Journal of Chromatography A, 1152 (2007) 14–31

Review

New materials in sorptive extraction techniques for polar compounds

N. Fontanals, R.M. Marcé ∗ , F. Borrull
Departament de Quı́mica Analı́tica i Quı́mica Orgànica, Universitat Rovira i Virgili, Campus Sescelades, Marcel lı́ Domingo, s/n, 43007 Tarragona, Spain
Available online 20 December 2006

Abstract
This paper provides an overview of the new developments in material and format technology that improve the extraction of polar compounds
in several extraction techniques. They mainly include solid-phase extraction, but there are also other sorptive extraction techniques, such as stir
bar sorptive extraction and solid-phase microextraction that use either fibers or in-tube devices. We focus on new synthesised materials that are
both commercially available and “in-house”. Most novel materials that enhance the extraction of polar compounds are hydrophilic and have large
specific surface area; however, we also cover other leading technologies, such as sol–gel or monolith. We describe the morphological and chemical
properties of these new sorbents so that we can better understand them and relate them to their capability of retaining polar compounds. We discuss
the extraction efficiency for polar compounds when these polymers are used as sorptive material and compare them to other materials. We also
mention some representative examples of applications.
© 2006 Elsevier B.V. All rights reserved.

Keywords: Polymeric sorbents; Hydrophilic materials; Novel coatings; Sorptive techniques; Polar compounds

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2. Sorbents for solid-phase extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.1. Hydrophobic polymeric sorbents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.2. Hydrophilic polymeric sorbents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.2.1. Copolymers with a hydrophilic monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.2.2. Chemically modified sorbents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.3. Mixed-mode ion-exchange sorbents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.4. Other materials tested for SPE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3. Coatings for microextraction-related techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.1. New materials for solid-phase microextraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.2. New coatings for in-tube solid-phase microextraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.3. Stir bar sorptive extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
4. New sorptive extraction formats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

1. Introduction achieve detection limits that are as low as legislation requires

but also to clean up the sample matrix. The most popular sample
Sample preparation is often considered to be a fundamental preparation technique for liquid samples is solid-phase extrac-
step in analytical procedures, because it helps not only to tion (SPE), which has already replaced liquid–liquid extraction
(LLE). SPE has been used extensively in the purification and
concentration of several analytes from complex matrices, such
∗ Corresponding author. Tel.: +34 977 55 81 70; fax: +34 977 55 84 46. as environmental and biological samples. Of special interest
E-mail address: rosamaria.marce@urv.cat (R.M. Marcé). are the achievements of SPE in the extraction of polar analytes

0021-9673/$ – see front matter © 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.chroma.2006.11.077
 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31 15

from complex aqueous samples, because it is difficult to most suitable because of their chemical stability and broad range
isolate and preconcentrate them. Solid-phase microextraction of physico-chemical characteristics. The type of sorbent, its
(SPME), which was ideally designed to be coupled to gas structure and its interactions with the solute are clearly related
chromatography (GC), is gaining popularity for extraction of to the efficiency of the extraction process. Thus, when new
polar compounds from liquid samples. This enhancement in materials are being developed, it is equally important to define
SPME for extraction of polar analytes might be thank to the last both their chemical structure, which determines the type of
improvements, in both coating and format technology [1–4]. interactions, and their morphology (i.e. specific surface area, dis-
SPE and SPME are sorptive techniques, so retention is due to tribution of pore diameter, particle size, etc.), which determines
reversible hydrophobic, polar and ionic interactions between the the mechanical properties and, eventually, the stability of the
analyte and the sorptive material. The type of sorbent or coating resin. In this section, we describe polymeric sorbents, together
used in SPE and SPME, respectively, is, therefore, responsible with their chemical and morphological properties, which have
for the efficiency of the extraction process. The availability of been progressively developed in recent years to be used as SPE
different materials is one of the advantages that sorptive tech- packing materials.
niques have over other extraction techniques. The rising number
of publications in this field strongly supports this claim [1,5]. 2.1. Hydrophobic polymeric sorbents
The classical sorbents in SPE are silica-based (C2 , C8 , C18 ),
carbons or polymeric (basically poly(styrene-divinylbenzene), The traditional polymeric sorbent is macroporous PS-DVB
PS-DVB). More recently, hydrophilic polymeric sorbents have (structure in Table 1), which has a hydrophobic structure with
been used which, as a general rule, have a high specific sur- a specific surface area up to 800 m2 g−1 . It interacts with the
face area (that increases the number of points of interaction analytes (due to the hydrophobic character of the sorbent)
with the analyte) and are hydrophilic (thus defining the type of basically through Van der Waals forces and ␲–␲ interactions
interactions suitable for correlation with polar analytes) [6,7]. of the aromatic rings that make up the sorbent structure.
Molecularly imprinted polymers (MIPs) yield specific binding Some examples of commercial polymeric resins (also shown
sites within a polymeric matrix, so that, they enhance selectiv- in Table 1) are: PLRP-S-10 (500 m2 g−1 ) and PLRP-S-30
ity. As well as selectively extracting the target compound, they (350 m2 g−1 ), both from Polymer Lab. (Shropshire, UK)
are also helpful in cleaning up complex matrices [8,9]. Another and Amberlite XAD-2 (300 m2 g−1 ) and Amberlite XAD-4
advantage of SPE is the column-like format, which means that (880 m2 g−1 ) from Rohm & Haas (Philadelphia, PA, USA),
almost all types of sorbents (whatever their morphological or and Strata SBD-L (500 m2 g−1 ) from Phenomenex (Torrance,
chemical structure would be) can be packed in a straightforward CA, USA).
manner [6,10]. In the extraction of polar compounds using these hydrophobic
The initial SPME format, on the other hand, is a station- sorbents, one of the most important parameters to control is the
ary phase coating onto an extraction fiber, which restricts the specific surface area, as the higher the specific surface area, the
morphology and chemistry of the coatings to those that can be larger the number of ␲–␲ sites available to interact with the
deposited onto the fiber. Thus, the applicability of this technique compounds. Thus, one way to improve the extraction efficiency
has always been subjected to a limited number of commercially of these hydrophobic sorbents is to increase the specific surface
available fibers. The coatings that are commercially available area.
are polydimethylsiloxane (PDMS), polyacrylate (PA), carboxen Highly crosslinked sorbents are macroporous PS-DVB poly-
(CAR) and carbowax (CW) and divinylbenzene (DVB) in dif- mers that are prepared with optimised conventional methods but
ferent combinations, which just cover almost same range of with a high loading of crosslinking agent (DVB), which results
polarity. The in-tube format of SPME (in which the phase coats in specific surface areas up to 800 m2 g−1 . As an alternative,
a capillary column) increases the availability of coatings for this hypercrosslinked resins can increase specific surface areas to
technique and also solves other drawbacks of the fiber format, as high as 2000 m2 g−1 . These resins are obtained by a novel
such as the advance in the coupling to liquid chromatography method introduced by Davankov in the early 1970s which con-
(LC) [11,12]. sists of extensive post-crosslinking of linear polystyrene chains
This article reviews the new commercially available or “in- by means of the Friedel-Crafts reaction. This produces vari-
house” materials that have been developed to improve the ous structural bridges between neighbouring phenyl groups in a
classical SPE sorbents and SPME coatings and, in turn, enhance highly swollen state [13–15].
the extraction of polar compounds. As well as the progress in Some of the commercial hypercrosslinked resins are Sty-
material technology, this review also covers new formats in sorp- rosorb 2 m (910 m2 g−1 ), Styrosorb MN-150 (1070 m2 g−1 ) and
tive techniques that attempt to improve the extraction of polar Styrosorb MT-430 (1050 m2 g−1 ), all of which are from Puro-
analytes from complex aqueous matrices. lite Int. (Pontyclun, UK); LiChrolut EN (1200 m2 g−1 ) from
Merck (Darmstadt, Germany); HySphere-SH (>1000 m2 g−1 )
2. Sorbents for solid-phase extraction from Spark Holland (Emmen, The Netherlands); Envi-Chrom P
(800–950 m2 g−1 ) from Supelco (Bellefonte, PA, USA); Baker-
Numerous materials can be used as SPE sorbents. Classically, bond SBD1 (1060 m2 g−1 ) from J.T. Baker (Deventer, The
they are divided into silica-based, carbon-based and macrop- Netherlands), and Amberchrom GC-161m (900 m2 g−1 ) from
orous polymeric sorbents. Of these, polymeric sorbents are the TosoHaas (Stuttgart, Germany) (Table 1).
16 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

Table 1
Structure and properties of some polymeric commercial sorbents
Copolymer structure Sorbent Area (m2 g−1 ) Supplier

Macroporous XAD-1 100 Room & Haas

XAD-2 300 Room & Haas
XAD-4 ≥750 Room & Haas
XAD-16 800 Room & Haas
PLRP-S-10 500 Polymer Lab.
PLRP-S-30 375 Polymer Lab.
Strata SBD-L 500 Phenomenex

PS-DVB Styrosorb 2 m 910 Purolite Int.

