Application of novel copper organic material for facile microextraction of sodium valproate from human plasma samples: Experimental design optimization and isotherm study

Article abstract of DOI:10.1002/aoc.3960

Well-designed metal organic materials (MOMs) were synthesized and applied for pre-concentration and determination of sodium valproate (Na-VP) from biological samples, bound to the copper complex of 1,4-phenylenedioxydiacetic acid under mild conditions. The channels of this sorbent provide high efficiency and also selectivity. The MOMs were structurally characterized using Fourier transform infrared and energy-dispersive X-ray spectroscopies, scanning electron microscopy and X-ray diffraction, and they were found to have suitable features for quantification of Na-VP using HPLC coupled with UV detection at λ?=?215?nm. Moreover, the rate of adsorption is improved by ultrasonic power and the experimental data are best fitted according to Freundlich adsorption isotherm. According to the central composite design, the best experimental conditions are 280.0?μl, 3.0?min and 17.0?mg for volume of eluent, sonication time and sorbent mass respectively. Calibration plots show linear responses towards Na-VP concentrations (0.4–18.0?μg ml^?1), satisfactory limit of detection (0.06?μg ml^?1, S/N?=?3) and reasonable enrichment factor (70.58). The coefficient of variation values of both inter- and intra-day analyses were less than 4.0%, indicating a candidate method for the determination of Na-VP in human plasma with reasonable recovery and efficiency.

Full text of DOI:10.1002/aoc.3960

Received: 15 February 2017
DOI: 10.1002/aoc.3960
Revised: 3 May 2017
Accepted: 17 June 2017
F U L L P A P E R
Application of novel copper organic material for facile
microextraction of sodium valproate from human plasma
samples: Experimental design optimization and isotherm
study
Sonia Bahrani1 | Mehrorang Ghaedi1
| Tahere Taghipour1 |
Mohammad Javad Khoshnood Mansoorkhani2 | Ahmad Reza Bagheri1 | Abbas Ostovan3
1 Department of Chemistry, Yasouj
Well‐designed metal organic materials (MOMs) were synthesized and applied
for pre‐concentration and determination of sodium valproate (Na‐VP) from bio-
logical samples, bound to the copper complex of 1,4‐phenylenedioxydiacetic
acid under mild conditions. The channels of this sorbent provide high efficiency
and also selectivity. The MOMs were structurally characterized using Fourier
transform infrared and energy‐dispersive X‐ray spectroscopies, scanning elec-
tron microscopy and X‐ray diffraction, and they were found to have suitable
features for quantification of Na‐VP using HPLC coupled with UV detection
at λ = 215 nm. Moreover, the rate of adsorption is improved by ultrasonic
power and the experimental data are best fitted according to Freundlich adsorp-
tion isotherm. According to the central composite design, the best experimental
conditions are 280.0 μl, 3.0 min and 17.0 mg for volume of eluent, sonication
time and sorbent mass respectively. Calibration plots show linear responses
towards Na‐VP concentrations (0.4–18.0 μg ml−1), satisfactory limit of detection
(0.06 μg ml−1, S/N = 3) and reasonable enrichment factor (70.58). The coeffi-
cient of variation values of both inter‐ and intra‐day analyses were less than
4.0%, indicating a candidate method for the determination of Na‐VP in human
plasma with reasonable recovery and efficiency.
University, Yasouj 75918‐74831, Iran
2 Department of Pharmacology Toxicology,
Faculty of Pharmacy, Shiraz University of
Medical Sciences, Shiraz, Iran
3 Department of Chemistry, Kerman
Branch, Islamic Azad University, Kerman,
Iran
Correspondence
Mehrorang Ghaedi, Chemistry
Department, Yasouj University, Yasouj
75918‐74831, Iran.
Email: m_ghaedi@mail.yu.ac.ir;
m_ghaedi@yahoo.com
Funding information
Graduate School and Research Council of
the University of Yasouj
KEYWORDS
1,4‐phenylenedioxydiacetic acid, biological sample, Freundlich isotherm, metal organic material,
sodium valproate, ultrasound power
1 | INTRODUCTION
neurotransmitter in the human brain.[3] It stabilizes brain
electrical activity by diminishing gamma‐aminobutyric
Sodium valproate (sodium 2‐propylpentanoate, Na‐VP) as
an anticonvulsant has a notable influence on treatment of
partial seizures,[1] control of epilepsy and non‐general
mood changes.[2] Its structure is different from that of
most of the other antiepileptic drugs which is believed to
affect the function of the gamma‐aminobutyric acid
acid metabolism[1b] and also it has a high potential for
the treatment of the acute manic phase of bipolar disorder
and prophylaxis migraine headaches.[4] Valproate deriva-
tive neurological effects are proportional to the amounts
in the blood. Thus, quantification of valproate in epileptic
patients is a key for controlling sudden attacks of epilepsy,
Appl Organometal Chem. 2017;e3960.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 9
https://doi.org/10.1002/aoc.3960

2 of 9
BAHRANI ET AL.
