Microchemical Journal 178 (2022) 107423

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Microchemical Journal
journal homepage: www.elsevier.com/locate/microc

Ethylphenidate determination in oral fluids by molecularly imprinted

polymer extraction and ion mobility spectrometry
P. García-Atienza , F.A. Esteve-Turrillas , S. Armenta *, J.M. Herrero-Martínez
Department of Analytical Chemistry, University of Valencia, 50th Dr. Moliner St., 46100 Burjassot, Spain

A R T I C L E I N F O A B S T R A C T

Keywords: Drug abuse can be easily determined by oral fluid analysis, which allows the identification of the parent com­
New psychoactive substances pounds instead of their respective metabolites, thus reducing potential misidentifications in other biological
Oral fluids matrices. A molecularly imprinted polymer (MIP) has been synthetized by bulk polymerization to be employed in
Selective extraction
the selective extraction of ethylphenidate, a new psychoactive substance, in oral fluids. Ethylphenidate was
Solid-phase extraction
Molecularly imprinted polymer
employed as template molecule for the synthesis of MIP, and a non-imprinted polymer (NIP) was also synthe­
sized. Scanning electron microscopy, nitrogen adsorption measurements and infrared spectroscopy were per­
formed to characterize the resulting materials. A simple procedure was proposed based on the use of MIP as solid-
phase extraction (SPE) sorbent for the target analytes in oral samples, followed by its determination by ion
mobility spectrometry, providing a selective and sensitive methodology useful for a fast drug abuse identifica­
tion. Selectivity of the MIP was evaluated by the extraction yield obtained for phenidate analogues and other
conventional drugs, showing a reduced affinity for MIP material. The proposed ion mobility spectrometry (IMS)
procedure has been validated in terms of selectivity, sensitivity, trueness, and precision, giving a limit of
detection of 20 µg L− 1 and quantitative recoveries from 82 to 91% in ethylphenidate spiked oral fluid samples.

1. Introduction dopamine transporter than the noradrenaline transporter, as compared

In the last decade, the world is suffering a challenging and tremen­
dously rapid evolving drug problem known as New Psychoactive Sub­
stances (NPS). NPS, which are defined by the United Nations Office on
Drugs and Crime (UNODC) as “substances of abuse, either in a pure form
or a preparation, that are not controlled by the 1961 Single Convention
on Narcotic Drugs or the 1971 Convention on Psychotropic Substances,
but which may pose a public health threat” [1], are proliferating at an
unprecedented rate. In such definition, the word “new” does not mean
new inventions, but substances that have recently appeared on the
market for recreational uses and that are not included in the afore­
mentioned Conventions. However, definition of NPS does not imply that
all of them are legal substances. By 2018, approximately 273 NPS has
been scheduled under the international drug control conventions [2,3],
including, butyrfentanyl, ethylone, pentedrone, ethylphenidate, and
MDMB-CHMICA, among others.
Ethylphenidate (ethyl phenyl(piperidin-2-yl)acetate) is a NPS psy­
chostimulant drug analogue of methylphenidate that has significantly
greater dopaminergic selectivity, with a 16-fold greater affinity for the
with methylphenidate [4]. Although, ethylphenidate was identified
more than 50 years ago [5], was in the past decade when attained a
relative importance in Europe under the name of “diet coke” or
“nopaine” [6,7]. Ethylphenidate abuse and trafficking was reported to
the European Monitoring Centre for Drug and Drug Addiction
(EMCDDA) Early Warning System in 2011 [8]. However, there is very
limited published material available for this NPS. Data obtained from
internet forums revealed a median age of 23 for ethylphenidate con­
sumers with a range from 19 to 42 years old [9]. Evaluating the specific
effects and harm potential of ethylphenidate is difficult since scientific
literature about the pharmacology, and toxicology of this substance is
limited. Ethylphenidate underwent hydroxylation forming predomi­
nantly ritalinic acid and methylphenidate [10]. The average dose
appeared to be between 10 and 100 mg [9], although higher average
doses of 147.5 mg were also reported [11]. Moreover, total doses of 500
mg ethylphenidate [6], and a daily use up to 1000 mg over a period of
months [12] were also reported. Although no data of oral fluid-to-
plasma ratio for ethylphenidate are available in the scientific litera­
ture, oral fluid-to-plasma ratio for methylphenidate is from 3.2 to 13.1,

* Corresponding author.
E-mail address: Sergio.armenta@uv.es (S. Armenta).