Styrosorb MT-43 1050 Purolite Int.
Styrosorb MN-150 1070 Purolite Int.
HySphere-SH >1000 Spark Holland
Amberchrom GC-161 m 900 TosoHaas
Hypercrosslinked Envi-Chrom P 800–950 Supelco
Bakerbond SDB-1 1060 J.T. Baker
LiChrolut EN 1200 Merck
Chromabond HR-P 1200 Macherey-Nagel

Some studies have shown that hypercrosslinked sorbents pro- Introducing a polar monomer into the resin, as Thurman and co-
vided better recoveries than sorbents with a lower crosslinking workers [18] described in their early study, where they compared
degree (and therefore with a lower specific surface area). For the hydrophobic XAD resins (XAD-1, XAD-2 and XAD-4) with
instance, the hypercrosslinked resin Hysphere-SH gave better the hydrophilic resins (XAD-7 and XAD-8) in the extraction of
recoveries than conventional macroporous resin PRLP-S in the fulvic acids from water samples, favours interaction with water,
on-line SPE of substituted phenols [16] and anilines [17]. because the resin pores expand, and thus help the compounds to
penetrate the resin.
2.2. Hydrophilic polymeric sorbents More recently, another MA-DVB resin has been marketed
under the trademark of Abselut Nexus (Varian, Palo Alto, CA,
Despite the high specific surface areas of these resins, their USA) (575 m2 g−1 ). This sorbent has been used to clean up
hydrophobic nature and their interactions with the analytes are complex matrices, such as blood [19], urine [19,20], plasma
only hydrophobic, which leads to poor retention in the extraction [21,22] and animal tissue [23]. An extra advantage of Abselut
of polar compounds. One solution to this problem is to intro- Nexus is that it is not necessary to condition the cartridge before
duce polarity into the resins, thus favouring the polar interaction extraction, which is a development known as non-conditioned
between sorbent and analyte, and enhancing the recoveries for SPE (NC-SPE) [24]. This approach was successfully applied
this type of analytes. In recent years, some of the research in [20] when Abselut Nexus was compared to another hydrophilic
the field of new SPE materials has focused on the development copolymeric sorbent, Oasis HLB (information about this sorbent
of new hydrophilic polymeric materials. In the section below, below), and silica modified C18 in the extraction of methadone
we discuss several approaches to obtain hydrophilic sorbents enantiomers and benzodiazepines from serum and urine. The
and describe how they can be applied in SPE. The hydrophilic performances of these two polymeric sorbents were not signifi-
sorbents can be prepared by copolymerising monomers that con- cantly different, and were better than that of the silica modified
tain suitable functional groups or by chemically modifying the resin. However, Abselut Nexus was selected for this applica-
PS-DVB hydrophobic polymers with a polar moiety. tion because the sorbent did not need the column to be activated
with methanol and water before use. On the other hand, some
2.2.1. Copolymers with a hydrophilic monomer studies [19,21] demonstrated that the efficiency of the extraction
The first commercially available hydrophilic sorbents were with Abselut Nexus decreases when the extraction protocol was
the series of Amberlite XAD from Rohm & Haas, with the without the conditioning step.
introduction of Amberlite XAD-7 and Amberlite XAD-8. Both Varian also commercialises the sorbent Focus which,
sorbents are based on a methacrylate-divinylbenzene (MA- according to the information provided by the supplier, is a polar-
DVB) copolymeric structure with a specific surface area of 310 enhanced sorbent. To the best of our knowledge, no studies have
and 450 m2 g−1 , respectively (the details and some applications been published on Focus as SPE sorbent.
of all the resins described in Table 2). These sorbents combine a Oasis HLB (Waters, Milford, MA, USA) was one of the
polar monomer (MA), which promotes hydrophilic interactions, first hydrophilic sorbents to be commercially available. It is
and a crosslinking monomer (DVB), which helps to increase a macroporous poly(N-vinylpyrrolidone-divinylbenzene) (PVP-
the specific surface area and enhance lipophilic interactions. DVB) copolymer and has a specific surface area of ∼800 m2 g−1
 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31 17

Table 2
Structure, properties and application of some commercial hydrophilic polymeric sorbents
Sorbent Supplier Copolymer structure Surface area (m2 g−1 ) Analyte Matrix Technique Ref.

XAD-7 Room & Haas 450 Fulvic acids Water Batch-SPE–UV–vis [18]
XAD-8 310

Abselut Nexus Varian MA-DVB 575 Isoflavones Plasma Off-line-SPE–LC–MS [22]

Drugs Urine & serum Off-line-SPE–LC–UV–vis [20]
Tetracyclines Animal tissue Off-line-SPE–LC–DAD [23]
Fatty acids Animal tissue Off-line-SPE–GC–FID [21]
Focus n.d. n.d. n.d. n.d. n.d.

Oasis HLB Waters 830 Antibiotics Water On-line-SPE–LC–MS/MS [36]

Pesticides
Herbicides Off-line-SPE–LC–MS/MS [32]
EDCs Off-line-SPE–LC–MS [47]
Biological comp. Urine & plasma Off-line-SPE–LC–UV–vis [27]
Plasma 96-well-SPE–LC–MS/MS [46]
Porapak RDX PVP-DVB 550 Nitroaromatic Water Off-line-SPE–LC–UV–vis [48]
Anilines Off-line-SPE–LC–ED/MS [159]

Discovery DPA 6S Supelco n.d. EDCs Water Off-line-SPE–GC–MS [49]

Polyamide Alkyl amines [50]

xl: Crosslinked with DVB; n: linear polymer; n.d.: no data. Detectors: UV–vis: ultraviolet–visible; MS: mass spectrometry; DAD: diode array; FID: flame ionisation.

(Table 2). Oasis HLB has been widely used in SPE and some shown the same potential and satisfactory results as Oasis HLB,
of the applications can be seen in Table 2. Basically, it has been perhaps because of its lower specific surface area (550 m2 g−1
used to extract and clean up several analyte types from biological in contrast to 830 m2 g−1 ). For instance, on the one hand, Oasis
matrices [25–28] and to extract pollutants, such as phenols [29], HLB provided higher recoveries than LiChrolut EN (PS-DVB,
pesticides [30–32] and pharmaceuticals [33–36] from aqueous 1200 m2 g−1 ) when extracting a group of weak acid endocrine-
samples. disrupting compounds (ECDs) [47]. The authors attributed this
More interesting are the studies which compare the feasibility to the hydrophilic-lipophilic balance of the Oasis HLB mate-
of Oasis HLB to other hydrophobic polymeric sorbents for the rial, which allows a stronger retention of the ionised analytes.
extraction of different groups of compounds [37–43]. Most of On the other hand, LiChrolut EN was preferred over Porapak
the studies mentioned above show the potential of Oasis HLB in RDX when explosive compounds containing nitrobenzene moi-
the extraction of compounds with high polarity. Oasis HLB will ety were extracted. This is also due to highly increased surface
be compared with other similar hydrophilic sorbents throughout area (1200 m2 g−1 ) and ␲–␲ interactions between LiChrolut EN
this section. and the aromatic groups of the compounds [48].
Most of the studies investigate the performance of Oasis HLB Discovery DPA-6S (Supelco) (Table 2) is another hydrophilic
in off-line SPE using the different cartridge sizes available (from sorbent based on polyamide but, unlike the sorbents described
30 to 500 mg). Nevertheless, other studies use it in other formats: above, its specific surface area is only a few square meters per
for example, packed in a SPE precolumn [36] and leading to a gram due to its linear polymeric structure. It was compared
completely automated system, packed in a turbulent flow col- to other polymeric sorbents in the extraction of ECDs [49]
umn [44,45] or using a 96-well plate [46] which simultaneously and alkyl amines [50], but it was not the sorbent of choice
enables several extractions to be performed at the same time and in any of the studies because its recoveries were low, which
the use of microliters as the elution solvent, thus avoiding the might be because of the lack of specific surface area of the
evaporation and reconstitution steps. sorbent.
Porapak RDX is another commercial sorbent from Waters Apart from the several commercial hydrophilic sorbents,
based on the same N-vinylpyrrolidone-divinylbenzene structure. mainly Oasis HLB, there are some research groups that have
In spite of having the same structure, Porapak RDX has not synthesised hydrophilic polymers to be used as SPE sorbents.
18 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

Table 3
Structure, properties and application of some “in-house” hydrophilic polymeric sorbents
Sorbent Copolymer structure Surface area (m2 g−1 ) %wt. polar content Analytea Technique Ref.

AN-DVB 460b 5.9% Nb Phenols Batch-SPE–UV–vis [51]

MAN-DVB R = H; AN-DVB 560b 4.8% Nb

R = CH3 ; MAN-DVB

CMPS-DVB 308b 2.6% Nb [52]

PANI 48 n.d. Phenols Off-line SPE–GC–ECD [53,55]

Polar pesticides Off-line-SPE–CE–DAD [54]

PNMA R = H; PANI 32 n.d. Phenols Off-line-SPE-GC-ECD/FID [55]
PDMA R = CH3 ; PNMA 38 n.d.
R = phenyl; PDMA

PPy 40 n.d. Phenols Off-line-SPE–GC–FID/MS [56]

Pesticides
PAHs
Phenols On-line-SPE–LC–UV–vis [57]

NVlm-DVB 626 6.3% N Phenols and On-line-SPE–LC–UV–vis [61]

Polar pesticides Off-line-SPE–LC–UV–vis

4VP-DVB 710 2.1% N On-line-SPE–LC–UV–vis [59]

4Vlm-DVB 504 8.1% N [62]

HXLGp 908 3.96% O [63,64]

HXLGmix 1889 2.95% O

a All in water sample.
b Characterisation for 50:50 ratio resins; xl: crosslinked with DVB; xl2 : hypercrosslinked. Detectors: ECD: electron capture.
 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31 19

