Molecularly imprinted polymers as selective adsorbents for ambient plasma mass spectrometry
Anal Bioanal Chem
Molecularly imprinted polymers as selective adsorbents for ambient plasma mass spectrometry
Micha? Ceg?owski 0 1 2
Marek Smoluch 0 1 2
Edward Reszke 0 1 2
Jerzy Silberring 0 1 2
Grzegorz Schroeder 0 1 2
0 Micha? Ceg?owski
1 Department of Biochemistry and Neurobiology, Faculty of Materials Science and Ceramics, AGH University of Science and Technology , Al. Mickiewicza 30, 30-059 Krako?w , Poland
2 Faculty of Chemistry, Adam Mickiewicz University in Poznan , Umultowska 89b, 61-614 Poznan? , Poland
The application of molecularly imprinted polymers (MIPs) as molecular scavengers for ambient plasma ionization mass spectrometry has been reported for the first time. MIPs were synthesized using methacrylic acid as functional monomer; nicotine, pr opyphenazone, or methylparaben as templates; ethylene glycol dimethacrylate as a cross-linker; and 2,2?-azobisisobutyronitrile as polymerization initiator. To perform ambient plasma ionization experiments, a setup consisting of the heated crucible, a flowing atmospheric-pressure afterglow (FAPA) plasma ion source, and a quadrupole ion trap mass spectrometer has been used. The heated crucible with programmable temperature allows for desorption of the analytes from MIPs structure which results in their direct introduction into the ion stream. Limits of detection, linearity of the proposed analytical procedure, and selectivities have been determined for three analytes: nicotine, propyphenazone, and methylparaben. The analytes used were chosen from various classes of organic compounds to show the feasibility of the analytical procedure. The limits of detections (LODs) were 10 nM, 10, and 0.5 ?M for nicotine, propyphenazone, and methylparaben, respectively. In comparison with the measurements performed for the non-imprinted polymers, the values of LODs were imp r o v e d f o r a t l e a s t on e o r d e r o f m a g n i t u d e d u e t o preconcentration of the sample and reduction of background noise, contributing to signal suppression. The described procedure has shown linearity in a broad range of concentrations. The overall time of single analysis is short and requires ca. 5 min. The developed technique was applied for the determination of nicotine, propyphenazone, and methylparaben in spiked real-life samples, with recovery of 94.6-98.4%. The proposed method is rapid, sensitive, and accurate which provides a new option for the detection of small organic compounds in various samples.
Molecularly imprinted polymers; Ambient plasma mass spectrometry; Selective adsorption; Molecular scavengers; Flowing atmospheric pressure afterglow
Functional polymers form a wide group of materials that
possess unique physicochemical properties. They find numerous
applications in various areas, such as drug delivery [
], catalysis [
], water purification [
preparation of membranes , and stimuli-responsive polymers [
Molecularly imprinted polymers (MIPs) form a unique group
of functional polymers due to their antibody-like affinity.
They are obtained during copolymerization of the functional
monomers and cross-linkers in the presence of template
molecules. After removal of the templates, MIPs possess
recognition cavities that are complementary to the template molecules
in terms of shape, size, and location of functional groups. In
contrary to the natural antibodies, MIPs show many
outstanding advantages, such as high chemical stability,
excellent reusability, relatively easy, reproducible, and low-cost
]. As a result, MIPs have been widely used as
artificial receptors for separation purposes, as sensors, to
promote catalysis, during drug development and for screening
]. One of the most widely used application of MIPs is
solid-phase extraction (SPE). SPE is one of the most
popular sample pretreatment methods nowadays, because it
allows for the concentration and isolation of an analyte
from various complex matrices [
]. The high affinity
and selectivity of MIPs is ideally suited for their
applications in SPE [
Ambient ionization mass spectrometry (ambient MS)
comprises a group of various techniques, which allows for MS
analysis of various samples at atmospheric pressure. They
provide rapid, direct, and high-throughput analyses with no
or only minimal sample pretreatment. Moreover, substances
can be analyzed directly from surfaces or other matrices [
Plasma-based techniques, particularly direct analysis in
realtime (DART) [
], flowing atmospheric-pressure afterglow
], low-temperature plasma (LTP) [
dielectric barrier discharge ionization (DBDI) [
], and various
types of microplasma [
], form a unique group among
ambient MS techniques. They involve the generation of a direct