https://doi.org/10.1016/j.microc.2022.107423
Received 9 February 2022; Received in revised form 14 March 2022; Accepted 21 March 2022
Available online 26 March 2022
0026-265X/© 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
P. García-Atienza et al.
which demonstrated an accumulation of the drug in oral fluid [13].
Regarding the concentration of ethylphenidate in biological fluids, it
has been previously reported concentrations of ethylphenidate of 240 µg
L− 1 in paired serum and 980 µg L− 1 in urine [6], 110 µg L− 1 in post-
mortem femoral blood and 23 µg L− 1 in other patient blood sample
[14]. However, authors of those studies concluded that these concen­
trations were not in the directly lethal range compared to the toxic levels
for methylphenidate that start from approximately 500 µg L− 1 in serum.
Determination of ethylphenidate and methylphenidate in biological
samples generally implies the use of liquid chromatography coupled to
tandem mass spectrometry (LC-MS-MS) after an appropriate sample
treatment such as liquid–liquid [15–17] or solid-phase [18,19] extrac­
tions. However, the selectivity offered by those sample treatments is
rather limited, being the analyst forced to use sophisticated instru­
mentation for ethylphenidate determination in biological samples.
Molecularly imprinted polymers (MIPs) are synthetic materials
complementary in shape and functional groups to a template molecule,
which are able to selectively recognize a compound or a family of
compounds with molecular structure similarities. For MIP synthesis,
template molecule is mixed with a monomer in the presence of a
porogenic solvent to create a complex template-monomer. After that, a
cross-linker and an initiator are added to the mixture to initiate the co-
polymerization of monomer and cross-linker, thus obtaining a polymer
with specific cavities for the analyte [20]. MIPs are very stable and
relatively cheap; consequently, this approach has been tackled for
developing selective sample pre-treatment methods. Indeed, MIPs have
been widely applied for psychoactive substances analysis in biofluids
[21]; and these materials have proven to be useful also for the extraction
of compounds from tissue extracts [22]. Different drugs have been iso­
lated from urine using MIPs, such as cocaine [23], amphetamine [24],
Δ9-tetrahydrocannabinol and its main metabolites [25], and several NPS
[26], among others. Other biological matrices have been also used for
the analysis of psychoactive substances, such as hair [27], plasma [28],
and oral fluids [29–31].
The aim of this paper is the synthesis, characterization, and evalu­
ation of a MIP material using ethylphenidate as template molecule,
which can be used as sorbent in the solid-phase extraction (SPE) of the
target analyte and related molecules from oral fluid samples. As far as
we know, this is the first precedent of a synthetized MIP material for the
extraction and preconcentration of ethylphenidate from oral fluids. The
selectivity of the MIP extraction, combined with the sensitivity and
speediness of the ion mobility spectrometry (IMS), provides an excellent
analytical tool for the fast detection and identification of NPS in bio­
logical fluids that can be used as vanguard methodology in clinical and
forensic cases.
2. Experimental
2.1. Standards, reagents and samples
Ethylphenidate, 4-fluoroethylphenidate, 4-methylmethylphenidate,
4-fluoromethylphenidate, were provided by the laboratory of the
Inspección de Farmacia y Control de Drogas (Valencia, Spain). Codeine,
benzocaine, lidocaine, and tetracaine were provided by Merck KGaA
(Darmstadt, Germany) and used to evaluate the selectivity of the syn­
thetized MIP.
Acetonitrile, 2-propanol, acetic acid glacial, and buffer constituents
were provided by Scharlab (Barcelona, Spain). Methanol was provided
by VWR (Leicester, England). Methacrylic acid (MAA), ethylene glicol
dimethacrylate (EGDMA), and azobisisobutryonitrile (AIBN) used for
polymer synthesis were purchased from Sigma (Steinheim, Germany).
Visiprep™SPE vacuum manifold and 1 mL empty poly-propylene
SPE cartridges with polyethylene frits (20 µm porosity) were obtained
from Supelco (Bellefonte, PA, USA).
Ethylphenidate-free oral fluid samples were collected from males
and females with ages ranging from 25 to 40 years old. Ethylphenidate
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Microchemical Journal 178 (2022) 107423