In this regard, Trochimczuk’s group [51,52] synthesised a

series of resins based on polar monomers. In the first study [51],
these resins were based on either acrylonitrile (AN) or methacry-
lonitrile (MAN) crosslinked with DVB (Table 3); and, in a recent
study [52], they were based on cyanomethylstyrene (CMSt) also
crosslinked with DVB (Table 3). In both studies [51,52], the
resins were generated with different degrees of polarity and spe-
cific surface areas and their properties were related to the initial
percentage of each monomer, i.e. polar or crosslinker. Then,
these resins were tested in the sorption of phenols and it was
found that the best sorption properties were for the resins with a
50:50 ratio; thus, the authors concluded that both effects (polar- Fig. 1. Recovery values after 100 mL (), 200 mL (), and 300 mL ( ) (just for
ity and specific surface area) were equally important. Among HXLGp and HXLGmix) of standard solution spiked with phenol, at a constant
three 50:50 ratio resins, the best sorption properties were for the amount injected of 0.2 ␮g, was percolated through a precolumn packed with
“in-house” hydrophilic sorbents (Table 3) in SPE–LC–UV–vis.
AN-DVB resin, since it combines a relatively high specific sur-
face area (460 m2 g−1 ) and the highest nitrogen content (5.9%
N) of the three. Fig. 1 shows, the best results were obtained with NVIm-DVB,
Another example is the conductive resins synthesised by which has both the highest specific area and the quite high nitro-
Bagheri’s group. They are based on polyaniline (PANI) gen content. Therefore, both parameters contribute equally to
[53,54], poly-N-methylaniline (PNMA) [55], polydiphenylani- the enhanced retention of polar compounds.
line (PDPA) [55], and polypyrrole (PPy) [56,57] (Table 3). All In further studies, our research group also prepared hyper-
these resins are hydrophilic and their specific surface areas are crosslinked resins [63], which have different hydroxyl group
not higher than 40 m2 g−1 , because they are linear polymers. contents (depending on the precursor) and specific surface areas
After the synthesis, their SPE performance was tested in the (the characterisation details for each hypercrosslinked resin are
extraction of phenol and a group of chlorophenols. The perfor- also shown in Table 3). These hypercrosslinked resins were also
mance of the synthesised sorbents was subsequently compared evaluated as SPE sorbents for the extraction of polar compounds
with the commercial LiChrolut EN (PS-DVB, 1200 m2 g−1 ) and [64]. For example, Fig. 1 shows that the recovery obtained when
Oasis HLB (PVP-DVB, 800 m2 g−1 ). The results obtained by percolating 300 mL of phenol solution through HXLGp (high
off-line SPE of chlorophenols with the in-house produced sor- hydroxyl content) was 72%, whereas when HXLGmix (low
bents were similar to those found with LiChrolut EN and Oasis hydroxyl content) was used, the recovery decreased to 33%.
HLB; however, the commercial sorbents provided higher recov- Of all sorbents shown in Fig. 1, HXLGp, which combines the
eries for phenol. This might be because of the low specific highest number of hydroxyl groups and a high specific sur-
surface area of the new synthesised sorbents, which leads to face area, provide the highest recoveries. Another remarkable
poor recoveries when a polar compound, such as phenol was feature of this sorbent was that it can on-line preconcentrate
extracted. up to 300 mL of sample with acceptable recoveries. Once
In recent years, our research group has synthesised several again, the retention of polar analytes in SPE was enhanced
SPE sorbents. They were prepared by polymerising a polar when the sorbent had a suitable combination of polar and ␲–␲
monomer and a crosslinking agent (DVB), and the resulting interactions.
polymers combined hydrophilicity and high specific surface
area. These sorbents are based on 4-vinylpyridine-divinyl- 2.2.2. Chemically modified sorbents
benzene (4VP-DVB) [58,59], N-vinylimidazole-divinylbenzene Another approach, which is an alternative to prepare the
(NVIm-DVB) [60,61] and 4-vinylimidazole-divinylbenzene sorbents by copolymerising the suitable monomers, is to pre-
(4VIm-DVB) [62] (Table 3). During the preparation of each pare functionalised polymers by chemical modification. The
series of resins, several parameters of the synthetic procedure first chemically modified sorbents applied to the extraction of
that affected the final balance of polarity and specific surface polar compounds were synthesised by Fritz. The styrenic resins
area were tested. The optimum properties of these resins, in were functionalised with sulfonic [65,66], acetyl and hydrox-
terms of specific surface area and nitrogen content (which are ymethyl [66–68] groups (Table 4 gives the information about
directly related to the polarity of the resin), are shown in Table 3. all these resins). At the end of the 90 s, Masqué et al. modified
All these sorbents were tested as SPE sorbents to extract polar the commercial Amberchrom GC-161 m (PS-DVB, 900 m2 g−1 )
compounds. As an example, Fig. 1 shows the recovery values with acetyl [69], benzoyl [70], o-carboxybenzoyl [71], 2,4-
obtained with these hydrophilic resins and an PS-DVB resin dicarboxybenzoyl and 2-carboxy-3/4-nitrobenzoyl [72]. In all
(728 m2 g−1 ) after 100 and 200 mL of a standard solution spiked instances, the modified resins allowed a more efficient extrac-
with phenol percolated through these sorbents. As we can see tion of the polar compounds than the unmodified analogues. This
in Fig. 1, the recoveries for the PS-DVB sorbent are lower than is because the introduction of polar moieties enhances the polar
those for the other sorbents (which have a hydrophilic part). interactions between the resin and the analytes and also because
These low recoveries indicate that the polar part of the sorbent the presence of the polar groups increase the contact with the
plays an important role in the extraction of polar compounds. As aqueous solution and also with the analytes.
20 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

Table 4
Structure, properties of some “in-house” chemically modified polymeric sorbents
Sorbent structure Analytesa Technique Ref.

Polymer based Chemically modified with (X):

Sulfonic –SO3 H Organic solutes (phenols, Off-line-SPE-GC-FID [65,66]

hydroxy phenols, PAHs, . . .)

Hydroxymethyl –CH2 OH [65,67]

Acetyl [65,67]

Phenols and On-line-SPE–LC–UV–vis [69]

Benzoyl Polar pesticides [70]

o-Carboxybenzoyl [71]

2,4-Dicarboxybenzoyl [72]

2-Carboxy-3/4-nitrobenzoyl [72]

a All in water samples.

Nowadays, there are also several commercially available More recently, Strata-X (PS-DVB-VP, 800 m2 g−1 , Phe-
modified sorbents (Table 5). In most cases, due to a patent pend- nomenex), which has a styrenic skeleton and is modified with
ing, it is not known the functional group that modifies these a pyrrolidone group, was commercialised. Strata-X has been
resins; nevertheless, the functional groups in all the resins must applied in SPE to clean up biological samples, such as plasma
be polar. [77] or milk [78], or to enrich pesticides [62,79] or pharma-
Varian was the first to introduce a chemically modified sor- ceuticals [80] from water samples. Some research studies have
bent under the trademark of Bond Elut PPL (700 m2 g−1 ). This made a comparative evaluation of the efficiency of Strata-X with
sorbent provided better results than the classical carbon-based other SPE sorbents. For instance, Posyniak et al. [81] compared
sorbents [73,74] but not better than the results achieved with Strata-X with other silica-based sorbents modified with C18 and
highly crosslinked hydrophobic sorbents [74] or the chem- C8 , and the polymeric sorbents Bakerbond SBD-1 (PS-DVB,
ically modified resin with o-carboxybenzoyl moieties [73]. 1060 m2 g−1 ) and Oasis HLB (PVP-DVB, 830 m2 g−1 ) for the
Another well-known sorbent is Isolute ENV+ (PS-DVB-OH, extraction of tetracyclines in pig kidney. The recoveries were bet-
1100 m2 g−1 ) (IST, Hengoed, UK), which is a hydroxylated PS- ter with the polymeric sorbents, and they finally chose Strata-X
DVB resin. The recoveries of Isolute ENV+ were similar to or as the extraction sorbent, because it yielded cleaner.
slightly worse than those of Oasis HLB for the extraction of Spe-ed Advanta (Applied Separations, Allentown, PA, USA)
carbamates [75] and polybrominated diphenyl ethers (PBDEs) is another commercially available chemically modified sorbent,
[28] and Oasis HLB and Abselut Nexus for the extraction of with a non-specified functional group. However, after character-
chlorinated pesticides [76]. isation, Sirvent et al. [82] deduced that it is a polymeric sorbent
Table 5
Structure, properties and examples of applications of commercially available chemically modified polymeric sorbents
Sorbent Supplier Sorbent structure Analytes Matrix Technique Ref.

Polymer based Chemically modified with (X) Area (m2 g−1 )

N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

Bond Elut PPL Varian n.d. n.d 700 Phenols Water On-line-SPE–LC–UV–vis [73,74]

Polar pesticides
Isolute ENV+ IST Hydroxyl –OH 1100 Carbamates Water Off-line-SPE–LC–MS [75]
PBDEs Serum Off-line-SPE–GC–MS [28]
Pesticides Serum Off-line-SPE–LC–MS [76]
Quinolones Animal Off-line-SPE–CE–DAD [95]
Tissue

Strata-X Phenomenex Pyrrolidone 800 Quinolones Milk Off-line-SPE–LC–FLD/UV–vis [78]

Pharmaceut. Water Off-line-SPE–GC–MS [80]

Tetracyclines Animal Off-line-SPE–LC–DAD [81]
Pesticides Tissue On-line-SPE–LC–UV–vis [62]
Water Off-line-SPE–LC–UV–vis [79]

Spe-ed Advanta Applied Separations Carboxyla n.d. Phenols Water Off-line-SPE–LC–UV–vis [82,83]

Off-line-SPE–GC–FID [83]
a Characterised in [82]. n.d.: no data. Detectors: FLD: fluorescence.

21
22 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

chemically modified with a carboxyl moiety. The same authors

[82,83] also compared the SPE performance of Spe-ed Advanta
with Isolute ENV+ in the extraction of phenolic compounds from
aqueous samples, and they found that Spe-ed Advanta provided
higher recoveries.