while therapeutic drug monitoring in pharmacokinetic
studies is done by various analytical methods.[5] In this
regard, analyses of valproate compounds in drug formula-
tions and/or biological samples are carried out using var-
ious separation protocols including GC,[6] liquid
chromatography–mass spectrometry[7] and HPLC
coupled with UV,[8] diode array,[9] fluorescence[6,10] or
evaporative light scattering[11] detection. In most cases,
the presence of low concentrations of analyte in a compli-
cated matrix strongly limits the performance of an analyt-
ical method. Here, a primary powerful pre‐concentration
technique, solid‐phase microextraction (SPME), helps in
improving figures of merit of a method.[12] To this end, a
new class of solid crystalline materials called metal
organic materials (MOMs) have attracted the attention
of a number of researchers.[13] In a definitive sense,
MOMs include the distinctive porous compounds
possessing metal centre(s) bonded to organic linkers
(molecular bridging ligands) and accordingly via a molec-
ular building block approach it is possible to design
MOMs with different pore sizes and dimensions.[14]
MOMs exhibit diverse compositions in comparison to
inorganic porous materials such as zeolitic aluminosili-
cates and aluminophosphates.[15] MOMs offer many prop-
erties including high thermal stability, large accessible
uniform pores and extra‐large surface area.[16] In this
case, these features afford opportunities for applications
in gas storage/separation,[17,14a] luminescence,[18] magne-
tism,[19] catalysis,[20] lithium ion batteries[21] and pre‐con-
centration of heavy metal ions.[22] Thus, MOMs simply
applied for efficient sorption of analytes and subsequent
ultrasonic‐assisted SPME are recommended in separation
with distinct advantages like simplicity, low cost and min-
iaturization for small‐volume samples. The cavitation
appearing following ultrasound supplies higher surface
areas in order to accelerate the release of interesting
analytes and to improve method efficiency.[23] Response
surface methodology has an extensive applicability for
achieving reliable optimum points which enables the best
prediction of behaviour.[24]
purchased from Merck (Darmstadt, Germany) and were
used without further purification. Analytical gradient
grade HPLC solvents were obtained from Merck
(Darmstadt, Germany) and filtered with a 0.22 μm hydro-
phobic polytetrafluoroethylene membrane. Ultrapure
water was produced by a Milli‐Q system (Millipore,
Bedford, MA, USA) and then filtered with a 0.2 μm
Whatman ME membrane. A stock standard solution of
Na‐VP (10 mg l−1) was prepared in methanol and working
solutions were prepared daily by diluting the stock solu-
tion. Blood plasma samples were provided by Fars Blood
Transfusion Center (Shiraz, Fars, Iran).
2.2 | Instrumentation
X‐ray diffraction (XRD; Philips PW 1800) measurements
of the samples were carried out using Cu Kα radiation
(40 kV and 40 mA). The morphology of photocatalyst
sample was investigated using scanning electron micros-
copy (SEM; KYKY‐EM3200) under an accelerating volt-
age of 26 kV. Energy‐dispersive X‐ray spectrometry
(EDS) was conducted using an Oxford INCA II (Oxford
Instruments, UK) energy solid‐state detector. Fourier
transform infrared (FT‐IR) spectra of compounds were
recorded with a JASCO‐680 instrument in the range
400–4000 cm−1 using KBr pellets with a ratio of 1:100
for samples to KBr. The pH was adjusted using a pH/ion
meter (model 686, Metrohm, Switzerland). An ultrasonic
bath equipped with a heating and degassing system (Elma
Sonic S30H GmbH) operating at a frequency of 40 kHz
with a power of 130 W was used for the ultrasound‐
assisted adsorption procedure. A Sigma super‐speed
refrigerated centrifuge model 3 K30 (B. Braun) was used
to accelerate phase separation. Statistica software version
10.0 (Stat Soft Inc., Tulsa, USA) was used to generate the
central composite design (CCD) matrices as well as the
analysis of data.
