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Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342

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Journal of the Taiwan Institute of Chemical Engineers


journal homepage: www.elsevier.com/locate/jtice

Electrocatalytic effect of uoroapatite in reducing paracetamol at


carbon paste electrode: Analytical application
Y. EL Bouabi a, A. Farahi a,b, M. Achak c, M. Zeroual a, K. Hnini a, S. El Houssame a,
M. Bakasse d, A. Bouzidi a, M.A. El Mhammedi a,
a
Univ Hassan 1, Laboratoire de Chimie et Modlisation Mathmatique, 25 000 Khouribga, Morocco
b
Universit Ibn Zohr, Facult de Sciences, BP 8106 Cit Dakhla, Agadir, Morocco
c
Ecole Nationale des Sciences Appliques, Laboratoire des Sciences de lIngnieur Pour lEnergie, Universit Chouaib Doukkali, El Jadida, Morocco
d
Laboratoire de Chimie Organique Bioorganique et Environnement, Facult de Sciences, Universit Chouaib Doukkali, Morocco

a r t i c l e i n f o a b s t r a c t

Article history: A carbon paste electrode modied with uoroapatite (FAPCPE) was examined to catalyze the electro-
Received 13 December 2015 chemical reduction of paracetamol (PCT). The FAPCPE has demonstrated an ecient performance to-
Revised 26 May 2016
ward PCT reduction compared to that obtained using unmodied carbon electrode. The electrochemical
Accepted 15 June 2016
behavior of PCT has been investigated and the optimum experimental conditions were achieved. More-
Available online 29 June 2016
over, a good linear relationship was achievable over the concentration range from 4.0 108 mol/L to
Keywords: 1.0 103 mol/L using square wave voltammetry (SWV). The detection limit (S/N = 3) was also calculated
Fluoroapatite and a low value of 1.25 108 mol/L was obtained with 210 s of accumulation time. The effect of coex-
Square wave voltammetry isting of interferent compounds such as ascorbic acid (AA), citric acid (CA) and a binary mixture with
Paracetamol dopamine (DA) was also investigated. The proposed method was successfully applied to PCT determina-
Water tion in natural waters, tablets and urine samples with the results agreeing with independently veried
Tablets
HPLC.
Urine
2016 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

1. Introduction The review of literature for the assessment of PCT either indi-
vidual or in combined dosage form reveals that a number of meth-
Drug analysis plays a major role in the quality control of drug ods have been reported based on various analytical techniques.
formulations which has great health risks. A simple, sensitive and Those established methods include capillary electrophoresis (CE)
accurate method to determine the active ingredients in drugs [5], high performance liquid chromatography (HPLC) [68], HPLC-
seems essential [1]. tandem mass spectrometry [9], TLC [10], UV-spectrophotometry
Paracetamol (acetaminophen) is one of the important drug hav- [11,12], titrimetry [13], spectrouorometry [14], colorimetry [15],
ing antipyretic and analgesic properties most frequently prescribed Fourier transform infrared spectrometry [16] and thermogravimet-
throughout the world. It has been proved to be extremely e- ric analysis (TGA) [17]. However, although the analysis of PCT has
cient for the mild pain relief, muscular aches, neuralgia, migraine been extensively studied, to our knowledge few works based on
headache, rheumatic pain, fever and osteoarthritis [2]. electrochemical methods using modied electrodes have been de-
In general, PCT seems to be safe and appears to have no toxic veloped [1820]. In addition, the electrochemical methods are very
effects on humans health when taken in normal therapeutic doses simple, highly sensitive and low apparatus cost than other tradi-
[3]. However, taking high doses of PCT may cause adverse effects in tional methods [21]. It is noteworthy, that the modied electrodes
the body, although in proper doses it does not display any side ef- show a high sensitivity and selectivity toward the determination of
fects. Nowadays, PCT is widely used for its remarkable therapeutic PCT [22,23] than the unmodied ones [24].
characteristics thus precise determination and control of its quality The low biodegradability of PCT motivates us to develop the re-
is vital [4]. dox methods favoring its electrochemical activity. Indeed, the elec-
trocatalytic reduction or oxidation can be advantageously applied
to the extensive treatment of real matrices to detect and eliminate
PCT. Consequently, a suitable catalyst is of great interest in real ap-
plications and it can be used to accelerate the reduction of PCT