2.3. Mixed-mode ion-exchange sorbents

Other sorbents that are also chemically modified are ion-

exchange sorbents. Of particular interest are the mixed-mode
polymeric sorbents, which combine a polymeric skeleton with
ion-exchange groups, so they can mix two types of interaction
mechanisms: reversed-phase and ionic-exchange.
The first commercially available mixed-mode polymers
were Oasis MCX and Oasis MAX (Waters), which have
Oasis HLB skeleton (polyvinylpyrrolidone-divinylbenzene,
830 m2 g−1 ) chemically modified with sulfonic and quater-
nary amines, respectively. Oasis MCX and Oasis MAX are
classified as strong ion-exchange resins, because of the high
acidic and basic behaviour of the ionic group that modify each Fig. 2. Electropherograms of spiked chicken sample tissues with different sor-
resin, respectively. Recently, the same company commercialised bents. (a) Bond Elut C18; (b) Oasis HLB; (c) SDB-RPS; (d) Oasis MAX.
the weak-ion-exchange sorbents Oasis WCX and Oasis WAX, 50 mM phosphoric acid at pH 8.4; λ = 260 nm; 240 mg kg−1 of each substance.
which have the same Oasis HLB skeleton, but modified with Peak designation: (1) danofloxacin; (2) ciprofloxacin; (3) marbofloxacin; (4)
enrofloxacin; (5) difloxacin; (6) piromidic acid (IS); (7) oxolinic acid; (8) flume-
carboxylic acid and piperazine groups, respectively. Table 6
quine. Reproduced from [95] with permission from Wiley-VCH and the authors.
lists the chemical structures, properties and some applications
of mixed-mode ion-exchange sorbents.
These mixed-mode sorbents are mainly applied to extract samples. However, the recoveries with Oasis HLB decreased in
analytes (charged or not) from complex matrixes, such as the analysis of more complex aqueous samples, such as river
food [84–87], biological fluids [88–94], animal tissue [95,96], water or wastewater, because salts and ionic species, present
wastewater [97] and wood extracts [98,99]. The benefit of the in these complex matrices, interfered during the extraction pro-
ion-exchange capacity is that either the analytes, the interfer- cess. The recoveries for Oasis WAX, on the other hand, were
ences in the sample or even the sorbent chargeability (in the almost constant in all of the samples, since most of the interfer-
case of weak-ion-exchange sorbents) can be switched during ences were effectively removed during the washing step using
the different steps in the SPE; thus, allowing the interference this mixed-mode sorbent.
elimination in the washing step and eluting the analytes more Similarly, Strata-X, which is an PS-DVB resin that is chem-
selectively, just by using a suitable pH combination in each SPE ically modified with a polar group, has been further modified
step. with ionic groups to transform the resin into a mixed-mode
Mixed-mode ion-exchange sorbents are specifically designed ion-exchange resin. In this case, the strong cation-exchange
to interact with ionic species. However, they can also effectively Strata-X-C is modified with a sulfonic group, the weak cation-
retain non-charged species through hydrophobic and hydrophilic exchange resin, Strata-X-CW, is modified with a carboxylic
interactions. For instance, Jiménez-Lozano’s group [95] studied group, and the weak anion-exchange resin, Strata-X-AW, is
the performance of several sorbents, including Isolute ENV+, modified with a diamine group (Table 6 for structural details and
Oasis HLB, Oasis MAX and SBD-RPS (ion-exchange resin examples of applications). Because these resins are new, they are
based on a hydrophobic skeleton) in the extraction of quinolones not in such widespread use as Oasis technology, but Strata-X-
from animal tissue. Oasis MAX showed the best recoveries and C has also been applied in the analysis of plasma [101], food
peak shapes in the subsequent capillary electrophoresis (CE) [102] and urine [103] samples. In the last of these applications, it
analysis. Fig. 2 shows the electropherograms obtained from was compared to Strata-X for extracting the major metabolite of
spiked chicken sample tissue using different sorbents. From this the active principle in marijuana, tetrahydrocannabinol-COOH,
figure, we can see that the peak shape is better when Oasis MAX from urine sample. In this particular case, as the metabolite
was used as sorbent. The improvement in the peak shape might has no cation-exchange sites available, the molecule must inter-
be also attributed to the elution solvent used for Oasis MAX (2% act with Strata-X-C hydrophobically. In the same study, when
formic acid in MeOH) was not the same as for the other three Strata-X and Strata-X-C were compared for extracting groups of
sorbents (1% trifluoroacetic acid in 75:25 acetonitrile:H2 O). paraben and phenolic compounds it was found that mixed-mode
Another example is the comparison of Oasis HLB with Oasis cation-exchange resin Strata-X-C showed better hydrophobic
WAX for the extraction of fluorescent whitening agents from and polar retention characteristics than the neutral polymer
environmental waters [100]. These two sorbents behaved simi- with the same backbone, Strata-X. The authors concluded that
larly when extracting the target analytes from deionised water the superior hydrophobic retention of Strata-X-C is due to the
Table 6
Structure, properties and some examples of applications of mixed-mode polymeric sorbents
Sorbent Supplier Sorbent structure Analytes Matrix Technique Ref.

Polymer based Ionic group Ionic mode

Oasis MCX Waters Oasis HLB (information –SO3 H Strong cation-exchange Drugs Plasma On/off-line-SPE–LC–MS/MS [160]
in Table 2)
Off-line-SPE–LC–MS [88]
Food 96-well-SPE–LC–MS/MS [94]
Herbicides Juice Off-line-SPE–LC–UV–vis [87]
Wood preservation Wood Off-line-SPE–LC–UV–vis [98,99]

Oasis WCX Weak cation-exchange Antibiotics Soil Off-line-SPE–LC–MS/MS [161]

N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

Oasis MAX Strong anion-exchange Antibiotics Water Off-line-SPE–LC–DAD [97]

Drugs Plasma Off-line-SPE–LC–UV–vis [91]

Saliva Off-line-SPE–LC–ED [92]
Penicillin Food Off-line-SPE–LC–UV/MS [84]

Oasis WAX Weak anion-exchange Fluorescent whitening Water Off-line-SPE–LC–MS/MS [100,162]

agent
Pharmaceuticals Off-line-SPE–LC–UV–vis [105]
Strata-X-C Phenomenex Strata-X (information in –SO3 H Strong anion-exchange Drugs Urine Off-line-SPE–GC–MS [103]
Table 5)
Off-line-SPE–LC–UV–vis [103]
Acrylamide Plasma Off-line-SPE–LC–MS [101]
Food Off-line-SPE–LC–MS [102]
Strata-X-C-AW Weak anion-exchange n.d. n.d. n.d.

Strata-X-C-CW Strong cation-exchange n.d. n.d. n.d.

Chromabond EASY Macherel-Nagel n.d. n.d. Weak anion-exchange Pharmaceuticals Water Off-line-SPE–GC–MS [104]
Alkyl amines [50]
Pesticides Serum Off-line-SPE–LC–MS [76]

NVlm-DVB Prepared “in-house” (Information in Table 3) Strong anion-exchange Pharmaceuticals Waters Off-line-SPE–LC–UV–vis [105]

n.d.: no data.

23
24 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

electron withdrawing nature of the sulfonic acid group, which exchange and strong anion-exchange, respectively). From this
induces much more electron polarisation in the neighbourhood comparison, and because of the similarity of NVIm-DVB and
of the aromatic ring which is attached to. In view of the above, Oasis MAX results, the authors concluded that NVIm-DVB
Strata-X-C was selected to extract the marijuana metabolite from behaves like a strong anion-exchange sorbent. Nevertheless,
urine samples, with satisfactory results [103]. by choosing the appropriate SPE protocol, which is crucial if
To the best of our knowledge, no studies have described the analyte recovery and selectivity have to be enhanced, these
the application of Strata-X-AW and Strata-X-CW, presumably mixed-mode ion-exchange resins can be tuned to selectively
because of their novelty. extract charged or non-charged species.
Chromabond EASY (Macherey-Nagel, Düren, Germany)
is another chemically modified sorbent with a weak anion- 2.4. Other materials tested for SPE
exchange group (chemical structure not available), which, apart
from allowing ion-exchange interactions, enhances the polar- Even though bead shaped polymeric sorbents are the most
ity of the resin. Chomabond EASY has been compared [104] usual and the most studied in SPE, other materials have also
to other hydrophobic (LiChrolut EN, Bakerbond SBD-1 and been tested as SPE materials. In this section, we review some
Chromabond HR-P) and hydrophilic resins (Oasis HLB, Abse- of these other materials that have been used as SPE sorbents for
lut Nexus and Isolute ENV+) for the extraction of a group the extraction of polar compounds.
of pharmaceuticals that covers different ranges of acidity and First of all, this review would not be complete without men-
basicity. Unexpectedly, the recoveries for the acidic compounds tioning monolith technology. Monoliths are produced by direct
were lower for Chromabond EASY in compare with the other polymerisation in situ in a mold. They are rigid structures with
hydrophilic resins. The authors explained that these results might a proper balance of pores (small pores to increase the specific
be improved by using a more specific elution protocol for acidic surface area and large to allow the liquid to flow without pres-
compounds (i.e. a basic solution) rather than pure methanol. sure). Monolith technology, also called “stationary phases of
Moving on to home-made sorbents, the NVIm-DVB sorbent the fourth generation”, has caused considerable impact in sep-
(Section 2.2.1 for further details and Table 6 for the chemical aration areas, such as capillary electrochromatography (CEC)
structure), which was initially designed as a hydrophilic sor- and micro- and nano-LC [106,107]. However, monoliths have
bent, has also an ion-exchange feature since, depending on the not yet been applied very much as material for SPE. This might
pH, the imidazole group can be protonated. In a recent study be because monoliths need to have balanced pore structures,
[105], the performance of the NVIm-DVB sorbent was com- which mean that their specific surface areas are lower than those
pared to that of Oasis HLB (reversed-phase), Oasis WAX (weak of packed materials. Only in one early study, the pioneers of
anion-exchange) and Oasis MAX (strong anion-exchange) for the technology (Fréchet and Svec) [108] compared two mono-
the extraction of a group of pharmaceuticals and using the liths, one based on PS-DVB and another on poly(2-hydroxyethyl
suitable SPE protocol in each case (reversed-phase, weak anion- methylacrylate-divinylbenzene) (p(HEMA-DVB)) (Table 7), for

Table 7
Structure, properties and applications of other materials used as SPE sorbents
Sorbent Analytes Matrix Technique Ref.

Material Chemical structure

Monolith p(HEMA-DVB) Phenols Water On-line-SPE–LC–UV–vis [108]

MWCNTs Fullerene ECDs Water Off-line-SPE–LC–FLD [109]

Phthalates Off-line-SPE–LC–DAD [110]
DDT Off-line-SPE–LC–UV–vis [111]
Sulfonamides Tissue On-line-SPE–LC–UV–vis [112]

Silica-based modif. with ␤-cyclodextrins ␤-Cyclodextrin Humic acids Water Batch-SPE–UV–vis [113]
 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31 25