2.3 | HPLC analysis
In the study reported here, the efficiency of extraction
of Na‐VP in human plasma samples was investigated by
ultrasound‐assisted SPME. Search and design were con-
ducted of novel material as a good choice to improve the
figures of merit corresponding to the sorption system.
HPLC experiments were performed using an Adept
series gradient HPLC system (Milton Technical Centre,
Cambridge, UK) equipped with PowerStream software
and interface system manager (CE4900), UV–visible
detector (CE4200), duel piston pumps (CE4104), in‐line
vacuum solvent degasser (CE4040), sample injection
valve with a 20 μl sample loop and a Macherey Nagel
Nucleosil‐C18 (4.6 mm i.d., 250 mm, 5 μm) column
operating at a wavelength of 215 nm. Data were col-
lected and analysed using PowerStream software. The
mobile phase consisted of water–acetonitrile (50:50 v/v;
pH = 3.5) at a flow rate 1.0 ml min−1. The system
was operated at ambient temperature.
2 | EXPERIMENTAL
2.1 | Chemicals and materials
Na‐VP (≥98%) and copper chloride dihydrate
(CuCl2⋅2H2O) were purchased from Sigma‐Aldrich. Other
chemical materials with the highest purity were

BAHRANI ET AL.
3 of 9
the mixture by vortex for 2.0 min and subsequent immer-
sion in an ultrasonic bath for 3.0 min to reach equilibrium
(complete extraction of analyte). Furthermore, efficient
phase separation the sample was achieved by centrifuga-
tion (5000 rpm, 10.0 min). The solution was then
decanted and adsorbed analytes were eluted by 280.0 μl
of methanol (as eluent solvent), while 20.0 μl of this solu-
tion was injected into the HPLC‐UV system for further
analysis.
2.4 | Synthesis of MOM
2.4.1 | Synthesis of 1,4‐
phenylenedioxydiacetic acid (1,4‐BDOAH2)
A mixture of hydroquinone (2.75 g) and chloroacetic acid
(7.1 g) was prepared and subsequently NaOH solution
(48 g in 97.5 ml of water) was added dropwise to this mix-
ture and heated in an oil bath to 80°C. The mixture was
stirred for 1.5 h and subsequently was cooled to room
temperature and in the next stage the solution was kept
in an ice bath for 30 min. Then, HCl (37% w/w) was added
dropwise to the solution until neutral pH. On cooling the
reaction flask to room temperature and filtering, a white
precipitate of 1,4‐BDOAH2 was obtained which was
2.7 | Adsorption procedure
Na‐VP has acidic functional groups that simply react with
sorbent via strong electrostatic interaction and/or hydro-
gen bonding that enables accumulation and pre‐concen-
tration of Na‐VP. The amount of Na‐VP binding to
MOM sorbent was calculated by adding 25.0 mg of
MOM into a tube containing 50 ml of Na‐VP solution with
various concentrations in the range 10.0–80.0 μg ml−1
with pH adjusted to 3.5. The mixture was dispersed using
an ultrasonic bath for 3.0 min at room temperature and
the analysis was performed by HPLC‐UV. The adsorption
capacity for Na‐VP, Q (mg g−1), was calculated using the
following equation[25]:
1
washed with cold water. H NMR (D2O, 250 MHz, δ,
ppm): 4.34 (s, 4H), 6.81 (s, 4H). 13C NMR (D2O,
62.9 MHz, δ, ppm): 67.24, 115.42, 152.12, 147.7, 177.02.
2.4.2 | Synthesis of cu‐1,4‐BDOAH2
1,4‐BDOAH2 (2.2 mmol) was dissolved in 50 ml of deion-
ized water by sonication and in the next stage mixed thor-
oughly with a 0.13 M solution of CuCl2⋅2H2O in deionized
water. The mixture was vigorously stirred at room tem-
perature for 15 min which led to the formation of a light
blue precipitate. The solution was filtered and the precip-
itate was washed with cold water.