Corresponding author. Tel.: +212 68858296; fax: +212 23485201. with a signicant increase of the reduction currents and a shift of
E-mail address: elmhammedi@yahoo.fr, elmhammedi@gmail.com (M.A. El
potentials towards less negative values.
Mhammedi).

http://dx.doi.org/10.1016/j.jtice.2016.06.013
1876-1070/ 2016 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
34 Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342

Fig. 1. (A) CVs of 1.0 104 mol/L PCT on the (a) CPE and (b) FAPCPE at scan rate of 50 mV/s in 0.1 mol/L PBS (pH 7.0). (B) Square wave voltammograms of 1.0 104 mol/L
PCT in 0.1 mol/L PBS at (a) CPE and (b) FAPCPE (FAP/CP of (6/4: w/w).

Continuing with our interest in the use of uoroapatite (FAP) as 2.3. Preparation of the chemically modied electrode
a carbon paste modied electrodes having sensing probes toward
the oxidation or reduction of various electroactive species [25,26]. The modied carbon-paste electrode was prepared by mixing
Among the different inorganic solids, FAP has advantages because the graphite powder with the uoroapatite to give a ratio FAP/CP
it is cheap, readily available, stable in water, non-toxic, not a pollu- of (6/4 : w/w). Portions of the resulting composite material were
tant and, in particular, the uorapatite is reputed unanimously for then packed into a home built electrode assembly consisting of the
their weak solubility [27], herein we report an ecient and per- cavity (geometric area 0.1256 cm2 ) of PTFE cylindrical tube elec-
tinent method for the electroreduction of PCT using square wave trode of a plastic pipette tip. Electrical contact was established
voltammetry. This methodology has been successfully applied to with a bar of carbon.
construct an enhanced sensing platform for the electrochemical
detection of PCT in natural water samples, commercial tablets and 2.4. Electrochemical measurements
human urines without any sample pre-purication steps.
A glass cell was washed with 10% hydrochloric acid then rinsed
with DBW. Two-step procedures were followed for the analyt-
2. Experimental ical determination of PCT in aqueous samples. At open circuit,
the working electrode was rst immersed in 0.1 mol/L phosphate
2.1. Reagents buffer solution (PBS) containing PCT. Where the accumulation of
PCT was achieved chemically, the square wave experiments were
All chemicals used were of analytical grade or of the high- performed in PBS electrolyte solutions at FAPCPE. The potential
est purity available. FAP [28], sodium hydroxide, sodium phos- range was performed from 0.0 mV to 500 mV with a frequency of
phate dibasic, monosodium phosphate and chloridric acid were 30 Hz, pulse height of 40 mV and modulation amplitude 5 mV at
purchased from commercial sources and used as received. scan rate 150 mV/s. The cyclic voltammogram was recorded be-
Paracetamol (Malinkroute, 99.99%) was dissolved in phos- tween 0.4 and 1.0 V. EIS was performed between 100 kHz and
phate buffer solution (0.1 mol/L) to prepare stock solutions of 100 mHz at AC amplitude of 10 mV. All measurements were per-
1.0 103 mol/L. Then the working standard solutions were pre- formed at room temperature.
pared by successive dilution of the stock solutions by sodium sul-
fate. Carbon paste was supplied from Carbone, Lorraine, ref 9900, 2.5. HPLC analysis of paracetamol
France. All the reagents used were of analytical grade. Distilled wa-
ter (DW) was used throughout the preparation of the solutions. The chromatographic separation was applied using a mobile
phase of water and methanol (20/80), through a Nucleosil 100-
5 C18 (250 4.6 mm I.D. 5 m) column (Macherey-Nagel, Ger-
2.2. Instrument many), with an injection volume of 10 l, and a ow rate set to
1.0 mL/min. The detector responses were measured in terms of
Electrochemical measurements were carried out by using an peak area, using the Borwin chromatographic software for storage,
eDAQ e-corder/potentiostat EA163 controlled by eDAQ EChem data and data mining process.
acquisition software and equipped with three electrode system
mounted on cell. Working electrode was FAP-modied carbon 3. Results and discussion
paste electrode, the counter electrode was a platinum plate and
Ag/AgCl/Cl (3 mol/L) served as reference. The pH-meter (Ra- 3.1. Electrocatalytic behaviors of PCT at FAPCPE
diometer, sensIONTM , PH31, Spain) was used for adjusting pH
values. 3.1.1. Comparisons between CPE and FAPCPE
The electrochemical impedance measurements were done via The electrochemical response of 1.0 104 mol/L PCT in
an electrochemical impedance analyzer potentiostat (model PGZ 0.1 mol/L phosphate buffer (pH 7) at the working electrodes have
100, Eco Chemie B.V., Utrecht, The Netherlands) using a computer been studied by using cyclic voltammetry (Fig. 1A). On the unmod-
controlled by voltalab master 4 software logiciel. ied CPE (Fig. 1Aa), PCT shows a quasi-reversible redox. In the case
Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342 35