-free oral fluid samples were pooled and analyzed by the recommended
procedure to assess the absence of Ethylphenidate. After that, 1 mL
blank oral fluid samples were spiked with ethylphenidate at concen­
trations ranging from 120 to 480 µg L− 1. The ethylphenidate concen­
tration range has been selected taking into consideration the previously
published concentration of ethylphenidate in body fluids, the oral fluid-
to-plasma ratio of methylphenidate, and the toxic (lethal) levels for
methylphenidate that start from approximately 500 µg L− 1 in serum.
2.2. MIP synthesis
MIP was prepared by bulk polymerization using ethylphenidate as
template, MAA as monomer, EGDMA as cross-linker, acetonitrile as
porogen, and AIBN as initiator, in a molar ratio of template/monomer/
cross-linker ratio of 1:4:20. Firstly, 5.6 mg ethylphenidate was intro­
duced in a glass vial with 8.8 mg of MAA and both components were
dissolved in 130 µL of acetonitrile. The obtained solution was kept for 1
h in darkness at room temperature to allow template-monomer complex
formation. EGDMA cross-linker (79.1 mg) and AIBN initiator (2.5 mg)
were added to the template-monomer solution, and it was sonicated for
1 min and purged with a N2 stream for 1 min. After that, polymerization
mixture was introduced in a water bath at 60 ◦ C for 24 h.
The obtained polymer was washed with methanol, and, after
centrifugation, MIP was introduced in an oven at 60 ◦ C for 24 h. Polymer
was crushed and sieved (≤250 µm). Non-imprinted polymer (NIP) was
also prepared following the aforementioned procedure without the
template addition.
2.3. MIP characterization
MIP and NIP were characterized by scanning electron microscopy
(SEM) after a previous coating with an Au-Pt layer to increase material
conductivity. The morphological characterization was done by using a S-
4800 scanning electron microscope from Hitachi (Ibaraki, Japan) pro­
vided with an emission field gun, a secondary electron detector, and an
EMIP 3.0 acquisition data system from Rontec (Normanton, UK). Ni­
trogen adsorption–desorption isotherms were obtained at 77 K on a
Micromeritics (Norcross, GA, USA) ASAP-2020 automated instrument.
Specific surface areas were evaluated using the Brunauer-Emmett-Teller
(BET) method and the pore size distribution was calculated using the
Barrett–Joyner–Halenda (BJH) method.
Also, MIP and NIP were characterized by ATR-FTIR spectroscopy,
using a Tensor 27 spectrometer from Bruker (Bremen, Germany). It was
constituted by a DLaTGS detector and a Dura Sample IR II attenuated
total reflection (ATR) accessory for solid samples from Smiths Detection
Inc. (Warrington, UK) equipped with a one-reflection diamond/ZnSe
Dura Disk plate.
2.4. Extraction procedure
Empty polypropylene SPE tubes (1 mL) were filled with 25 mg MIP
or NIP, placed between two frits. Each SPE tube was washed with
methanol containing 10% (v/v) acetic acid until no template was
detected in the extract.
The extraction procedure implies cartridge conditioning with 1 mL 2-
propanol followed by 1 mL deionized water to remove the excess of
organic solvent. 1 mL sample was mixed with 0.5 mL phosphate buffer
(0.1 M, pH 7.0) and loaded onto the cartridge at a 2 mL min− 1 flow rate.
Washing step was performed with 1 mL deionized water containing
phosphate buffer (0.1 M, pH 7.0) and 2-propanol in a ratio 90:10 (v/v).
Cartridges were dried in the vacuum manifold for 5 min, and then 0.5
mL 2-propanol was used for the elution of ethylphenidate.
2.5. IMS analysis
NPS involved in this study were determined by IMS using an
P. García-Atienza et al.
IONSCAN-LS from Smiths Detection (Morristown, NJ, USA) with a 63Ni
foil radioactive source. Data acquisition and processing was done by
IMstation software (version 5.389) from Smiths Detection. Positive ion
mode was selected for measurements, using nicotinamide as internal
calibrant with a reduced mobility constant (K0) of 1.861 cm2 V− 1 s− 1.
Plasmagram acquisition was made using 30 ms scan period and a 0.2 ms
shutter grid width. A counter flow of dry air at 0.265 L min− 1 was used
as drift gas and drift region electric field was set at 251 V cm− 1.
3 µL sample extract was introduced by thermal desorption from a
polytetrafluoroethylene membrane using 1 s post-dispense delay. Tem­
peratures were adjusted to 255, 260, and 237 ◦ C for desorption, inlet,
and drift tube, respectively.
3. Results and discussion
3.1. MIP characterization