ðCi−CeÞV
Q ¼
(1)
m
where Ci and Ce are respectively the initial and equilib-
rium concentration of Na‐VP, V is the total volume of
the solution and m is the MOM dosage.[26]
2.5 | Preparation of plasma sample
In order to survey the performance of the optimized pro-
posed procedure for a complicated real sample, enrich-
ment of Na‐VP was carried out from a human plasma
sample. For this purpose, 10.0 ml of plasma sample was
collected into a centrifuge tube and mixed thoroughly
with 20.0 ml of acetonitrile followed by centrifuging at
5000 rpm for 10 min to precipitate proteins. The clear
supernatant solution was diluted to 10.0 ml with distilled
water and the sample pH was adjusted to 3.5 (optimum
pH value). Then, the extraction procedure described in
the next section was done according to the analysis of
Na‐VP by standard addition method. All real samples
were filtered using a 0.22 μm syringe filter (Millipore,
Bedford, MA, USA) prior to HPLC analysis.
3 | RESULTS AND DISCUSSION
3.1 | Characterization of MOM
The FT‐IR spectra of 1,4‐BDOAH2 and Cu‐1,4‐BDOAH2
in the range 450–4000 cm−1 (Figure 1a) show a large
broad band in the range 2000–3400 cm−1 which is
assigned to the stretching vibrations of the acidic O―H
group. The absorption band at 1400–1600 cm−1 is related
to the C¼C vibration. The absorption band at 1220 cm−1
is attributed to the stretching vibrations of C―O while
bands at 1058 cm−1 are assigned to O―C¼O symmetric
and asymmetric stretching vibrations as well as the C―O
stretching vibration. The bands at 684 and 813 cm−1 are
related to aromatic C―H bending.[27]
2.6 | Ultrasound‐assisted SPME procedure
When the acid is converted to the copper complex, a
The enrichment process of Na‐VP from a sample was car-
ried out as follows: 17.0 mg of MOM sorbent was dis-
persed into Na‐VP solution with known concentration at
pH = 3.5 in a centrifuge tube. The best dispersion of sor-
bent in the mixture was achieved following agitation of
band attributable to νsym(OCO) appears in the region
1320–1345 cm−1 [28]
The reaction of the organic linker
.
with Cu2+ is associated with a shift of absorption bands
corresponding to O―H, C¼O and O―C¼O groups,
strongly supporting successful synthesis of the target

4 of 9
BAHRANI ET AL.
FIGURE 1 (a) FT‐IR spectra and (b) and XRD pattern of the
synthesized MOM
compound, while its identity was confirmed by further
characterizations.
The XRD pattern of Cu‐1,4‐BDOAH2 (Figure 1b) does
not show any diffraction peaks at 35°, 38°, 49°, 53°, 58°
and 62° related to the CuO lattice planes of (110), (111),
(202), (020), (202) and (113), respectively.[29] Moreover,
the pattern does not match up with Cu2O peaks at 30°,
36°, 42° and 62° corresponding to (110), (111), (200) and
(220) crystal planes,[30] indicating that the synthesized
sample is not CuO or Cu2O. However, it strongly agrees
with the XRD pattern of Cu‐1,4‐BDOAH2 which is com-
posed of distinct peaks at 2θ of 11°, 13°, 15°, 16°, 17°,
20°, 24° and 26° which perfectly match up with (222),
(400), (331), (422), (511), (600), (551) and (731) crystal
planeof Cu compound, respectively.[31]
FIGURE 2 (a) SEM image and (b) elemental composition as
deduced by EDS of MOM
concentration to reach an equilibrium state. The adsorp-
tion capacity of MOM can be calculated by fitting the
experimental data to an isotherm model.[32]
3.2.1 | Freundlich isotherm
The Freundlich adsorption equation can be applied to fit
the experimental data as follows[33]:
A typical SEM image of Cu‐1,4‐BDOAH2 (Figure 2a)
confirms the rose‐like surface morphology of the sample.
In Figure2 (b), the EDS spectrum of Cu‐1,4‐BDOAH2 is
shown. This indicates the presence of C, O and Cu in
the Cu‐1,4‐BDOAH2 sample.
logQ ¼ logα þ m logCe
(2)
where Q (mg g−1) is the amount of adsorbed analyte per
unit of nanosorbent mass, Ce (mg l−1) is the concentration
of analyte, while m and α are Freundlich constants.
Furthermore, Figure 1Sb shows that the amount of
Na‐VP adsorbed on MOM was high (87.1 mg g−1) which
confirmed the performance of the sorbent for determina-
tion of Na‐VP.
3.2 | Adsorption isotherm
Adsorption isotherm models including Freundlich and
Langmuir isotherms can be used to evaluate the experi-
mental equilibrium data. As illustrated in Figure 1Sa,
the adsorption capacity increased with Na‐VP

BAHRANI ET AL.