the extraction of phenolic compounds from aqueous samples. 3. Coatings for microextraction-related techniques
The polar monolith provided better results. Apart from SPE,
some other improvements regarding to monolith technology Of all the extraction techniques, SPE is the area in which most
have been developed in other fields. These will be summarised effort has been made to develop new sorbents that enhance the
in Section 3.2 and Section 4. extraction of polar compounds. The research in this area for other
Much more can be expected of monolith technology in sorptive extraction techniques is notably lower, both regarding
the future because, as F. Svec pointed out, monoliths are still to the new commercial materials and research groups developing
teenagers compared to packed columns (mainly in LC, but also new materials. Nevertheless, some research has focused on the
in SPE) [107]. development of new materials for other sorption techniques that
Carbon nanotubes (CNTs) are fullerene structures (Table 7) improve the extraction of polar analytes, which we overview in
(carbon atoms clustering in spherical structures) which consist the sections below.
of graphene cylinders closed at their end with caps containing
pentagonal rings. Multiwalled carbon nanotubes (MWCNTs) 3.1. New materials for solid-phase microextraction
arise when there are many carbon atom layers in the wall of
the nanotubes. The CNTs surfaces have a strong interaction The first commercially available fibers in SPME used poly-
with other molecules and atoms, which results in a promising methylsiloxane (PDMS) and polyacrylate (PA) as coatings.
material in sorption fields, and substitute the active carbon. Cai PDMS is apolar and presents high affinity for the extraction
et al. have used this material as a SPE sorbent for extracting of non-polar compounds. On the other hand, PA is polar and
organic compounds, in particular EDCs [109] and phthalates more suitable for extracting polar compounds. However, both
[110]. Their studies show that MWCNTs are similar to or more phases have linear structure (lack specific surface area), which
effective than silica-based sorbents and PS-DVB sorbents. In in turn means a limited retention when polar compounds are
the last months, two more applications of MWCNTs mate- extracted. More recently, coatings have been blended with
rial as sorbent in SPE appeared in the literature. In one of DVB or carbowax (CW); for example, PDMS-DVB, PDMS-
them, dichlorodiphenyltrichloroethane (DDT) and its metabo- carboxen, CW-DVB and CW-templated resin (CW-TPR) which
lites were efficiently concentrated from real water samples [111]. present larger specific surface areas and have greater potential for
In the other, sulfonamides (SAs) were extracted from egg and extracting polar compounds. Supelco commercialises all these
pork tissue [112]. coatings, with different fiber thicknesses and assemblies. PA and
Liu et al. [113] modified a silica-based sorbent with CW-DVB are the most suitable for the extraction of polar com-
␤-cyclodextrins. ␤-Cyclodextrins (Table 7) combine the pounds, but they are still less efficient than other approaches,
hydrophilicity of their outer part with the hydrophobicity of their such as SPE using hydrophilic sorbents [120].
inner part. This special feature was exploited in the same study In order to improve the retention of polar compounds,
to extract a group of structurally complex compounds, such as some research groups have focused on designing approaches
humic acids. to improve the extraction efficiency for polar compounds. In the
Supramolecular assemblies (hemimicelles/admicelles) are development of new coatings for SPME, it is important to bear
formed by surfactants adsorbed on the surface of metal oxides. in mind that the coating or phase has to be attached to the fiber,
Surfactants and metal oxides form electrostatic interactions and also the chemical and mechanical resistance of the coat-
(hemimicelles) and, after the metal oxide has been saturated, ing (which during the desorption step could be exposed to high
hydrophobic interactions (admicelles). Supramolecular sorbents temperatures or strong organic solvents), aspects that make the
have interesting adsorbing characteristics, because they can development of new coating for SPME more laborious.
be easily tuned by modifying the surfactant and the type of Two recent reviews [11,12] cover all the information, both
assembly formed (hemimicelles or admicelles). In the last few in terms of synthesis and application, about new coatings
years, supramolecular sorbents have been applied to extract for SPME. Briefly, there are two approaches to design polar
organic compounds, such as phenolic compounds [114–116], coatings. One approach is sol–gel technology, which deposits
herbicides [117] or surfactants [115,118] from aqueous organic structures onto inorganic polymeric structures (fiber).
samples. If the organic components are properly selected, the selectivity
Cigarette filter is an inexpensive sorbent that has been of the coating can be tuned to extract more polar compounds.
recently tested [119] to extract polycyclic aromatic hydrocar- Crown-ether [121–126] and calix[4]arenes [127,128] are exam-
bons (PAHs), which are non-polar compounds, from aqueous ples of polar coatings prepared by sol–gel technology. Table 8
samples. In this study, 70 mg of cigarette filter (the compo- summarises the general structure of these new coatings as well
sition of which was not specified) was packed in a column as some of their applications.
on-line connected to LC–UV–vis. In the comparison between Several authors have prepared fibers modified with crown-
C18 and XAD-4 sorbents, in general, cigarette filter provided ether of different chain sizes and chemical composition. After
better results than the conventional sorbent tested. these preparations all studies conclude that the fibers mod-
All the materials mentioned above should be alternatives for ified with crown-ether (whatever its structure was) showed
the extraction of polar analytes. However, much more research better recoveries when determining phenols [124–126], amines
should be done before polymeric materials, well established in [121,123] and organophosphorous compounds [122] than the
SPE field, can be replaced. commercial PDMS, PA, CW-DVB or PDMS-DVB. In gen-
26 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

Table 8
Structure, properties and some applications of in-house prepared SPME coatings
Coating Analytes Matrix Technique Ref.

Name Structure Preparation

Crown-ether Sol–gel technology Organophosphorous Food Fiber-SPME–GC–FPD [122]

Aromatic amines Water Fiber-SPME–GC–FID [123]
Phenols [124,125]
Aliphatic amines Urine [121]

Calix[4]arene Aromatic amines Water Fiber-SPME–GC–FID [127,128]

PAHs [127]
PANI See information in Table 3 Electrodeposition Aliphatic alcohols Water Fiber-SPME–GC–FID [130]
Phenols [133]
Aromatic amines [129]
EDCs Fiber-SPME–LC–FLD [132]
PPY BTEX & alcohols Water Fiber-SPME–GC–FID [134,135]
PAHs In-tube-SPME–LC–UV–vis [135]
Amines
␤-Blockers Water [135]
Urine [136]
Plasma

PPPY BTEX & alcohols Water Fiber-SPME–GC–FID [135]

p(MMA-EGDMA) Monolith Pharmaceuticals Urine In-tube-SPME–LC–UV–vis [139]

Plasma [140]
Fluoroquinones Food In-tube-SPME–LC–UV–vis/FLD [137]
Drugs Animal [142]
Tissue
Biological comp. Urine PPME-CE–DAD [143]

p(AA-VP-Bis) Pharmaceuticals Water In-tube-SPME–LC–UV–vis [163]

Phenols
EDCs
Biological comp.
Amphetamines Urine [141]

Detectors: FPD: flame photometric.

eral, the fibers derived from crown-ether sol–gel have greater the polarity, and the high desorption temperature that solves
potential than the commercial ones because of, basically, three the sample carryover problem. The better performance of
factors: the three-dimensional network in the coating, which the crown-ether fibers was demonstrated in the paper [121]
provides higher specific surface areas and sample capacity; in which three crown-ether-derived fibers and the commer-
the increase in the hydrogen-bond forces and, eventually, cial PDMS and PA were compared for the extraction of
 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31 27

Fig. 3. Comparison of quantities extracted from 1 ␮g mL−1 solutions of tetrafluorobenzoic acid N-hydroxysuccinimide ester amine derivatives: (1) methylamine, (2)
dimethylamine, (3) ethylamine, (4) propylamine, (5) butylamine, (6) pentylamine, (7) hexylamine, with commercial 100 ␮m PDMS and 85 ␮m PA fibers and with
the sol–gel crown-ether fibers: A. 4 -allyldibenzo-18-crown-6; B. 3 -allylbenzo-15-crown-5; C. allyloxyethoxymethyl-18-crown-6, whose structure is depicted in (b)
and specified as 80 ␮m DB18C6, 84 ␮m B15C5, and 82 ␮m 18C6, respectively, in the legend of figure (a). Reproduced from [121] with permission from Vieweg
and the authors.

aliphatic amines (Fig. 3). The three fibers had different sub- lifetime and their stability in strong organic solvents, which
stitutions and different numbers of oxygen atoms in the might be used in SPME–LC. For example, a sol–gel-derived bis-
crown-ether ring. They were 4 -allyldibenzo-18-crown-6, 3 - benzo crown-ether SPME coating can be used over 200 times
allylbenzo-15-crown-5 and allyloxyethoxymethyl-18-crown-6 without damaging the fiber surface while all the commercial
(Fig. 3b). Subsequently, the performance of the same three fibers can only be used about 40–100 times [122].
fibers and the commercial PDMS and PA was compared in More recently, sol–gel technology has been applied to the
the headspace extraction of a group of tetrafluorobenzoic acid derivatization of fibers with calix[4]arene [127,128] (Table 8
N-hydroxysuccinimide ester amine derivatives. From this com- for general structure), which posses well-defined cavities with
parison (Fig. 3a), it was concluded that the fiber derived with polar and non-polar rims (upper and lower rims, respectively).
4 -allyldibenzo-18-crown-6 provided the best results, because Like the crown-ether-derived fibers, the new calix[4]arene fibers
the benzyl rings favour ␲–␲ interactions, and the greater number provided better results than the commercial ones for the extrac-
of oxygen atoms in the crown-ether ring favour polar interac- tion of benzene, toluene, ethylbenzene and xylenes (BTEX),
tions. PAHS (it is worth mentioning that these groups of analytes are
Another feature of the fibers prepared by sol–gel technology non-polar, but to the best of our knowledge they are the only
is that the chemical binding between the surface of the fiber application for these calix[4]arene fibers) [127] and aromatic
and the coating makes them more chemically and thermally sta- amines [127,128], and they were also thermally and chemically
ble than fibers prepared by physical deposition of the coating stable.
on the surface. Thus, most of the crown-ether modified fibers Another way to increase the polarity of the fibers is the
[124–126] are stable over 350 ◦ C, while the maximum temper- electrodeposition of conductive polymers onto the fiber. Again,
atures for commercial fibers are lower (i.e. 280 ◦ C for PDMS or the selection of a polar electrochemical polymer means that
260 ◦ C for PA). The high thermal stability can extend the SPME the properties of the coating can be adjusted to enhance the
range towards compounds with higher boiling points. Another affinity for extracting more polar compounds. For instance,
advantage of the robustness of crown-ether fibers is their longer fibers based on polyaniline (PANI) [129–133], polypyrrole
28 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