current or radiofrequency electrical discharge between a pair
of electrodes in contact with a flowing inert gas, creating a
stream of ionized molecules, radicals, excited state neutrals,
and electrons. The obtained plasma species are directed
towards the sample, thus resulting in desorption and ionization
of the analytes. Ambient plasma MS techniques have the
advantages due to their simple instrumentation, rugged
construction, absence of solvents, and generation of singly charged
analyte species that are easily identifiable than
multiplecharged ions and various adducts produced by the
spraybased techniques [
The combination of spray-based ambient MS and MIPs
films glued to the stainless steel probe has been reported by
Figueiredo et al. [
]. The researchers described the use of
an easy, ambient sonic-spray ionization mass spectrometry
(EASI-MS) for the analysis of phenothiazines extracted
from the urine by MIPs. Van Biesen et al. have reported the
use of desorption electrospray ionization-mass
spectrometry (DESI-MS) coupled with thin-film MIPs for selective
extraction and quantification of 2,4-dichlorophenoxyacetic
In this study, MIPs selective towards nicotine, propyphenazone,
and methylparaben (template molecules used for MIPs synthesis)
were obtained. The analytes used were chosen from
various classes of organic compounds to show the feasibility
of the analytical procedure. The physicochemical
properties and adsorption characteristics of the obtained MIPs
were examined. After adsorption of particular analytes,
MIPs were transferred to the programmably heated crucible,
which allowed for thermal desorption of these compounds.
The vapors obtained during thermal desorption were directly
ionized and analyzed using FAPA mass spectrometry. In
contrary to other published designs, we have not used
MIPs films but conventional, bulk MIPs. To the best of
our knowledge, this is the first study describing a combination
of MIPs and plasma-based ambient mass spectrometry. The
advantage of using bulk MIPs over MIPs films is the
possibility to introduce more analyte to the plasma source which
can improve sensitivity of the analytical method.
Materials and methods
Chemicals and reagents
All reagents used were commercial products. Methacrylic
acid, ethylene glycol dimethacrylate (EGDMA),
2,2?azobisisobutyronitrile solution (0.2 M in toluene), nicotine,
propyphenazone, and methylparaben were obtained from
Sigma-Aldrich (St. Louis, MO, USA). All solvents were of
the p.a. grade, obtained from Avantor Performance Materials
Poland S.A. (Gliwice, Poland) and were used without further
Urine and plasma samples
Drug-free urine samples used for the experiments involving
real-life samples were obtained from the laboratory staff
volunteers. Human plasma samples were obtained from
SigmaAldrich (St. Louis, MO, USA).
The surface morphology of the polymer particles was
examined using the scanning electron microscope (SEM, Hitachi
S3000N, Hitachi Co., Ltd., Tokyo, Japan). The FT-IR (Fourier
transform infrared) spectra were obtained using the Nicolet iS
50 FT-IR spectrometer (Thermo Scientific, Waltham, MA,
USA). UV?vis measurements were made with the aid of an
Agilent 8453 (Santa Clara, California, US) spectrophotometer
using 1-cm plastic cuvettes. Mass spectra were obtained using
the NOVA011 (ERTEC, Wroclaw, Poland) FAPA ambient
plasma source combined with a Bruker Esquire 3000 ion trap
mass spectrometer (Bruker Daltonics, Bremen, Germany).
The experimental details of the plasma ion source were
described in our previous publications [
Synthesis of MIPs and NIPs
All molecularly imprinted polymers were synthesized using the
procedure which has been proven to result in a synthesis of
water-compatible, molecularly imprinted polymers [
Firstly, 1 mmol of the template (nicotine, propyphenazone, or
methylparaben) and 4 mmol of methacrylic acid were dissolved
in 20 mL chloroform in a glass pressure tube. The solution was
sonicated and purged with nitrogen for 30 min. Afterwards,
20 mmol EGDMA and 2 mL 2,2?-azobisisobutyronitrile
solution (0.2 M in toluene) were added. The tube was sonicated and
purged with nitrogen for 10 min, sealed, and placed in an oven
for 18 h at 60 ?C. After polymerization, the polymer was dried
under reduced pressure, grounded using mortar and pestle, and
sieved using a 60-mesh sieve. The removal of template
molecules from MIPs was accomplished through a Soxhlet
extraction. A sample of MIPs was placed inside the cellulose
extraction thimble. The extraction solvent was a mixture of ethanol
and acetic acid (9:1 v/v). The extraction was continued for 24 h,
whereas the heating power was adjusted to allow the solvent to
cycle every 30 min. Afterwards, the Soxhlet extraction was
repeated using pure ethanol as an extraction solvent.