5 of 9
3.2.2 | Langmuir isotherm
3.3.2 | Eluent solvent composition
The Langmuir linear equation is expressed in the follow-
ing form:
The selection of an appropriate eluent solvent is very
important for a desorption process to achieve good recov-
ery and high pre‐concentration factor for the target com-
pound applied. In this regard, the applicability of
various solvents including acetonitrile, methanol, ethanol
and n‐hexane was studied for elution of pre‐concentrated
Na‐VP. The results (Table 1).showed that owing to its
higher solvating power compared to the other solvents,
methanol leads to the achievement of the highest extrac-
tion recovery. The influence of the volume of eluent on
extraction recovery was also investigated by subsequent
experimental design.
Ce
1
Ce
¼
þ
(3)
Qe KaQm Qm
The values of Qm and Ka, respective correlation coeffi-
cients, indicate knowledge about the Langmuir model
constant. Qm is 64.8 mg g−1 of adsorbent, exhibiting rele-
vant adsorption properties (Figure 1Sc).
3.3 | Optimization of extraction procedure
To ensure advancing the optimization approach, the
influence of some variables like solvent and composition
of eluent and pH of Na‐VP solution on the extraction pro-
cess was initially investigated using univariate method
and subsequently following adjustment of their optimum
value depending on response to variables like the volume
of eluent, sonication time and sorbent dosage were opti-
mized by CCD.
3.3.3 | Analysis of design of experiment
CCD was created to find the main factors affecting the
extraction efficiency with the fewest experiments.[34] In
this design, three independent variables, namely sorbent
dosage (X1), volume of eluent (X2) and sonication time
(X3), at five levels (Table 1S) were examined and their
main and combined effects influence the analysis of vari-
ance (ANOVA). The mathematical relationship of extrac-
tion recovery to significant terms was represented by a
second‐order polynomial equation.[35]Regarding the
3.3.1 | Influence of pH on response
The influence of pH on adsorption of Na‐VP onto MOM
was investigated in the range 2.0–9.5. Figure 3 reveals that
the best recovery is achieved at acidic pH, and a greater
value, owing to probable change in structure of Na‐VP
and appearance of negative charge onto sorbent, leads to
the generation of repulsive force which hinders more
accumulation of analyte onto MOM. On the other hand,
at acidic pH, probably due to an abundance of neutral
form of valproate, stronger attraction between analyte
and sorbent leads to more accumulation of analyte onto
sorbent.
TABLE 1 Effect of type of eluent on extraction recovery of Na‐VP
Eluent solvent
ER%
MeCN
77.82
EtOH
86.46
97.47
49.79
MeOH
n‐hexane
FIGURE 4 Standardized (P = 0.05) Pareto chart, representing the
estimated effects of parameters obtained from the CCD. Vertical line
in the chart defines the 95% confidence level
FIGURE 3 Na‐VP recoveries from MOM as function of
solution pH

6 of 9
BAHRANI ET AL.
experimental results of the response surface regression
procedure, the best fitted model equation was achieved
by the following second‐order polynomial equation:
than 0.05 (95% confidence interval) that indicates their
non‐significant contribution to performance of Na‐VP
recovery in the system under study. Furthermore, Pareto
charts (P = 95%) are other criteria which prove and con-
firm the significant influences of variables (Figure 4)
results of which have good agreement with ANOVA
results. The F value (10.36) and P value (0.09) of ‘lack of
fit’ confirm the suitability of the model for predicting the
behaviour of the extraction process (Figure 2Sa) and lin-
ear relationship between experimental and theoretical
value of ER% is established and confirms normal distribu-
tion error around the mean. Plot of residuals versus
observed values (Figure 2Sb) indicates the model
adequacy.
ER%Na‐VP ¼ 93:232 þ 3:693X1−0:242X21−0:662X2 (4)
þ0:001X22 þ 6:238X3 þ 0:634X23
þ0:032X1X2−0:355X1X3−0:356X2X3
From equation 4, the relationship between recovery of
Na‐VP and independent factors in the coded unit (X1, X2,
X3) is determined.
As was found from ANOVA data (Table 2S), the p‐
values of all parameters except X2, X22 and X32 were more
FIGURE 5 Three‐dimensional response surfaces and contour diagrams showing the effects of the mutual interactions between two
independent variables: (a) eluent volume–adsorbent mass; (b) ultrasonication time–adsorbent mass; (c) ultrasonication time–eluent volume

BAHRANI ET AL.