(PPY) [131,134,135] and poly-N-phenylpyrrole (PPPY) [135] [135] (structures available in Table 8). Then, they evaluated and
(Table 8) have been used to extract polar analytes from aqueous compared them to some GC capillary columns (SPB-1, PTE-
samples. All these structures were expected to show different 5 SPB-5, Omegawax 250 and Supel-Q-Plot) for the in-tube
extraction efficiencies towards compounds with different func- extraction of heterocyclic amines, groups of polar and non-
tional groups, because they are capable of ␲–␲, polar, hydrogen polar aromatic compounds, organoarsenic compounds [135] and
bonding and even ionic interactions. Ghassempour et al. [131] ␤-blockers [135,136]. In all instances, the PPY and PPPY coat-
investigated the various interactions involved in different forms ings showed better extraction efficiencies than the commercial
of aniline, which included the reduced form (presence of free GC columns, which can be easily explained by the numerous
NH), the ionic form and the oxidized form, in the extraction of types of interactions between these multifunctional (i.e. ␲–␲,
anatoxin-a. They concluded that the reduced form of the polyani- polar, hydrogen bonding and ionic interactions) coatings and the
line is more effective for the extraction of this compound because analytes. Another advantage of electrochemical polymer-coated
it favoured the hydrogen bonding interactions. capillaries over commercial capillaries for in-tube SPME is that
Only one study [132] has compared, the performance of the the extraction efficiency and selectivity can be easily manipu-
newly prepared polyaniline coating with that of the commercial lated by regulating the thickness of the coating (i.e. the number
CW-TRP, which, so far, has been reported to be the most suitable of electrochemical polymer cycles) [135].
fiber for the extraction of the studied analytes (bisphenol A, 4-n- Another way of increasing the thickness of the capillary, and
nonylphenol and 4-tert-octyl phenol) from water samples. The thus, improving the extraction efficiency, is to use capillaries
results showed that polyaniline fibers were more sensitive than with monolithic sorbents, which can be synthesised in situ and
CW-TPR. The same study evaluated the lifetime of the polyani- provide monolithic structures with different kinds of functional
line fibers and showed that the extraction efficiency decreased groups.
after 100 runs. In view of this fact, and taking into account that Feng’s research group prepared monolithic capillaries based
none of the above studies reported about the thermal stability of on poly(methacrylic acid-ethylene glycol dimethacrylate) –
the fibers prepared by electrodeposition, it might be concluded p(MMA-EGDMA) – (Table 8 for structure and applications)
that the fibers prepared by sol–gel technology are more robust. and then applied them to in-tube SPME–LC for the extraction of
Nevertheless, electrodeposition technology performs better in drugs from complex sample matrices, such as human body fluids
other formats, such as in-tube SPME. The following section [137–141], animal tissue [142] or food [137]. The hydrophobic
will cover this variant of the microextraction technique in more polymer bone structure and the acidic pendant groups (from
detail and discuss new developments in coatings. the MAA monomer) make this monolithic polymer suitable
for extracting basic analytes, such as most of the drugs stud-
3.2. New coatings for in-tube solid-phase microextraction ied. Moreover, as some studies have reported [137,138,141],
the biocompatibility of this monolithic structure allow the direct
The main drawbacks of conventional SPME (using fibers) analysis of biological samples with no other manipulation except
are its limited capacity (because the fiber exposes little mate- dilution and/or centrifugation, which simplified the whole deter-
rial, which affects its capacity to extract compounds) and the mination procedure. Fig. 4 shows chromatograms for whole egg
higher complexity of its coupling with LC, which leads to the and egg albumina samples spiked with five fluoroquinolones
automation of SPME–LC. The in-tube configuration of SPME and analysed by p(MMA-EGDMA) monolithic capillary in-
might solve the above mentioned drawbacks, since it is based tube SPME–LC–UV–vis [137], where the matrix peaks at the
on a capillary instead of fibers. Thus, the length and thickness beginning of the chromatogram do not interfere with the separa-
of the column are more easily tunable, and also straightfor- tion of the five fluoroquinolones, even though the detector used
wardly connected to LC. The first applications of in-tube SPME (UV–vis) was non-selective for fluoroquinolones.
involved a short GC capillary column, typically silica modified The same group also synthesised a monolithic capil-
columns being more suitable for the analysis of apolar com- lary based on poly(acrylamide-vinylpyridine-N, N -methylene
pounds. The GC columns (all from Supelco) tested as extraction bisacrylamide), p(AA-VP-Bis) (Table 8), which was expected to
devices for in-tube SPME mainly included silica modified with show greatest ion-exchange interactions with acidic compounds
PDMS, such as SPB-1, PTE-5 and SPB-5, or polyethylene gly- through the pyridyl group. The authors confirmed this hypothesis
col (PEG), such as Omegawax 250 and Supelcowax or porous by using in-tube SPME–LC–UV–vis to extract a group of ana-
DVB, Supel-Q-Plot, or a retention gap made of polar silica tub- lytes, including acidic drugs, phenols and ECDs. The extraction
ing. PEG-modified columns provided better recoveries for the yield for 2,4-dinitrophenol (the most acidic phenolic compound
extraction of polar compounds than the rest of apolar columns; analysed) was 87%, while for phenol (the least acidic and least
however, these recoveries are still not sufficient. Thus, a more hydrophobic compound) it was 6%.
polar coating might improve the efficiency for the extraction of The same authors simplified the in-tube monolithic SPME
polar compounds [11]. device by developing the novel technique called polymer mono-
Similar to SPME fibers, some research groups have attempted lith microextraction (PMME). The extraction device consisted
to synthesise new materials to increase the affinity for the of a regular 1 mL syringe, a poly(MAA-EGDMA) monolithic
extraction of polar compounds. In this regard, Pawliszyn’s capillary (2 cm × 530 ␮m ID) and a plastic pinhead, which con-
group prepared series of electrochemical coatings based on nected the former two components seamlessly [143]. PPME
polypyrrol (PPY) [135,136] and poly-N-phenylpyrrole (PPPY) has been successfully used to extract several angiotensin II
 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31 29

extract a group of PAHs and organophosphorous compounds.

Unfortunately, they did not compare the novel coated stir bar
with the conventional PDMS stir bar.

4. New sorptive extraction formats

In recent years, interest in miniaturised systems, which inte-

grate sample treatment, separation and detection in a single
device, has grown. Here, we briefly describe some strategies
used to integrate SPE into these miniaturised systems.
Monolith technology has been applied in microscale prepara-
tion, developing on-chip SPE [148–150] or ␮-SPE [151], which
can be also directly integrated in the mass spectrometer through a
tip [149–151]. So far, these high-tech devices have been applied
to clean up complex samples [150] or concentrate peptides [151],
rather than concentrate polar compounds.
Another example of ␮-SPE device consists of electropoly-
merisation of PPY on a stainless steel frit that was coupled
on-line to pulsed-eluted (PE)–LC. This ␮-device allowed to
extract 20 ␮l of sample spiked at 10 ␮g l−1 of ochratoxin A.
Recoveries ranged between 65 and 80% depending on the pH
and the complexity of the matrix [152].
Abdel-Rehim and co-workers patented a SPE variation called
microextraction in packed syringe (MEPS), which differs from
Fig. 4. LC chromatograms obtained by in-tube SPME of fluoroquinolones from
SPE in that the sorbent (normally 1 mg) is packed into a syringe
the whole egg and albumin sample at 10 ng mL−1 in spiked whole egg sample (100–250 ␮l) as a plug. Then, this syringe is connected to the
(a) and control whole sample (b); spiked albumin sample (c) and control albumin instrument autosampler, which controls all the SPE steps. Thus,
sample (d). The extraction flow rate was 0.04 mL min−1 ; extraction time was MEPS needs no additional instrumentation for the extraction
10 min. Peak designation: (1) ofloxacin, (2) norfloxacin, (3) ciprofloxacin, (4) procedure. This research group coupled MEPS to LC–MS–MS
enrofloxacin, (5) sarafloxacin. Reproduced from [137] with permission from
Springer Berlin and the authors.
to extract drugs from human plasma [153–157] and to GC–MS to
extract non-polar PAHs from water [158]. The sorbent packed
in MEPS can be the same as for SPE. In one of their studies
receptor antagonists in urine samples [143] and low aliphatic [154], for instance, they compared the performance of three sor-
aldehyde derivatives in human saliva [144]. The authors claimed bents for the extraction of drugs from biological fluids: Isolute
that PMME was easier to prepare and had a greater extraction ENV+, silica modified with C8 and a hydrophilic monolith in
capacity than other microextraction devices [143]. situ prepared. The results showed that Isolute ENV+ performed
better than C8 , followed by the monolithic sorbent.
3.3. Stir bar sorptive extraction The formats described in this section are expected to be better
established in the near future because of the rising interest and
Stir bar sorptive extraction (SBSE) is another sorptive tech- their suitability for miniaturised systems.
nique that also overcomes the limited capacity of SPME fibers.
In SBSE, the coating covers a magnetic stir bar, which means that 5. Conclusions
the phase is 50–250 times greater than in SPME [145]. However,
the main drawback of the SBSE technique is the desorption step, The development of new materials and formats that improve
especially to LC, because of the complexity in the automation. the extraction of polar compounds is a growing research topic in
The only commercially available phase for SBSE is PDMS, sorptive techniques. This is widely demonstrated by the range of
which is commercialised under the trademark of Twister (Gers- commercially available materials as well as numerous research
tel), although recently, the variant dual-phase twisters were also groups working in the field.
commercialised. They consist of a short PDMS tube closed at One of the main focuses is the development of polymer-
both ends with two magnets, and packed with sorbent. So far, based materials that can be easily packed and used as SPE
this dual-phase twister has only been applied using carbon as sorbents, since their chemical and morphological properties can
sorbent, and, for the extraction of polar compounds, it provided be easily modified. Also of considerable significance, however,
better recoveries than that of the conventional PDMS-coated is the research into new strategies for preparing coatings for
SBSE [146]. microextraction-based techniques or novel formats suitable for
It should be mentioned that Liu et al. [147] used sol–gel miniaturised systems.
technology in stir bars to generate a partially hydroxyterminated- Despite all the research in this field during last years, we
PDMS coated stir bar, which was then successfully applied to can still expect further improvements in materials and formats
30 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31