The morphology of synthesized MIP and NIP was characterized using
SEM and the results were depicted in Fig. 1a. Since bulk polymerization
was carried out, and the MIP or NIP were crushed and sieved, polymer
particles form agglomerated structures with irregular order. As it can be
seen, the size of MIP particles was lower than those found for the control
polymer (NIP). It suggested that the template compound has an
important influence on the material growth during the polymerization,
and consequently affecting the polymer microstructure. It could be
explained by strong interactions between functional monomer and
Fig. 1. SEM images at x50,000 magnification (a) and FTIR spectra (b) of MIP and NIP.
3
Microchemical Journal 178 (2022) 107423
template, which are responsible in assembling the components tightly
around the nucleation points, thus making the MIP particles smaller
[32,33]. In addition, the surface of MIP particles was rougher than that
of NIPs, which translates into a higher surface area; thus, facilitating the
mass transfer rate and the recognition ability of template molecule.
Further evidence of the higher surface area was confirmed by nitrogen
adsorption–desorption measurements. Thus, the BET analysis of MIP
showed significantly larger values (up to 93.2 m2 g− 1) in comparison to
that of the NIP (<5 m2 g− 1).
Also, FTIR measurements were done in order to confirm the correct
synthesis of materials. Fig. 1b shows ATR-FTIR spectra of MIP and NIP
polymers. The bands obtained were completely attributed to MAA-co-
EDMA-based polymeric material (1800 cm− 1 for carbonyl group, CH2
bending vibrations around 1405–1465 cm− 1, and C-O-C vibrations in
esters around 1240 and 1010–1040 cm− 1, approximately).
3.2. Evaluation of the MIP extraction conditions
Sample pH is a critical factor to be considered during SPE loading
step, because of ethylphenidate can interact through hydrogen bonds
and/or electrostatic interactions with the MIP. This interaction depends
on the pH of sample solution and pKa values of analytes. It has been
previously reported a pKa value ranging from 8.9 to 9.5 for methyl­
phenidate and 9.5 for ethylphenidate [34,35], whereas the pH of oral
fluid typically ranges from slightly acidic to slightly basic media, with
pH values from 5.5 to 7.9 [36]. On the other hand, the functional
P. García-Atienza et al.
monomer MAA has a pKa value of 4.7, being extensively used in the
extraction of basic analytes [27]. Taking into account these issues, and
to promote a proper interaction between the target analyte and the
MAA-based polymer, a phosphate buffer (0.1 M, pH 7.0) was used for
sample loading.
The washing step is another key parameter to obtain, at the same
time, maximum selectivity and recovery of ethylphenidate in MIP
extraction. Thus, 1 mL ethylphenidate standard solution of 250 µg L− 1 in
water was loaded in the SPE cartridges containing both MIP as well as
NIP particles. Water, and different mixtures of water:2-propanol were
evaluated as washing solvents. In all cases, cartridges were dried using
vacuum, and ethylphenidate was eluted with 1 mL 2-propanol.
Figure 2a shows that 15% (v/v) 2-propanol in water partially eluted
ethylphenidate from the MIP obtaining a recovery percentage of 60%,
while recoveries obtained after washing the MIP with water and 5 and
10% (v/v) 2-propanol in water were higher than 88%, whereas only a
50% ethylphenidate recovery was provided using SPE cartridges con­
taining NIP as sorbent.
In addition, different concentrations of 2-propanol in water from 0 to
15% (v/v) were also evaluated as washing solutions for the analysis of
ethylphenidate related molecules. As it can be seen in Fig. 2b, increasing
the concentration of 2-propanol in the washing solution from 0 to 15%
(v/v) provided a decrease in the recovery of 4-methyl methylphenidate
from 78 to 57%, while the rest of compounds (4-fluoroethylphenidate
and 4-fluoromethylphenidate) remained almost unaltered. Thus, 10%
(v/v) 2-propanol in water was selected as washing solvent for further
experiments, providing a quantitative recovery for ethylphenidate and
reducing potential interferences from other phenidate derivatives. Once
the SPE protocol was established, the imprinting factor was calculated as
the ratio of analyte retained in the MIP versus that retained in the NIP,
Fig. 2. Recovery obtained for the SPE of 1 mL ethylphenidate (a) and pheni­
date analogues (b) standard solutions at 250 µg L− 1 in water, using the pro­