Finally, the materials obtained were dried under reduced
pressure. As a result, three MIPs were obtained: imprinted
with nicotine (denoted as MIP(nic)), propyphenazone
(MIP(prph)), and methylparaben (MIP(mpb)). The exemplary
scheme of synthesis using nicotine as a template molecule is
presented in Fig. 1. The schemes of synthesis using
propyphenazone and methylparaben as template molecules
have been presented in Electronic Supplementary Material
(ESM) Figs. S1 and S2, respectively. A non-imprinted
Fig. 1 Scheme of MIP(nic)
polymer (NIP) was synthesized similarly to the MIPs but
without the use of template molecules.
The adsorption of nicotine, propyphenazone, or methylparaben
on the corresponding MIPs and NIP was examined using batch
experiments. To prepare adsorption isotherms, a series of
samples containing 5 mg of an appropriate MIPs or NIP was
equilibrated with 2 mL solution containing various
concentrations (0.01?1 mM) of nicotine, propyphenazone, or
methylparaben. The solution was shaked at room temperature
for 24 h. After adsorption, the mixture was isolated by
centrifugation and examined with UV?vis spectrophotometer at
261 nm for nicotine, 266 nm for propyphenazone, and
256 nm for methylparaben. The precise concentration of all
analytes was measured by plotting calibration curves. The
adsorption amount (qe; mg g?1) was calculated from the
where C0 and Ceq are the initial and equilibrium
concentrations (mg L?1), m is the sorbent mass (g), and V is the
solution volume (L).
For the adsorption kinetic studies, 5 mg of an appropriate
MIPs or NIP and 2 mL of solution containing nicotine,
propyphenazone, or methylparaben at the initial concentration
of 0.1; 0.01, and 0.05 mM, respectively, were stirred at room
temperature. The concentration of analytes was measured at
preset time intervals using UV?vis spectrophotometer. The
amount of adsorbed material at time t, qt (mg g?1) was
Fig. 3 SEM images of a leached
MIP(nic), b non-leached
MIP(nic), and c NIP
where m is the sorbent mass (g), C0 is the initial concentration, Ct
is the concentration at time t (h), and V is the solution volume (L).
To prepare MIPs and NIP for FAPA-MS experiments,
10 mg of MIPs or NIP were shaken at room temperature in
10 mL water solution of an appropriate analyte in a broad
range of concentrations (from 5 nM to 1 mM) for 12 h.
Afterwards, MIPs and NIP were isolated by centrifugation
and decantation of the supernatant. One milligram of each
polymer was subsequently transferred to the FAPA-MS
Experiments involving the real life samples were
performed by spiking urine or plasma with appropriate analytes
(0.05?5 ?M). The urine was spiked with nicotine [
], as these compounds are excreted from
the human body in a free form. The plasma was spiked with
propyphenazone. This substance can be found in a free form
in the plasma only and is excreted from the human body as
various biotransformation products [
]. To adsorb analytes
from these samples 5 mg of the appropriate MIPs or NIP were
shaken at room temperature in 5 mL of spiked urine or
plasma sample. Afterwards, MIPs and NIP were isolated
by centrifugation and decantation of the supernatant. One
milligram of each polymer was subsequently transferred
to the FAPA-MS setup.
Fig. 4 Adsorption isotherms of a
nicotine, b propyphenazone, and
c methylparaben on the
corresponding MIPs and NIP
The photograph of the FAPA-MS setup is shown in Fig. 2.
The setup consists of a FAPA ion source (Fig. 2a), a heated
mini crucible allowing programmable heating in the range of
50?480 ?C (Fig. 2b) and the inlet to the mass spectrometer
(Fig. 2c). The FAPA ion source was positioned on the axis of
the inlet of the mass spectrometer with the tip located ca.
50 mm from the MS inlet. The mini crucible allowing
temperature-controlled desorption was placed ca. 10 mm
below the ion stream. One milligram of each polymer was placed
in a mini crucible and heated from room temperature to ca.
350 ?C with a temperature ramp rate of 3 ?C s?1. The vapors
generated in such way were directly introduced into the
plasma jet stream, which resulted in their ionization. The mass
spectrometer was operating in the positive ion mode during
analysis of nicotine or propyphenazone and in the negative ion
mode during analysis of methylparaben. The overall average
time of analysis was ca. 5 min. For the experiments performed
with solutions of the analytes, 10 ?L of the appropriate
solution were introduced into the mini crucible and heated to ca.