Fig. 2. CVs of 1.0 104 mol/L PCT on FAPCPE at different scan rates (1, 5, 10, 50, 100, 160, 200, 250 and 320 mV/s) in 0.1 mol/L PBS (pH 7.0). Inset, the plot of the peak
current vs. scan rate.

of FAPCPE, a pair of well-dened and reversible redox peaks cor- atively shifted. This can be due to changes in the electroactivity
responding to the electrochemical reaction of PCT was obtained, and kinetic effect of FAPCPE surface on the reduction of PCT
with Epa = 446 mV and Epc = 330 mV. It can be seen that the re- especially at scan rates lower than 5 mV/s. In other words, at scan
duction over potential of PCT becomes higher than that on CPE rates lower than 5 mV/s the time window for the PCT oxidation
with a positive shifting of 314 mV. An Epa shifted toward nega- becomes very narrow, avoiding the facile electron transfer between
tive potentials in the presence of the uoroapatite (Fig. 1Bb) was substrate and catalytic sites.
shown. The results demonstrated that the electrochemical reactiv- At high scan rates ranging from 1 to 320 mV/s, plotting the
ity of PCT is remarkably improved on the FAPCPE. Owing to its Epa and Epc vs. lnv produces a straight line with the linear re-
high adsorptivity and good biocompatibility, FAP particles effec- gression equations as: Epa = 0.032 ln(v) + 0.276 (R = 0.958) and
tively modify the surface chemistry of carbon, which provides an Epc = 0.027ln(v) + 0.475 (R = 0.996), respectively. According to
ecient interface and microenvironment for the electrochemical Lavirons equation [31], the slops of the lines are equal to RT/ nF
reaction of PCT. and RT/ nF, respectively. Therefore, the electron transfer coe-
Results conrm that the FAP can catalyze paracetamol oxida- cient ( ) and the electron transfer number (n) are calculated to be
tion, this was possible thanks to their structure, the presence of 0.54 and 2, respectively. The adsorbed amount of PCT on the sur-
Brnsted acid sites and Lewis and their ability to make exchanges face of FAPCPE was further calculated by the following equation:
ion. In the square wave voltammetric, the oxidation peak currents ip = n2 F2 A v/4RT [31]. Based on the relationship of ip with v, the
of paracetamol on the FAPCPE were about 80 fold higher than value of the surface concentration of the PCT () was obtained with
that of the unmodied electrodes (Fig. 1B). the results as 4.54 108 mol/cm2 . This high surface concentration
can be attributed to the FAP modier.
3.1.2. Effect of scan rate
The scan rate effect on the anodic and cathodic peak current 3.1.3. Effect of pH
of PCT on the FAPCPE was investigated. As shown in Fig. 2, the Fig. 3 represents CVs of the modied electrode in
anodic and cathodic peak currents increase as the scan rate grows 1.0 104 mol/L PCT at various pH values. A decrease in pH
from 5 to 250 mV/s. The linear relationship between the peak cur- of the solution from 12.0 to 2.0 led to a positive shift in both
rent and square root of scan rate can be expressed by the linear reduction and oxidation peak potentials. So the peak potentials
regression equations as: Ipa/A = 8.16(v)1/2 12.62 (R = 0.982) and seem to be affected by the concentration of H+ , suggesting the
Ipc/A = 2.39(v)1/2 4.30 (R = 0.988), respectively. According to presence of protonation step in the electrochemical mechanism
the literature, the results indicate that the electrochemical reaction as indicated in Schema 1. However, there was no considerable
of PCT on the FAPCPE is a surface-controlled process [29,30]. In decrease in the peak currents. These results indicated that the
addition, Epc is shifted to positive potentials, while Epa is neg- slope was 45.0 0.65 mV/pH over a pH range of 2.0 to 12.0. This
36 Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342