posed MIP and different washing solutions.
4
Microchemical Journal 178 (2022) 107423
achieving a value of 2.3 for the target analyte, in front of 1.4 obtained for
4-methyl methylphenidate and 4-fluoroethylphenidate, and 0.9 for 4-
fluoromethylphenidate.
In order to increase the pre-concentration factor of the methodology,
different volumes of 2-propanol were studied as eluting solvent using
water spiked at 250 µg L− 1 ethylphenidate and the aforementioned
washing procedure. Ethylphenidate recoveries of 33 ± 2, 81 ± 2, and 99
± 3% were obtained for 0.25, 0.5, and 1.0 mL elution solvent, respec­
tively. Thus, 0.5 mL was selected as the most appropriate elution vol­
ume, since it provided a 2-fold pre-concentration factor, with
appropriate recoveries.
3.3. IMS determination of ethylphenidate in oral fluids
The obtained IMS plasmagram for a 250 µg L− 1 ethylphenidate
standard and an oral fluid spiked with ethylphenidate at 120 µg L− 1
extracted by the proposed procedure are shown in Fig. 3. As it can be
seen, the most intense peak at 9.57 ms drift time corresponded to
nicotinamide signal, the IMS internal calibrant with a reduced mobility
(K0) of 1.860 cm2 V− 1 s− 1, which was used to correct temperature and
pressure variations. Ethylphenidate showed a signal at 13.83 ms drift
time (K0 = 1.266 cm2 V− 1 s− 1), consistent with previously reported
values [37], which corresponds to the analyte molecular ion peak. Thus,
an alarm was generated in the IMS equipment to alert the presence of
ethylphenidate in the analysed oral fluid extracts, using the following
peak descriptors: (i) a K0 value of 1.266, (ii) a peak drift time variability
value of 0.05 ms, (iii) a minimum signal threshold value of 20, and (iv) a
200 μs full width value at the half-maximum amplitude of the peak.
The analytical features of the method were established using the
developed MIP sorbent for the SPE of ethylphenidate in combination
with IMS determination (see Table 1). Calibration curves were analyzed
from 66 to 600 µg L− 1 ethylphenidate, providing a good linearity (R2
greater than 0.998). The limits of detection (LOD) and quantification
(LOQ) were calculated as three and ten times the standard deviation of
the intercept divided by the slope of the calibration curve, giving values
of 20 and 66 µg L− 1, respectively. Precision was established as the
relative standard deviation of three determinations of a 100 µg L− 1
ethylphenidate standard in 2-propanol (n = 3), providing a value of 4%.
Method trueness was estimated as the recoveries obtained for the
analysis of blank oral fluid samples spiked with ethylphenidate at con­
centrations from 120 to 480 µg L− 1. The obtained recoveries are shown
in Table 2, with values ranging from 82 to 91%. As it can be seen, re­
coveries of ethylphenidate were quantitative in the studied concentra­
tion range, being useful for an easy and fast determination of
ethylphenidate in oral fluid samples.
Moreover, selectivity of the proposed MIP extraction procedure was
evaluated by the recovery obtained for phenidate analogues and other
psychoactive compounds, such as codeine, benzocaine, tetracaine and
lidocaine (Table 3). The obtained recoveries ranged from 30 to 68% for
phenidate analogues and from <LOD to 74% for the other psychoactive
compounds evaluated.
A comparison of the analytical features of the developed procedure
and those obtained from the previously published papers based on the
determination of ethylphenidate in biological fluids have been sum­
marized in Table 4. As it can be seen, all the precedents are based on the
use of LC-MS/MS due to the complexity of the analyzed sample and the
low concentration levels of ethylphenidate in biological samples. As it
can be seen, the LOD obtained using the developed procedure (20 µg
L− 1) is higher than those obtained by LC-MS/MS. Regarding the sample
treatment used in those scientific papers, it can be highlighted the liq­
uid–liquid extraction using organic solvents and also the SPE by means
of generic sorbents. The use of MIP sorbents in SPE provides the addi­
tional selectivity to the IMS measurements required to compete with
selectivity provided by the LC-MS/MS analysis. Moreover, the acquisi­
tion cost of the instrumentation is substantially lower and, as an addi­
tional advantage, the IMS based procedure could be easily adapted to
P. García-Atienza et al. Microchemical Journal 178 (2022) 107423