Results and discussion
The exemplary SEM images of MIP(nic), MIP(nic) before
removal of the template, and NIP are presented in Fig. 3a?c,
respectively. All polymer particles have rough surfaces,
whereas the distribution of particle sizes is in the range of
0.1?0.4 ?m. There are no visible differences in the morphology
of MIPs with or without template molecules and NIP.
SEM images of MIP(prph) and MIP(mpb) before and
after removal of template molecules are presented in
Fig. S3 (ESM).
All materials (MIPs with and without template and NIP)
display similar characteristic peaks in IR spectra, indicating
that the backbone structure of all polymers is similar. The O?H
Parameters of analyte adsorption by MIPs and NIP
stretching and bending vibrations of carboxyl groups are at
3544 and 1389 cm?1, respectively. The symmetric and
asymmetric ester C?O stretching vibrations are at 1250
and 1142 cm?1, respectively. The stretching vibration of
C=O bonds are at 1723 cm?1, whereas asymmetric
stretching vibrations of CH2 groups are at 2955 cm?1
]. MIPs with template molecules (non-leached)
show additional bands characteristic for a particular template:
MIP(nic) with nicotine show additional signals at 2779
and 716 cm?1; MIP(prph) with propyphenazone show
additional signals at 1655, 754, and 698 cm?1; MIP(mpb)
with methylparaben show additional signals at 1682 and
Adsorption properties of MIPs
Adsorption isotherms were used to characterize the adsorption
properties of MIPs and NIP at the equilibrium state. Figure 4
presents the relationships between the equilibrium
concentration of the analytes and the amount of compounds adsorbed on
MIPs or NIP. The adsorption capacities decrease with
decreasing initial analyte concentration, which is a result of the lower
mass transport coefficient. To describe the adsorption process,
Langmuir and Freundlich adsorption isotherm models were
The Langmuir adsorption isotherm was applied in the
Ceq Ceq 1
qeq ? qm ? Kqm
where K (L mg?1) is the binding equilibrium constant, qm
(mg g?1) is the maximum amount of the analyte adsorbed,
Ceq (mg L?1) is the analyte equilibrium concentration, and
qeq (mg g?1) is the amount of an analyte adsorbed at the
concentration Ceq. The calculated values of qm, K, and correlation
coefficients (R2) are given in Table 1. The R2 values obtained
for adsorption of the corresponding analytes on MIPs are in
the 0.950?0.965 range, which indicates that the experimental
data only partially fits the Langmuir adsorption model. On the
other hand, the R2 values obtained for adsorption on NIP are in
Fig. 5 Relationship between
time and the adsorption amount
for adosprtion of a nicotine, b
propyphenazone, and c
methylparaben on the
corresponding MIPs and NIP
the range between 0.970 and 0.987 implying that the data fit
the Langmuir adsorption model better than in the case of
MIPs. This difference can be explained by the assumptions
made in the Langmuir model, particularly that the adsorbed
substance forms a monolayer on a completely homogenous
surface of the adsorbent. Both MIPs and NIP do not possess
completely homogenous surfaces; however, in the case of
MIPs, the polymer possesses additional cavities formed
during polymerization in the presence of the template. The
presence of the cavities is responsible for an increased
inhomogeneity of the structure of the adsorbent, reflected by lower R2
values. The qm values calculated for experiments performed
with particular analytes are at least two times higher for MIPs
than for NIP. This result clearly indicates that MIPs can absorb
more analyte due to distinct imprinting process. The obtained
values of qm are in accordance with data obtained for other
molecularly imprinted polymers [
]. The comparison of
binding equilibrium constants (K parameters) obtained for
MIPs and NIP also suggests an excellent imprinting effect,
which is a result of a presence of specific binding sites within
the structure of MIPs.
The Freundlich adsorption isotherm is mathematically
qeq ? K f Ce1q=n
logqeq ? logK f ? n logCeq
where Kf and n represent the Freundlich constants, Ceq
(mg L?1) is the analyte equilibrium concentration, and qeq
(mg g?1) is the amount of analyte adsorbed at the
concentration Ceq. The calculated values of Kf, 1/n, and correlation
coefficients (R2) are given in Table 1. The R2 values obtained
for adsorption of corresponding analytes on MIPs are in the
0.994?0.999 range which clearly indicates that the Freundlich
isotherm model agrees very well with the experimental data.
