced. Extraction techniques have also improved, and greener methodologies that consume less solvent have been introduced. Therefore, microextraction techniques can be combined with new extractants. Athough many ILs are not biodegradable and some are used as pesticides, they are safe extractants by low vapor pressure, and the improvements derived from these new materials, including MIPs and/or nanomaterials, and the development of novel devices are the most studied topics in analytical chemistry today. These advances might be economically and environmentally favourable because they decrease the environmental and economic impact of analytical chemistry laboratories, prevent exposure of the laboratory personnel to the vapours of harmful compounds and mitigate the problems caused by long and intensive sample pretreatments, which result in analyte losses and contamination [47]. Acknowledgments The authors would like to acknowledge our colleague, Mariana López Sánchez, who recently left us. Molecules 2014, 19 10342 Author Contributions M.E.T.-P., Z. S.-F. and J.J. S.-R. designed research; M.E.T.-P. and C. A.-O. performed research and analyzed the data; M.E.T.-P., C. A.-O., Z. S.-F. and J.J. S.-R. wrote the paper. All authors read and approved the final manuscript. Conflicts of Interest The authors declare no conflicts of interest. References and Notes 1. Farajzadeh, M.A.; Nouri, N.; Khorram, P. 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