Fig. 3. CVs of FAPCPE at different pH values: 2.012.0; 1.0 104 mol/L in 0.1 mol/L PBS; Plot of Epc vs. pH value.

O O used to evaluate the electrocatalytic effect of the uoroapatite.


Fig. 4 represents the current-time proles obtained by setting the
HN C CH3 N C CH3 working electrode potential. As seen, the behavior is typical of that
expected for a mediated reduction. We found that cathodic cur-
rent of the PCT on FAPCPE is still higher than that measured on
- 2H+ the unmodied carbon paste electrode, indicating that electrode
FAPCPE has high catalytic ability to reduce PCT. This conrms
- 2e-
the results previously obtained by cyclic voltammetry. The perfor-
mance of PCT reduction on the FAPCPE reached 50% compared to
CPE. The results obtained by chronoamperometry, show that elec-
O
OH trode FAPCPE can effectively catalyze the reduction of PCT.

Schema 1. Proposed mechanism of PCT reduction. 3.3. Electrochemical impedance spectroscopy studies

Fig. 5 shows Nyquist plots of 1.0 104 mol/L in the 0.1 mol/L
value was smaller than the ideal Nernsts value of 59.2 mV/pH for
PBS at these electrodes within the frequency range of 100 kHz to
a two electron and two proton process [32]. According to the lit-
100 mHz at the formal potential of the redox probe. The almost
erature, we can predict that the mechanism depicted in Schema 1,
straight line plots obtained implies the low charge transfer resis-
seemed to be proposed for the reduction of PCT [3336]. This
tance of the redox probe [39,40]. At high frequencies, CPE (curve a)
behavior is due to the contribution of H+ ions and the structural
experiences a sharp increase of Zim and behaves closer to an ideal
changes in OH and NHCOCH3 groups of PCT which get in-
capacitor [41]. The presence of a small and depressed semicircle in
volved in the reduction process of paracetamol [37,38]. Therefore,
curve (b) at lower frequencies could be due to the charge-transfer
pH 7.0 was selected as the optimum pH for the electrochem-
resistance (Rct) of the electrodes. The FAPCPE has a higher Rct
ical determination of PCT, which is close to the physiological
which implies that the interfacial resistance has increased. This re-
conditions.
sult explains the xation of the paracetamol onto electrode surface.

3.2. Chronoamperometry studies of PCT at FAPCPE 3.4. Electroanalytical studies of PCT at FAPCPE

To conrm the results obtained by cyclic voltammetry, the In order to quantify PCT, experimental conditions has been op-
chronoamperometry as another electrochemical technique was timized using the relationships between peak current (IP) and the
Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342 37

Fig. 4. Chronoamperograms obtained of PCT at different reduction potential, 1.0 104 mol/L in 0.1 mol/L PBS.