The Freundlich adsorption model assumes non-ideal
adsorption on a heterogeneous surface characterized by uniform
]. Due to these assumptions, this model is more
adequate in characterization of analyte adsorption on MIPs. The
structure and surface of NIP is more homogenous due to the
lack of recognition cavities; therefore, R2 values calculated for
the Freundlich adsorption model are slightly lower than those
of MIPs and are in the 0.989?0.993 range.
The change in adsorption capacity with interaction time
(Fig. 5) was studied to characterize the kinetics of adsorption.
Two kinetic models were applied to examine the mechanism
of adsorption process. The first model was the
pseudo-firstorder model given by Langergren and Svenska which is
mathematically expressed as:
log?qe?qt? ? log qe? 2:303
where qe and qt are the amounts of analyte adsorbed (mg g?1)
at equilibrium and at time t (h), respectively, and k1 (h?1) is the
rate constant. The second model applied was the
pseudosecond-order equation based on the equilibrium adsorption
which can be expressed as:
t 1 1
qt ? k2qe2 ? qe
where k2 (g mg?1 h?1) is the rate constant of second-order
adsorption. The calculated k1, k2, and R2 values are presented
in Table 2. The R2 values obtained for pseudo-first-order
model are relatively small providing that this model is inapplicable
to describe the adsorption of analytes on MIPs or NIP. On the
contrary, R2 values obtained for pseudo-second-order model
are higher than 0.991 for all MIPs and NIP that clearly
indicates that this model is applicable to describe kinetics of the
adsorption process. The k2 rate constants obtained for
adsorption of corresponding analytes on MIPs are for all tested
substances higher than those obtained for adsorption on NIP. This
result shows that adsorption on MIPs is more favorable than
adsorption on NIP.
The combination of MIPs and ambient plasma mass
spectrometry was achieved by in situ thermal desorption
Kinetic parameters calculated for pseudo-first-order and pseudo-second-order models
Fig. 6 Relationship between
average EIC area obtained during
FAPA-MS analysis of a MIP(nic)
and nicotine concentration, b
MIP(prph) and propyphenazone
concentration, and c MIP(mpb)
and methylparaben concentration
carried in a heated mini crucible. The vapors generated
during this process contained an analyte adsorbed by
MIPs. Thermal desorption was conducted up to
350 ?C, which resulted in decomposition of the
polymer. In all experiments, the extracted ion
chromatograms (EIC) of the ions corresponding to nicotine
([M + H]+ at m/z 163), propyphenazone ([M + H]+ at
m/z 231), and methylparaben ([M ? H]? at m/z 151)
have been obtained to exclude ions generated during
polymer decomposition. EIC was integrated and the
averages of five measurements were used for subsequent
calculations. The results of FAPA-MS experiments
obtained with the use of MIPs, NIPs, and pure solution of
analytes have been compared. Blank experiments were
conducted using leached MIPs and NIP and were
repeated ten times. The relative standard deviation
(RSD) obtained for all data did not exceed 20%. The
limit of detection (LOD) was calculated in accordance
with the definition: LOD = mean blank value + 3 ?
standard deviation. The LODs computed for nicotine were
10 nM for MIP(nic), 5 ?M for NIP, and 10 ?M for
nicotine solution. For propyphenazone LODs were
0.5 ?M for MIP(prph), 5 ?M for NIP, and 10 ?M for
propyphenazone solution. For methylparaben, LODs
were 0.1 ?M for MIP(mpb), 5 ?M for NIP, and 50 ?M
for methylparaben solution. In comparison with the
measurements performed for analytes, MIPs improve LOD
for at least two orders of magnitude and for at least one
order of magnitude in comparison with NIP. The highest
improvement in LOD was observed for nicotine,
particularly in comparison with nicotine solution. MIP(nic) had
LOD improved by three orders of magnitude, whereas for
NIP, LOD was improved by two orders of magnitude.
The graphical presentation of the LOD data is presented
in Figs. S4 to S12 (ESM).
The described procedure has shown linearity in a broad
range of concentrations. The experiments performed using
MIP(nic) indicated linearity within the range of 0.1 to
10 ?M of nicotine (R2 = 0.997). MIP(prph) displayed
linearity within the range of 0.5 to 10 ?M of propyphenazone
(R2 = 0.986). MIP(mpb) revealed linearity within the
range of 0.1 to 10 ?M of methylparaben (R2 = 0.992).