1 1
Fig. 3. IMS signals obtained for a 250 µg L− ethylphenidate standard (a) and an oral fluid spiked with ethylphenidate at 120 µg L− extracted by SPE using the
proposed MIP.

Table 1 Table 4
Analytical features of ethylphenidate determination by IMS. Analytical features of the published articles regarding ethylphenidate determi­
Analytical feature Value
nation in biological fluids.
− 1 Sample Sample Analytical LOD RSD Reference
Linear range (µg L ) 66–600
treatment technique (µg (%)
Linearity (R2) 0.998
L− 1)
Slope (L µg− 1) 0.250 ± 0.002
Intercept (µg L− 1) 0.9 ± 1.2 Post SPE (Strata LC-MS/MS 5 15 [14]
RSD (%, n = 3) 4 mortem Screen C),
LOD (µg L− 1) 20 femoral evaporation to
LOQ (µg L− 1) 66 blood dryness
Rat plasma LLE (75:25, v/v, UFLC-MS/ 1 1.5–6.7 [15]
ethyl acetate: MS
acetonitrile)
Table 2 Human LLE (4:1, v/v, LC-MS/MS 0.025 5.6–7.5 [16]
Recoveries obtained for the analysis of field saliva samples spiked at different plasma butyl chloride:
concentration levels of ethylphenidate by using the developed MIP-IMS acetonitrile)
procedure. Oral fluid SPE (CEREX Clin LC-MS/MS 0.5 11–12 [19]
II), evaporation
[Spiked] (µg L− 1) [Found] (µg L− 1
± s, n = 3) Recovery (% ± s) to dryness
120 109 ± 8 91 ± 7 Oral fluid SPE (MIP) IMS 20 4 This
300 252 ± 6 84 ± 2 study
480 374 ± 20 82 ± 4
Abbreviations: IMS, ion mobility spectrometry; LC, liquid chromatography; LLE,
liquid–liquid extraction; LOD, limit of detection; MIP, molecularly imprinted
polymer; MS, mass spectrometry; MS-MS, tandem mass spectrometry; RSD,
Table 3 relative standard deviation; SPE, solid-phase extraction; UFLC, ultra-fast liquid
Recoveries obtained for the analysis of water samples spiked at 250 µg L− 1 chromatography.
ethylphenidate, phenidate analogues, and potential interferents by using the
developed MIP-IMS procedure. terms of selectivity, sensitivity, and precision. Good sensitivity and
Compound [Found] (µg L− 1
± s, n = 3) Recovery (% ± s) selectivity have been achieved, while the reproducibility of the devel­
Ethylphenidate 245 ± 13 98 ± 5 oped method can be classified as satisfactory. Results shown that MIP
4-fluoroethylphenidate 152 ± 5 61 ± 2 sorbent certainly contributed to the matrix clean-up and the selectivity-
4-methylmethylphenidate 170 ± 15 68 ± 6 enhanced extraction of the target compound. Moreover, the non-specific
4-fluoromethylphenidate 75 ± 7 30 ± 3 adsorption of other undesired compounds is substantially reduced. The
Codeine 90 ± 10 35 ± 4
Benzocaine <LOD –
method, based on IMS determination, showed quantitative recoveries in
Tetracaine 130 ± 10 52 ± 4 oral fluid samples, from 82 to 91%, and LOD and LOQ of 20 and 66 µg
Lidocaine 187 ± 12 74 ± 5 L− 1, respectively.
a
LOD for benzocaine was set at 15 µg L− 1.
The novelty of this study lies in the few research reported to date
concerning the selective isolation of NPS using MIPs and their analysis
by IMS. The development of new methodologies for the analysis of oral
“in-field” measurements.
fluids allows the identification of the parent compounds instead of their
respective metabolites, which significantly reduces potential mis­
4. Conclusions
identifications in routine control of other biological matrices as, for
example, urine.
A simple and practical method for the synthesis of a MIP sorbent for
the selective SPE of ethylphenidate in oral fluids has been described. The
extracting features of the synthesized sorbent have been validated in

5
P. García-Atienza et al.
CRediT authorship contribution statement
P. García-Atienza: Methodology, Validation, Investigation, Writing
– original draft. F.A. Esteve-Turrillas: Conceptualization, Methodol­
ogy, Validation, Investigation, Resources, Supervision, Funding acqui­
sition, Writing – review & editing. S. Armenta: Conceptualization,
Methodology, Validation, Investigation, Resources, Supervision, Fund­
ing acquisition, Writing – review & editing. J.M. Herrero-Martínez:
Conceptualization, Methodology, Validation, Investigation, Resources,
Supervision, Funding acquisition, Writing – review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgements
Authors gratefully acknowledge the financial support of the projects
(PID2019-110788GB-I00 and RTI2018-095536-B-I00) funded by MCIN/
AEI/10.13039/501100011033 and by “ERDF A way of making Europe”
by the European Union.
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