the redox process involves the adsorption as the rate-determining


step [42]. This behavior is typical of the responses obtained at
electrodes, where the electroactive species interact with working
electrode, in the adsorption process, before the redox reaction oc-
curs. The results conrm those obtained by varying the scan rate
in cyclic volammetry.
We have also investigated the amplitude inuence in the range
from 1 to 15 mV. The results obtained demonstrated that a height
of PCT peak increased linearly as a consequence of the increase
in amplitude values up to 5 mV. In agreement with the high peak
current values, good shapes of the signal and better signal to noise
ratio were obtained, the selected optimal values were 30 Hz, 40 mV
and 5 mV for frequency, modulation amplitude and pulse height
respectively.
The effect of pH on the determination of PCT in PBS solution
at the FAPCPE was carefully investigated in the pH range of 3.0
8.0. The anodic peak current of PCT increases with increasing pH
values until the pH reaches 6.87.0, the anodic peak current then
Fig. 5. Impedance spectra at 0 V (a) CPEPCT and (b) FAPCPEPCT.
decreases with further increases in the pH. The maximum anodic
peak current appeared at pH 7.0. Therefore, PBS with a pH of 7.0
was selected for all subsequent electrochemical PCT analyses.
chemical and electrochemical parameters. All these parameters ex- Accumulation time is an important parameter for SWV tech-
ert an intense effect on the peak current. An increasing of the nique and has a non-negligible inuence on the sensitivity of de-
pulse height from 10 to 70 mV led to the increase of peak currents termination of PCT (Fig. 6). It is clear that the anodic peak intensity
of PCT. However, after 40 mV, it caused peak broadening. Therefore, increased with the increase of the preconcentration times in the
a value of 40 mV was chosen as optimal pulse height for further range from 10 s to 600 s, the anodic peak current decreased signif-
studies. icantly around 210 s after saturation of electrode surfaces. Taking
The inuence on the frequency of the current intensity of PCT account of sensitivity and eciency, accumulation time was 210 s
was evaluated in the range of 5 to 40 Hz (Fig. 6). The signal in- in the following experiments.
creases with the increase of the frequency. Thus, in further ex- The square wave voltammograms (Fig. 6) demonstrated that the
periments a value of 30 Hz, corresponds to 0.033 s of duration for increase of the concentration of uoroapatite as modier (from 10
each step, was employed to ensure the maximum diffusion of the to 80% by weight of carbon paste), affects the electrochemical be-
electro-active species to electrode surfaces. We can assume that haviors of PCT at the carbon paste electrode. The peak currents
38 Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342

Fig. 6. Inuence of the experimental variables (pulse height, amplitude, frequency, pH, time preconcentration and Percentage FAP/CP) involved in the SWV method and
response to PCT 1.0 104 mol/L in 0.1 mol/L PBS at the FAPCPE.

of PCT increase with the increase of the modier amount. More- The FAPCPE electrode here could maintain its activity as a
over, the intensity of peak decreases if the concentration of modi- sensor for parectamol during 4 months; the response was 97.15%
er is higher than 60% of FAP loading by weight (w/w). This result of its initial value which shows long-term stability and very good
is probably due to the decrease in the modied electrode conduc- sensitivity for the analysis of paracetamol.
tivity. In the course of the study, a modier concentration of about
60% of the ratio FAP/CP is used. 3.6. Effect of interferents

In order to evaluate the selectivity of the prepared sensor, the


effect of various possible interferents on the determination of PCT
3.5. Linear range and detection limit was examined, and the results were summarized in Table 2. It
was observed that Na+ , Mg2+ , Ca2+ , Cu2+ , Pb2+ , Cd2+ , K+ , Ni2+ ,
The calibration curve for the SWV peak current for PCT Co3+ , Zn2+ , Al3+ , Fe3+ , Fe2+ , V5+ , Cr3+ , NO3 , showed no ob-
oxidation vs. PCT concentration shows excellent linearity over vious interference for the determination of 1.0 105 mol/L PCT
a wide concentration range from 1.0 103 to 4.0 108 mol/L even when present 100 times in excess, with deviations below 4%.
(Fig. 7). It can be seen that the calibration plots of peak cur- However, Ag+ was found to affect the detection of PCT. It was
rent vs. concentration of PCT show two linear dynamic ranges found that 100-fold of Ag+ interfered with the determination of
from 1.0 103 4.0 105 mol/L and 2.0 105 4.0 108 mol/L 1.0 105 mol/L PCT (peak current change 5.83%). The inuences
(Fig. 7). The linear regression equations for these two re- of the presence of organic elements on the PCT signals were also
gions are ipa(A) = 0.037 [PCT] (mol/L) + 124.1 (R = 0.977) and tested. At the same concentration, ascorbic acid, citric acid, ibupro-
ipa(A)=3.238[PCT] (mol/L) + 25.73 (R = 0.990). fen and dopamine had no apparent effects on the current response
The standard deviation of the mean current (sb) measured at of PCT (2%). Electrochemically active ascorbic acid (vitamin C) is
the oxidation potential of paracetamol for 10 voltammograms of often combined with PCT based drugs. No signicant interference
the blank solution in pure electrolytes was used [43] in the deter- effect was observed in the developed SWV method up to 10 fold
mination of the quantication limit (LOQ, 10 s) and the detection concentration of ascorbic acid (Ep 200 mV) in comparison with
limit (LOD, 3 s) together with the slope of the straight line of the concentration of PCT (Ep +400 mV). As in the case of ascorbic
analytical curves. The limit of detection (DL) and limit of quanti- acid, no signicant interference effect of dopamine (Ep +200 mV)
cation (QL) are calculated to be respectively 1.25 108 mol/L and was observed under the same conditions. Both these results in-
4.16 108 mol/L. The precision (n = 8) assessed as relative stan- dicate the possibility of eventual determination of PCT simultane-
dard deviation (R.S.D.) were 1.24% for 1.0 106 mol/L and 1.07% ously with ascorbic acid or dopamine.
for 4.0 106 mol/L, respectively. The electrochemical behavior of
FAPCPE for PCT was contrasted with some of the previously re- 3.7. Practical application
ported electrodes (Table 1). It is obvious that PCT at FAPCPE
showed a low relative standard deviation, broad linearity range, In order to evaluate the performance of FAPCPE by practical
and a low detection limit. analytical applications, the determination of PCT was carried out in
Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342 39