that continue to simplify the sample preparation step of polar [40] E. Ayano, H. Kanazawa, M. Ando, T. Nishimura, Anal. Chim. Acta 507
compounds in complex matrices. (2004) 211.
[41] R. Carabias-Martı́nez, E. Rodrı́guez-Gonzalo, E. Herrero-Hernández, F.J.
Sánchez-San Román, M.G. Prado Flores, J. Chromatogr. A 950 (2002)
References 157.
[42] M.J. López de Alda, D. Barceló, J. Chromatogr. A 938 (2001) 145.
[1] D.E. Raynie, Anal. Chem. 78 (2006) 3997. [43] R. Carabias-Martı́nez, E. Rodrı́guez-Gonzalo, E. Herrero-Hernández, J.
[2] C.J. Koester, A. Moulik, Anal. Chem. 77 (2005) 3737. Hernández-Méndez, Anal. Chim. Acta 517 (2004) 71.
[3] R.K. Gilpin, L.A. Pachla, Anal. Chem. 77 (2005) 3755. [44] A. Asperger, J. Efer, T. Koal, W. Engewald, J. Chromatogr. A 960 (2002)
[4] S.D. Richardson, Anal. Chem. 78 (2006) 4021. 109.
[5] J.S. Fritz, M. Macka, J. Chromatogr. A 902 (2000) 137. [45] A. Asperger, J. Efer, T. Koal, W. Engewald, J. Chromatogr. A 937 (2001)
[6] N. Fontanals, R.M. Marcé, F. Borrull, Trends Anal. Chem. 24 (2005) 394. 65.
[7] N. Masqué, R.M. Marcé, F. Borrull, Trends Anal. Chem. 17 (1998) 384. [46] A.Y. Yang, L. Sun, D.G. Musson, J.J. Zhao, J. Pharm. A 1056 (2004) 131.
[8] E. Turiel, A. Martin-Esteban, Anal. Bioanal. Chem. 378 (2004) 1876. [47] R. Carabias-Martı́nez, E. Rodrı́guez-Gonzalo, P. Revilla-Ruiz, J. Chro-
[9] E. Caro, R.M. Marcé, F. Borrull, P.A.G. Cormack, D.C. Sherrington, matogr. A 1056 (2004) 131.
Trends Anal. Chem. 25 (2006) 143. [48] M. Smith, G.E. Collins, J. Wang, J. Chromatogr. A 991 (2003) 159.
[10] C.W. Huck, G.K. Bonn, J. Chromatogr. A 885 (2000) 51. [49] R. Liu, J.L. Zhou, A. Wilding, J. Chromatogr. A 1022 (2004) 179.
[11] J.B. Quintana, I. Rodrı́guez, Anal. Bioanal. Chem. 384 (2006) 1447. [50] P. Kusch, G. Knupp, M. Hergarten, M. Kozupa, M. Majchrzak, J. Chro-
[12] C. Dietz, J. Sanz, C. Cámara, J. Chromatogr. A 1103 (2006) 183. matogr. A 1113 (2006) 198.
[13] V.A. Davankov, M.P. Tsyurupa, React. Polym. 13 (1990) 27. [51] A.W. Trochimczuk, M. Streat, B. Korlarz, React. Funct. Polym. 46 (2001)
[14] V.A. Davankov, M.P. Tsyurupa, M.M. Ilyin, L. Pavlova, J. Chromatogr. 259.
A 965 (2002) 65. [52] D. Drechny, A.W. Trochimczuk, React. Funct. Polym. 66 (2006) 323.
[15] J.-H. Ahn, J.-E. Jang, C.-G. Oh, S.-K. Ihm, J. Cortés, D.C. Sherrington, [53] H. Bagheri, M. Saraji, J. Chromatogr. A 910 (2001) 87.
Macromolecules 39 (2006) 627. [54] H. Bagheri, M. Saraji, D. Barceló, Chromatographia 59 (2004) 283.
[16] R. Wissiack, E. Rosenberg, M. Grasserbauer, J. Chromatogr. A 896 (2000) [55] H. Bagheri, M. Saraji, J. Chromatogr. A 986 (2003) 111.
159. [56] H. Bagheri, A. Mohammadi, J. Chromatogr. A 1015 (2003) 23.
[17] J. Patsias, E. Papadopoulou-Morkidou, J. Chromatogr. A 904 (2000) 171. [57] H. Bagheri, A. Mohammadi, A. Salemi, Anal. Chim. Acta 513 (2004)
[18] G.R. Aiken, E.M. Thurman, R.L. Malcom, H.F. Walton, Anal. Chem. 51 445.
(1979) 1799. [58] N. Fontanals, R.M. Marcé, M. Galià, F. Borrull, J. Polym. Sci. Part A:
[19] K.A. Georga, V.F. Samanidou, I.N. Papadoyannis, J. Chromatogr. B 759 Polym. Chem. 41 (2003) 1927.
(2001) 209. [59] N. Fontanals, P. Puig, M. Galià, R.M. Marcé, F. Borrull, J. Chromatogr.
[20] H. He, C. Sun, X.-R. Wang, C. Pham-Huy, N. Chikhi-Chorfi, H. Galons, A 1035 (2004) 281.
M. Thevenin, J.-R. Claude, J.-M. Warnet, J. Chromatogr. B 814 (2005) [60] N. Fontanals, R.M. Marcé, M. Galià, F. Borrull, J. Polym. Sci. Part A:
385. Polym. Chem. 42 (2004) 2019.
[21] J. Giacometti, A. Milosevic, C. Milin, J. Chromatogr. A 976 (2002) 47. [61] N. Fontanals, M. Galià, R.M. Marcé, F. Borrull, J. Chromatogr. A 1030
[22] Z. Ma, Q. Wu, D.Y.W. Lee, M. Tracy, S.E. Lukas, J. Chromatogr. B 823 (2004) 63.
(2005) 108. [62] N. Fontanals, M. Galià, R.M. Marcé, F. Borrull, Chromatographia 60
[23] V.F. Samanidou, K.I. Nikolaidou, I.N. Papadoyannis, J. Sep. Sci. 28 (2004) 511.
(2005) 2247. [63] N. Fontanals, J. Cortés, M. Galià, P.A.G. Cormack, R.M. Marcé, F. Bor-
[24] www.varianinc.com, 2006. rull, D.C. Sherrington, J. Polym. Sci. Part A: Polym. Chem. 43 (2005)
[25] A. Ziaková, E. Brandsteterová, J. Liquid Chromatogr. Relat. Technol. 25 1718.
(2002) 3017. [64] N. Fontanals, M. Galià, P.A.G. Cormack, R.M. Marcé, D.C. Sherrington,
[26] D.C. Delinsky, K. Srinivasan, H.M. Solomon, M.G. Bartlett, J. Liquid F. Borrull, J. Chromatogr. A 1075 (2005) 51.
Chromatogr. Relat. Technol. 25 (2002) 113. [65] J.S. Fritz, P.J. Dumont, L. Schimidt, J. Chromatogr. A 691 (1995)
[27] M. Rizzo, D. Ventrice, F. Monforte, S. Procopio, G. De Sarro, M. Anzini, 133.
A. Cappelli, F. Makovec, J. Pharm. Biomed. Anal. 35 (2004) 321. [66] P.J. Dumont, J.S. Fritz, J. Chromatogr. A 691 (1995) 123.
[28] A. Covaci, S. Voorspoels, J. Chromatogr. B 827 (2005) 216. [67] J.J. Sun, J.S. Fritz, J. Chromatogr. 590 (1992) 197.
[29] D.A. Azebedo, S. Lacorte, P. Viana, D. Barceló, Chromatographia 53 [68] J.J. Sun, J.S. Fritz, J. Chromatogr. 522 (1990) 95.
(2001) 113. [69] N. Masqué, M. Galià, R.M. Marcé, F. Borrull, J. Chromatogr. A 771
[30] D.A. Azebedo, S. Lacorte, T. Vinhas, P. Viana, D. Barceló, J. Chromatogr. (1997) 55.
A 879 (2000) 13. [70] N. Masqué, M. Galià, R.M. Marcé, F. Borrull, Analyst 122 (1997) 425.
[31] R. Bossi, K.V. Vejrup, B.B. Mogensen, W.A.H. Asman, J. Chromatogr. [71] N. Masqué, M. Galià, R.M. Marcé, F. Borrull, J. Chromatogr. A 803
A 957 (2002) 27. (1998) 147.
[32] L. Gomides, C.W. Götz, M. Ruff, H.P. Singer, S.R. Müller, J. Chromatogr. [72] N. Masqué, M. Galià, R.M. Marcé, F. Borrull, Chromatographia 50 (1999)
A 1028 (2004) 277. 21.
[33] S. Öllers, H.P. Singer, P. Fässler, S.R. Müller, J. Chromatogr. A 911 (2001) [73] N. Masqué, E. Pocurull, R.M. Marcé, F. Borrull, Chromatographia 47
225. (1998) 176.
[34] D.W. Kolpin, E.T. Furlong, M.T. Meyer, E.M. Thurman, S.D. Zaugg, L.B. [74] N. Masqué, R.M. Marcé, F. Borrull, J. Chromatogr. A 793 (1998) 257.
Barber, H.T. Buxton, Environ. Sci. Technol. 36 (2002) 1202. [75] J.M.F. Nogueira, T. Sandra, P. Sandra, J. Chromatogr. A 996 (2003) 133.
[35] S. Abuin, R. Codony, R. Compañó, M. Granados, M.D. Prat, J. Chro- [76] C.D. Sandau, A. Sjodin, M.D. Davis, J.R. Barr, V.L. Maggio, A.L. Water-
matogr. A 1114 (2006) 73. mann, K.E. Pretson, J.L. Preau, D.B. Barr, L.L. Neddham, D.G. Patterson,
[36] K. Stoob, H.P. Singer, C.W. Goetz, M. Ruff, S.R. Mueller, J. Chromatogr. Anal. Chem. 75 (2003) 71.
A 1097 (2005) 138. [77] D.G. Watson, F.G. Araya, P.J. Galloway, T.J. Beattie, J. Pharm. Biomed.
[37] N.C. Dias, C.F. Poole, Chromatographia 56 (2002) 269. Anal. 35 (2004) 87.
[38] T.N. Decaestecker, E.M. Coopman, C.H. Van Peteghem, J.F. Van [78] M.D. Marazuela, M.C. Moreno-Bondi, J. Chromatogr. A 1034 (2004) 25.
Bocxlaer, J. Chromatogr. A 789 (2003) 19. [79] P. Fidente, C. Di Giovanni, S. Seccia, P. Morrica, Biomed. Chromatogr.
[39] M. Farré, I. Ferrer, A. Ginebreda, M. Figueras, L. Olivella, L. Tirapu, M. 19 (2005) 766.
Vilanova, D. Barceló, J. Chromatogr. A 938 (2001) 187. [80] T. Kosjek, E. Heath, A. Krbavcic, Environ. Int. 31 (2005) 679.
 N. Fontanals et al. / J. Chromatogr. A 1152 (2007) 14–31 31