7 of 9
Generally, a three‐dimensional response surface rep-
increased with MOM dosage due to high surface area and
nanosize of sorbent. Approximately the intermediate
amount of sorbent (17.0 mg) was enough to achieve satis-
factory recovery. Investigating the effect of eluent volume
on the ER% of Na‐VP (Figure 5c) demonstrated that 180 μl
of eluent is required to desorb the optimum amount of
Na‐VP from the sorbent thoroughly. As seen in Figure 5
a, the combined effects of sorbent mass and eluent vol-
ume on the ER% reveal that the eluent solvent can be
applied to a small quantity of sorbent, while the use of
too much sorbent in the solid phase reduces the
dispersibility of the eluent volume and increases the diffi-
culty of recovery.
resents the effect of each pair of variables involved in
the pre‐concentration process (Figure 5). Figure 5(b,c)
shows that sonication time in the range 2.7–9.3 min has
a strong effect on response and system. High pressure var-
iation induced during ultrasonic irradiation can enhance
diffusion coefficient and increase the contact between
analyte and sorbent, leading to achievement of maximum
recovery. The best Na‐VP recovery was achieved in short
sonication time (3.0 min) and the system reached equilib-
rium very quickly. The effect of amounts of sorbent on the
Na‐VP pre‐concentration (Figure 5b) reveals that recovery
The desirable profile for all variables to get highest
recovery (Figure 3S) reveals that maximum response
was observed at 17.0 mg of sorbent, 280.0 μl of eluent vol-
ume and 3.0 min sonication time.
3.4 | Analytical figures of merit
One of the most important pre‐concentration processes is
its calibration curve which is simply achieved following
extraction and enrichment of analyte over a wide concen-
tration range for conditions optimized previously. Experi-
mental results which are presented in Figure 6 show that
a linear response over 0.4–18.0 μg ml−1 with satisfactory
coefficient of determination (R2 > 0.999) was obtained.
The limit of detection (LOD = 3Sb/m) and limit of quanti-
fication (LOQ = 10Sb/m) were defined based on three and
ten times signal‐to‐noise ratios, where m is the calibration
sensitivity and Sb is the standard deviation of blank.
Acceptable LOD (0.06 μg ml−1) and LOQ (0.19 μg ml−1
)
confirmed the applicability of this method. Within‐day
precision was tested at three distinct concentration levels
of Na‐VP, namely 0.7, 8.0 and 15.0 μg ml−1. Moreover,
between‐day precision was investigated and checked at a
concentration of 8.0 μg ml−1. The relative standard devia-
tions (RSDs) of both repeatability and reproducibility stud-
ies (n = 3) were below 5.0%. On the other hand, the
enrichment factor value was calculated as the ratio of cali-
bration slope after and before pre‐concentration. A
FIGURE 6 (a) calibration curve for adsorption of Na‐VP on
MOM after pre‐concentration. (b) standard curve extracted from
plot data
TABLE 2 Characteristic data for determination of Na‐VP by the proposed method
Regression equation after pre‐concentration
y = 47448x + 64849, R2 = 0.999
Linear range (DLR; μg ml−1
Limit of detection (LOD; n = 10; μg ml−1
)
0.4–18.0
)
0.06
Limit of quantification (LOQ; n = 10; μg ml−1
)
0.19
Enrichment factor
70.58
Repeatability intra‐day, RSD (n = 3)
Reproducibility inter‐day, RSD (n = 3)
(8.0 μg ml−1
)
(0.7 μg ml−1
)
(8.0 μg ml−1
)
(15.0 μg ml−1
)
3.8%
2.3%
3.2%
3.4%

8 of 9
BAHRANI ET AL.
reasonable enrichment factor (EF = 70.58) of the method
was found. The useful analytical data including LOD,
LOQ, RSD and EF are listed in Table 2. The results indicate
the suitability of the proposed method for detecting pre‐
concentrated Na‐VP from biological samples.
REFERENCES
[1] a) T. S. Belal, D. S. El‐Kafrawy, M. S. Mahrous, M. M. Abdel‐
Khalek, A. H. Abo‐Gharam, Spectrochim. Acta A 2016, 155,
47; b) M. Nestic, S. Babic, D. M. Pavlovic, D. Sutlovic, Forensic
Sci. Int. 2013, 231.