Fig. 7. SWV curves of different concentrations of PCT in 0.1 mol/L PBS (pH 7) at FAPCPE: 1.0 103 4.0 105 mol/L and 2.0 105 4.0 108 mol/L.

Table 1
Comparison of the electrochemical behavior of PCT at FAPCPE with some of the previously
reported electrodes.

Methods Linear range (mol/L) DL (mol/L) DSR (%) Refs

6
Cu-PTTCA/GCE 2050 0 0 5.0 10 [44]
VCPTE 0.1205800 88.0 106 [45]
Naon/GCE 50500 17.0 106 [46]
GCE 21580 19.0 106 [47]
CILE 1.020 0 0 0.3 106 [48]
C60/GCE 501500 0.5 104 [49]
PANI-MWCNTs/GCE 1100 2.5 107 3.9 [50]
CNi/GCE 2230 6.0 107 1.1 [51]
PAY/nano-TiO2 /GCE 12120 2.0 106 [52]
FAP-CPE 10 0 04.0 0 and 2000.04 1.25 108 1.07 Present work

Cu-PTTCA/GCE: Cu-poly terthiophene carboxylic acid modied glassy carbon electrode.


VCPTE: Vaseline carbon paste tissue electrode.
Naon/GCE: Naon modied glassy carbon electrode.
GCE: Glassy carbon electrode.
CILE: carbon ionic liquid electrode.
PAYnano-TiO2 /GCE: poly(acid yellow 9)/nano-TiO2 modied glassy carbon electrode.
C60/GCE: C60-modied glassy carbon electrode.
PANI-MWCNTs/GCE: A polyanilinemulti-walled carbon nanotubes (PANIMWCNTs) composite
modied electrode.
CNi/GCE: A novel type of carbon-coated nickel magnetic nanoparticles modied glass carbon
electrodes.
40 Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342

Table 2
Inuence of coexisting substances on the determination of 1.0 104 mol/L PCT (n = 3).

Coexisting substance Concentration (mmol/L) Change of peak current (%) Coexisting substance Concentration (mmol/L) Change of peak current (%)

+ 3+
Na 1 1.27 Al 1 0.45
Mg2+ 1 1.65 Fe3+ 1 0.56
Ca2+ 1 1.89 Fe2+ 1 0.67
Cu2+ 1 1.20 V5+ 1 1.52
Pb2+ 1 1.48 Cr3+ 1 0.22
Cd2+ 1 1.47 NO3 1 1.27
K+1 1 0.85 Ibuprofen 0.1 0.40
Ni2+ 1 0.55 Ascorbic acid 0.1 1.72
CO2+ 1 0.28 Citric acid 0.1 1.5
Zn2+ 1 1.42 Dopamine 0.1 1.06
Ag+ 1 5.83

Fig. 8. Curves calibration of the determination of PCT in: (a) seawater (b) river water.