[81] A. Posyniak, K. Mitrowska, J. Zmudzki, J. Niedzielska, J. Chromatogr. [123] Z. Zeng, W. Qiu, M. Yang, X. Wei, Z. Huang, F. Li, J. Chromatogr. A 934
A 1088 (2005) 169. (2001) 51.
[82] G. Sirvent, M. Hidalgo, V. Salvadó, J. Sep. Sci. 27 (2004) 1524. [124] Z. Zeng, W. Qiu, Z. Huang, Anal. Chem. 73 (2001) 2429.
[83] G. Sirvent, M. Hidalgo, V. Salvadó, J. Sep. Sci. 27 (2004) 613. [125] D. Wang, J. Xing, J. Peng, C. Wu, J. Chromatogr. A 1005 (2003) 1.
[84] K.F. Nielsen, P.W. Dalsgaard, J. Smedsgaard, T.O. Larsen, J. Agric. Food [126] L. Yun, Anal. Chim. Acta 486 (2003) 63.
Chem. 53 (2005) 2908. [127] X. Li, Z. Zeng, S. Gao, H. Li, J. Chromatogr. A 1023 (2004) 15.
[85] A. Becalski, B.P.-Y. Lau, D. Lewis, S.W. Seaman, J. Agric. Food Chem. [128] W. Wang, S. Gong, Q. Cao, Y. Chen, X. Li, Z. Zeng, Chromatographia
51 (2003) 802. 61 (2005) 75.
[86] L. Ge, J.W.Y. Yong, N.K. Goh, L.S. Chia, S.N. Tan, E.S. Ong, J. Chro- [129] H. Minjia, T. Chao, Z. Qunfang, J. Guibin, J. Chromatogr. A 1048 (2004)
matogr. B 829 (2005) 26. 257.
[87] N. Rosales-Conrado, M.E. León-González, L.V. Pérez-Arribas, L.M. [130] D. Djozan, S. Bahar, Chromatographia 59 (2004) 95.
Polo-Dı́ez, J. Chromatogr. A 1076 (2005) 202. [131] A. Ghassempour, N.M. Najafi, A. Mehdinia, S.S.H. Davarani, M. Fallahi,
[88] A. Salvador, D. Dubreuil, J. Denouel, L. Millerioux, J. Chromatogr. B M. Nakhshab, J. Chromatogr. A 1078 (2005) 120.
820 (2005) 237. [132] M. Huang, G. Jiang, Y. Cai, J. Sep. Sci. 28 (2005) 2218.
[89] D. Whittington, E.D. Kharasch, J. Chromatogr. B 796 (2003) 95. [133] H. Bagheri, A. Mir, E. Babanezhad, Anal. Chim. Acta 532 (2005) 89.
[90] J. Yawney, S. Treacy, K.W. Hindmarsh, F.J. Burczynski, J. Anal. Toxicol. [134] J. Wu, J. Pawliszyn, Anal. Chim. Acta 520 (2004) 257.
26 (2002) 325. [135] J. Wu, J. Pawliszyn, J. Chromatogr. A 909 (2001) 37.
[91] C.P.W.G.M.V.-V. Wissen, R.E. Aarnoutse, D.M. Burger, J. Chromatogr. [136] J. Wu, H.L. Lord, J. Pawliszyn, H. Kataoka, J. Microcolumn Sep. 124
B 816 (2005) 121. (2000) 255.
[92] K. Inoue, T. Namiki, Y. Iwasaki, Y. Yoshimura, H. Nakazawa, J. Chro- [137] J.-F. Huang, B. Lin, Q.-W. Yu, Y.-Q. Feng, Anal. Bioanal. Chem. 384
matogr. B 785 (2003) 57. (2006) 1228.
[93] K. Ishii, T. Furuta, Y. Kasuya, J. Chromatogr. B 759 (2001) 161. [138] Y. Fan, Y.-Q. Feng, S.-L. Da, Z.-G. Shi, Anal. Chim. Acta 523 (2004)
[94] M.J. Rose, C. Fernandez-Metzler, B.A. Johns, G.R. Sitko, J.J. Cook, J. 251.
Yergey, J. Pharm. Biomed. Anal. 38 (2005) 695. [139] Y. Fan, Y.-Q. Feng, S.-L. Da, X.-P. Gao, Analyst 129 (2004) 1065.
[95] E. Jiménez-Lozano, D. Roy, D. Barrón, J. Barbosa, Electrophoresis 25 [140] Y. Wen, Y. Fan, M. Zhang, Y.-Q. Feng, Anal. Bioanal. Chem. 382 (2005)
(2004) 65. 204.
[96] D. Richard, B. Ling, N. Authier, T.W. Faict, A. Eschalier, F. Coudore, [141] Y. Fan, Y.-Q. Feng, J.-T. Zhang, S.-L. Da, M. Zhang, J. Chromatogr. A
Anal. Chem. 77 (2005) 1354. 1074 (2005) 9.
[97] E. Benito-Peña, A.I. Partal-Rodera, M.E. León-González, M.C. Moreno- [142] J. Nie, Q. Zhao, J. Huang, B. Xiang, Y.-Q. Feng, J. Sep. Sci. 29 (2006)
Bondi, Anal. Chim. Acta 556 (2006) 415. 650.
[98] T. Miyauchi, M. Mori, K. Ito, J. Chromatogr. A 1095 (2005) 74. [143] M. Zhang, F. Wei, Y.-F. Zhang, J. Nie, Y.-Q. Feng, J. Chromatogr. A 1102
[99] T. Miyauchi, M. Mori, K. Ito, J. Chromatogr. A 1063 (2005) 137. (2006) 294.
[100] H.-C. Chen, S.-P. Wang, W.-H. Ding, J. Chromatogr. A 1102 (2006) 135. [144] H.-J. Zhang, J.-F. Huang, H. Wang, Y.-Q. Feng, Anal. Chim. Acta 565
[101] D.N. Mallet, S. Dayal, G.J. Dear, A.J. Pateman, J. Pharm. Biomed. Anal. (2006) 129.
41 (2006) 510. [145] M. Kawaguchi, R. Ito, K. Saito, H. Nakazawa, J. Pharm. Biomed. Anal.
[102] E. Bermudo, E. Moyano, L. Puignou, M.T. Galceran, Anal. Chim. Acta 40 (2006) 500.
559 (2006) 207. [146] C. Bicchi, C. Cordero, E. Liberto, P. Rubiolo, B. Sgorbini, F. David, P.
[103] S. Huq, A. Dixon, K. Kelly, K.M.R. Kallury, J. Chromatogr. A 1073 Sandra, J. Chromatogr. A 1094 (2005) 9.
(2005) 355. [147] W. Liu, H. Wang, Y. Guan, J. Chromatogr. A 1045 (2004) 15.
[104] S. Weigel, R. Kallenborn, H. Hühnerfuss, J. Chromatogr. A 1023 (2004) [148] C. Yu, M. Davey, F. Svec, J.M.J. Fréchet, Anal. Chem. 73 (2001) 5088.
183. [149] Y. Yang, C. Li, J. Kameoka, K.H. Lee, H.G. Craighead, Lab Chip 5 (2005)
[105] N. Fontanals, B.C. Trammell, M. Galià, R.M. Marcé, P.C. Iraneta, F. 869.
Borrull, U.D. Neue, J. Sep. Sci. 29 (2006) 1622. [150] Y. Yang, C. Li, K.H. Lee, H.G. Craighead, Electrophoresis 26 (2005)
[106] H. Zou, X. Huang, M. Ye, Q. Luo, J. Chromatogr. A 954 (2002) 5. 3622.
[107] F. Svec, C.G. Huber, Anal. Chem. 78 (2006) 2101. [151] D.S. Peterson, T. Rohr, F. Svec, J.M.J. Fréchet, Anal. Chem. 75 (2003)
[108] S. Xie, F. Svec, J.M. Fréchet, Chem. Mater. 10 (1998) 4072. 5328.
[109] Y.Q. Cai, G.B. Jiang, J.F. Liu, Q.X. Zhou, Anal. Chem. 75 (2003) 2517. [152] J.C.C. Yu, E.P.C. Lai, Anal. Bioanal. Chem. 381 (2005) 948.
[110] Y.Q. Cai, G.B. Jiang, J.F. Liu, Q.X. Zhou, Anal. Chim. Acta 494 (2003) [153] Z. Altun, M. Abdel-Rehim, L.G. Blomberg, J. Chromatogr. B 813 (2004)
149. 129.
[111] Q. Zhou, J. Xiao, W. Wang, J. Chromatogr. A 1125 (2006) 152. [154] Z. Altun, L.G. Blomberg, E. Jagerdeo, M. Abdel-Rehim, J. Liquid Chro-
[112] G.-Z. Fang, J.-X. He, S. Wang, J. Chromatogr. A 1127 (2006) 12. matogr. Relat. Technol. 29 (2006) 829.
[113] C. Liu, N. Naismith, J. Economy, J. Chromatogr. A 1036 (2004) 113. [155] M. Abdel-Rehim, P. Skansen, M. Vita, Z. Hassan, L. Blomberg, M. Has-
[114] A. Moral, M.D. Sicilia, S. Rubio, D. Pérez-Bendito, J. Chromatogr. A san, Anal. Chim. Acta 539 (2005) 35.
1100 (2005) 8. [156] M. Vita, P. Skansen, M. Hassan, M. Abdel-Rehim, J. Chromatogr. B 817
[115] M. Cantero, S. Rubio, D. Pérez-Bendito, J. Chromatogr. A 1067 (2005) (2005) 303.
161. [157] M. Abdel-Rehim, J. Chromatogr. B 801 (2004) 317.
[116] T. Saitoh, Y. Nakayama, M. Hiraide, J. Chromatogr. A 972 (2002) [158] A. El-Beqqali, A. Kussak, M. Abdel-Rehim, J. Chromatogr. A 1114
205. (2006) 234.
[117] F. Merino, S. Rubio, D. Pérez-Bendito, Anal. Chem. 76 (2004) 3878. [159] S. Lacorte, M.-C. Perrot, D. Fraise, D. Barceló, J. Chromatogr. A 833
[118] F. Merino, S. Rubio, D. Pérez-Bendito, Anal. Chem. 75 (2003) 6799. (1999) 181.
[119] H.-D. Liang, D.-M. Han, X.-P. Yan, J. Chromatogr. A 1103 (2006) 9. [160] R. Kahlich, C.H. Gleiter, S. Laufer, B. Kammerer, Rapid Commun. Mass
[120] A. Peñalver, E. Pocurull, F. Borrull, R.M. Marcé, Trends Anal. Chem. 18 Spectrom. 20 (2006) 275.
(1999) 557. [161] K.M. Peru, S.L. Kuchta, J.V. Headley, A.J. Cessna, J. Chromatogr. A 1107
[121] L. Cai, Y. Zhao, S. Gong, L. Dong, C. Wu, Chromatographia 58 (2003) (2006) 152.
615. [162] H.-C. Chen, W.-H. Ding, J. Chromatogr. A 1108 (2006) 202.
[122] J. Yu, C. Wu, J. Xing, J. Chromatogr. A 1036 (2004) 101. [163] Y. Fan, M. Zhang, Y.-Q. Feng, J. Chromatogr. A 1099 (2005) 84.