The graphs presenting the relationship between the analyte
concentration and an average area obtained after EIC
integration for MIP(nic), MIP(prph), and MIP(mpb) are
shown in Fig. 6. The lack of linearity at higher
concentrations is presumably caused by the saturation either of the
ion trap (excess of ions) or MIPs (saturated capacity of the
To evaluate the selectivity of the MIPs, MIP(prph) and
MIP(mpb) were immersed in a mixture of their analytes and
compounds structurally related to them. MIP(prph) (10 mg)
was added to a solution of propyphenazone (1 ?M) and
Results of selectivity experiments of MIPs and NIP
phenazone (1 ?M). During FAPA-MS analysis, EIC of the
ions corresponding to these compounds ([M + H]+) have
been recorded. Similarly, MIP(mpb) (10 mg) was added to a
solution of methylparaben (1 ?M), ethylparaben (1 ?M), and
butylparaben (1 ?M). During FAPA-MS analysis, EIC of the
ions corresponding to these compounds ([M ? H]?) have been
recorded. Identical set of experiments was performed with the
use of NIP. All EICs have been integrated, and the quotients
obtained by dividing the areas calculated for the analytes by
areas of compounds structurally related to them are given in
Table 3. In both experiments involving the use of MIPs, a clear
increase in selectivity towards the analyte molecules can be
observed. This indicates that MIPs show an increased affinity
towards target molecules and selectively interact with them.
Analysis of real samples
To validate the performance of the proposed method for
determination of nicotine, propyphenazone, and methylparaben
in the real-life samples, urine and plasma samples were
analyzed and the results obtained are collected in Table 4. To
evaluate the applicability of the analytical results, urine and plasma
samples were spiked with the analytes at various
concentrations. Quantification was done using appropriate MIPs in
combination with FAPA-MS analysis. The resulting recovery
values (94.6?98.4%) show good performance of the proposed
combination of MIPs and FAPA-MS and confirm that this
method can be applied for the analysis of various analytes in
the real-life samples.
Comparison with other analytical methods
Comparison with other methods
To show the performance of the proposed combination of
MIPs and FAPA-MS, the technique has been compared to
other previously reported methods for determination of
nicotine, propyphenazone, and methylparaben in terms of LOD and
linearity (Table 5). The developed method has lower LOD and
improved linearity than other reported techniques used for
detection and quantification of nicotine or propyphenazone. In
comparison with procedures used for detection and
quantification of methylparaben, the developed setup has lower LOD
than pulse voltammetry, however, higher than an ultrahigh
performance liquid chromatography-tandem mass spectrometry
coupled with dispersive liquid-liquid microextraction [
The latter method is time-consuming as compared to the
5-min analysis time.
In summary, we have shown that molecularly imprinted
polymers can be effectively used as selective adsorbents prior to
the analysis by ambient plasma mass spectrometry. Synthesis
of the MIPs is simple, involves low-cost reagents, and results
in the structures that possess high adsorption properties
combined with good selectivity. A simple setup with heating
system with programmable temperature allows for thermal
desorption of the analytes from MIPs to be directly introduced
into FAPA ion stream. The developed method offers rapid
analysis, improved LOD over other analytical methods, and
linearity for broad range of concentrations. The estimated
limits of detection clearly indicate that the presented analytical
procedure allows for detection of organic compounds at very
low concentrations, making such technique also suitable for
diagnostic purposes. The developed method is a destructive
analytical technique, as the MIPs undergo thermal
decomposition; therefore, their reuse in not possible. Taking into
account the low cost of their synthesis, this issue can be
considered as minor. The combination of MIPs and FAPA-MS has
proven to be effective in analysis of real-life samples such as
the urine and plasma. Further improvement of these limits of
detection by using MS/MS analysis or single ion monitoring is
currently in progress in our laboratory.
Acknowledgements This work was supported by the National Science
Centre, Poland, under grant number 2016/21/B/ST4/02082.
Compliance with ethical standards The authors declare that the
studies have been approved by the Bioethics Committee: BKomisja Bioetyczna
przy Uniwersytecie Medycznym im. Karola Marcinkowskiego^
(resolution no. 937/16) and have been performed in accordance with the ethical
The approved document by the Bioethics Committee requires an
informed consent from all volunteers who participated in the study. The
authors declare therefore that all volunteers have signed an informed
consent for allowing the use of provided urine samples in this study.
Conflict of interest The authors declare that they have no conflict of
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