[2] P. Norouzi, S. Shirvani‐Arani, P. Daneshgar, M. R. Ganjali,
Biosens. Bioelectron. 2007, 22, 1068.
3.5 | Analysis of real sample
[3] M. Zarejousheghani, P. Fiedler, M. Möder, H. Borsdorf, Talanta
2014, 129, 132.
The feasibility of proposed microextraction method was
demonstrated by applying the current method to a pre-
pared plasma sample. The quantity of spiked Na‐VP in
plasma sample was evaluated by standard addition
method. The respective chromatogram plots are presented
in Figure 4Sa,b. An average value of 10.46 μg ml−1 was
obtained for Na‐VP in the plasma sample, which is in
good agreement with the value spiked (10.5 μg ml−1). This
indicates that the proposed procedure is qualified for the
analysis of Na‐VP in biological samples.
[4] a) J. Tonic‐Ribarska, A. Haxhiu, Z. Sterjev, G. Kiteva, L.
Suturkova, S. Trajkovic‐Jolevska, Acta Pharma. 2012, 62, 211.
b) T. O0Donnell, S. Rotzinger, M. Ulrich, C. C. Hanstock, T. T.
Nakashima, P. H. Silverstone, Eur. Neuropsychopharmacol.
2003, 13, 220.
[5] B. Mohammadi, M. B. Majnooni, P. M. Khatabi, R. Jalili, G.
Bahrami, J. Chromatogr. B 2012, 880, 12.
[6] H. R. Sobhi, A. Kashtiaray, H. Farahani, F. Abrahimpour, A.
Esrafili, Drug Test. Anal. 2010, 2, 362.
[7] a) L. Yuan, J. Ma, M. Ding, S. Wang, X. Wu, Y. Li, K. Ma, X.
Zhou, F. Li, Food Chem. 2011, 131, 1063; b) D. S. Jain, G.
Subbaiah, M. Sanyal, P. Shrivastav, Talanta 2007, 72, 80; c) F.
Fernández‐Campos, A. Calpena, D. Soy, H. Colom, J. Liq.
Chromatogr. Relat. Technol. 2012, 35, 1171.
4 | CONCLUSIONS
The present study is based on the development of simple,
fast and efficient method for the synthesis of nanosized
copper organic material as an efficient solid phase for
Na‐VP pre‐concentration of human plasma samples.
SEM, EDS and XRD analyses confirmed its high purity
and nanosized structure. Some of the main points were
considered in the synthesis of MOM including mild condi-
tions, time‐consuming and high adsorption capacity,
which means it can be employed as an excellent sorbent.
CCD was used as a high‐efficiency tool to optimize the
efficiency of key factors singly and in combination in an
extraction process to improve the performance character-
istics and minimize the error of experiments. The opti-
mized ultrasound‐assisted SPME HPLC‐UV method
manifested outstanding recovery, reasonable LOD, low
inter‐day and intra‐day precision values with the achieve-
ment of a pre‐concentration factor of 70.58 which are
good criteria, indicating that the presented MOM has suit-
able potential in the pre‐concentration of Na‐VP from
human plasma samples.
[8] H. Amini, M. Javan, A. Ahmadiani, J. Chromatogr. B 2006, 830,
368.
[9] P. R. S. Souza, J. M. Carvalho, A. L. M. Albert, J. C. Moreira, K.
C. Leandro, Vigilância Sanitária em Debate 2013, 1.
[10] Y. Zhong, Z. Jiao, Y. Yu, Biomed. Chromatogr. 2006, 20, 319.
[11] M. K. Manoj Babu, J. Pharm. Biomed. Anal. 2004, 34, 315.
[12] M. Arabi, M. Ghaedi, A. Ostovan, J. Tashkhourian, H.
Asadallahzadeh, Ultrason. Sonochem. 2016, 33, 67.
[13] a) J. Chakraborty, I. Nath, F. Verpoort, Coord. Chem. Rev. 2016,
326, 135; b) X. Liu, C. Wang, Z. Wang, Q. Wu, Z. Wang,
Microchim. Acta 2015, 182, 1903.
[14] a) T. Pham, K. A. Forrest, B. Tudor, S. K. Elsaidi, M. H.
Mohamed, K. McLaughlin, C. R. Cioce, M. J. Zaworotko, B.
Space, Langmuir 2014, 30, 6454; b) M. R. Sohrabi, Z. Matbouie,
A. A. Asgharinezhad, A. Dehghani, Microchim. Acta 2013, 180,
589.
[15] Z. Zhang, L. Zhang, L. Wojtas, P. Nugent, M. Eddaoudi, M. J.
Zaworotko, J. Am. Chem. Soc. 2012, 134, 924.
[16] a) K. A. Forrest, T. Pham, A. Hogan, K. McLaughlin, B. Tudor,
P. Nugent, S. D. Burd, A. Mullen, C. R. Cioce, L. Wojtas, M. J.
Zaworotko, B. Space, J. Phys. Chem. C 2013, 117, 17687; b) Q.
Wu, S. Cheng, C. Wang, X. Li, Z. Li, C. Hao, Microchim. Acta
2016, 183, 3009.
ACKNOWLEDGEMENTS
The authors express their appreciation to the Graduate
School and Research Council of the University of Yasouj
for financial support of this work.
[17] a) L. J. Murray, M. Dinca, J. R. Long, Chem. Soc. Rev. 2009, 38,
1294; b) C. E. Wilmer, O. K. Farha, T. Yildirim, I. Eryazici, V.
Krungleviciute, A. A. Sarjeant, R. Q. Snurr, J. T. Hupp, Energy
Environ. Sci. 2013, 6, 1158.
[18] M. D. Allendorf, C. A. Bauer, R. K. Bhakta, R. J. Houk, Chem.
Soc. Rev. 2009, 38, 1330.
ORCID
[19] D. F. Weng, Z. M. Wang, S. Gao, Chem. Soc. Rev. 2011, 40, 3157.
[20] L. Ma, C. Abney, W. Lin, Chem. Soc. Rev. 2009, 38, 1248.
Mehrorang Ghaedi http://orcid.org/0000-0001-8282-895X
Abbas Ostovan http://orcid.org/0000-0002-1154-7760

BAHRANI ET AL.
9 of 9
[21] G. Li, H. Yang, F. Li, F. Cheng, W. Shi, J. Chen, P. Cheng, Inorg.
Chem. 2016, 55, 4935.
[33] M. Arabi, M. Ghaedi, A. Ostovan, Microchim. Acta 2017, 184,
879.
[34] M. Arabi, M. Ghaedi, A. Ostovan, J. Chromatogr. B 2017, 1048,
[22] M. Taghizadeh, A. A. Asgharinezhad, M. Pooladi, M. Barzin, A.
102.
Abbaszadeh, A. Tadjarodi, Microchim. Acta 2013, 180, 1073.
[35] M. Ghaedi, F. N. Azad, K. Dashtian, S. Hajati, A. Goudarzi, M.
[23] M. Arabi, M. Ghaedi, A. Ostovan, S. Wang, J. Colloid Interface
Sci. 2016, 480, 232.
Soylak, Spectrochim. Acta A 2016, 167, 157.
[24] M. Arabi, M. Ghaedi, A. Ostovan, ACS Sustain. Chem. Eng.
2017, 5, 3775.
SUPPORTING INFORMATION
[25] M. Arabi, M. Ghaedi, A. Ostovan, Food Chem. 2016, 210, 78.
Additional Supporting Information may be found online
in the supporting information tab for this article.
[26] M. Arabi, A. Ostovan, M. Ghaedi, M. K. Purkait, Talanta 2016,
154, 526.
[27] S. E. Mousavinia, S. Hajati, M. Ghaedi, K. Dashtian, Phys.
Chem. Chem. Phys. 2016, 18, 11278.
How to cite this article: Bahrani S, Ghaedi M,
Taghipour T, Mansoorkhani MJK, Bagheri AR,
Ostovan A. Application of novel copper organic
material for facile microextraction of sodium
valproate from human plasma samples:
Experimental design optimization and isotherm
study. Appl Organometal Chem. 2017;e3960.
https://doi.org/10.1002/aoc.3960
[28] X. Song, J. Li, J. Wang, L. Chen, Talanta 2009, 80, 694.
[29] J. Zhu, D. Li, H. Chen, X. Yang, L. Lu, X. Wang, Mater. Lett.
2004, 58, 3324.
[30] S. Jiao, L. Xu, K. Jiang, D. Xu, Adv. Mater. 2006, 18, 1174.
[31] B. Sun, S. Kayal, A. Chakraborty, Energy 2014, 76, 419.
[32] F. Zare, M. Ghaedi, A. Daneshfar, S. Agarwal, I. Tyagi, T. A.
Saleh, V. K. Gupta, Chem. Eng. J. 2015, 273, 296.