Table 3
Determination of PCT in water samples and human urines.

(FAP-CPE) (HPLC)
5 5
Samples PCT Added (10 mol/L) PCT found (10 mol/L) Recovery (%) PCT found (105 mol/L) Recovery (%)

River water 2 1.94 97.00 9.45 1.96 98.00


River water 4 3.96 99.00 5.74 3.99 99.75
Sea water 2 1.92 96.00 11.31 1.98 99.00
Sea water 4 3.95 98.75 6.41 3.97 99.25
Human urines 2 1.90 95.00 12.58 1.95 97.50
Human urines 4 3.92 98.00 8.08 3.94 98.50
Human urines 6 5.91 98.50 7.01 5.99 99.83

All samples were analyzed using standard addition method (n = 3).




Extended DPV-recovery (R) = (R0 (1 R0 )/n (n = 3), where R0 is the percentage recovery, t is a distribution value chosen for the desired
condence level. Theoretical values at 95% condence limits: t = 2.78.

real samples (river water, seawater, commercial tablets and human interference of the matrix components was observed even without
urines). any sample pretreatment. No signal for PCT was observed when
the water samples were analyzed, which may be attributed to that
(i) River water and seawater
no PCT is in water samples or the concentration of PCT is lower
The experiments were carried out by adding a known amount than the detection limit.
of PCT to the support electrolyte followed by standard additions
(ii) Determination of PCT in urine samples
from the PCT stock solution and plotting the resulting analyti-
cal curve. The support electrolytes were prepared by addition of FAPCPE is investigated for the measurement of PCT in three
0.1 mol/L of PBS to a fresh water samples. The plot of peak currents human urine samples. The percentage of recovery of the spiked
against PCT concentration was linear (Fig. 8). The results of the de- sample is in the range between 98.00 and 98.50. The results ob-
termination of PCT using calibration curves are given in Table 3. No tained by this method agreed with those by the HPLC. The result
Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342 41

Table 4
Determination results of PCT in tablets by FAPCPE (n = 5).

(FAPCPE) (HPLC)

Sample Label (mg/tablet) PCT found (mg/tablet) RSD (%) Recovery (%) PCT found (mg/tablet) Recovery (%)

Doliprane 10 0 0 980 1.85 98.00 985 98.50


Panadol 500 489 1.74 97.80 491 98.20

in Table 3 was mean value of replicating measurement of three [6] Abdelaleem EA, Abdelwahab NS. Validated stability indicating RP-HPLC
times. Model human urine samples were used to demonstrate that method for determination of PCT, methocarbamol and their related substances.
Anal Methods 2013;5:5415.
matrix components do not interfere with PCT determination. The [7] Wilson JM, Slattery JT, Forte AJ, Nelson SD. Analysis of acetaminophen metabo-
results show that the modied electrode is suitable for the deter- lites in urine by high performance liquid chromatography with UV and amper-
mination of PCT in biological uids ometric detection. J Chromatogr B Biomed Sci Appl 1982;227:45362.
[8] Ravisankar S, Vasudevan M, Gandhimathi M, Suresh B. Reversed-phase HPLC
method for the estimation of acetaminophen, ibuprofen and chlorzoxazone in
(iii) Determination of PCT in formulation tablets formulations. Talanta 1998;46:157781.
[9] Modick H, Schtze A, Plmke C, Weiss T, Brning T, Koch HM. Rapid deter-
The developed method was applied to the analysis of two dif- mination of N-acetyl-4-aminophenol (paracetamol) in urine by tandem mass
ferent commercial tablets. The tablets were weighed, ground into spectrometry coupled with on-line clean-up by two dimensional turbulent
powder, and then dissolved in 0.1 PBS mol/L adequately. All the ow/reversed phase liquid chromatography. J Chromatogr B Analyt Technol
Biomed Life Sci 2013;925:339.
sample solutions were transferred to 25 mL ask and diluted with [10] Roy J, Saha P, Sultana S, Kenyon AS. Rapid screening of marketed paracetamol
PBS (pH 7.0). The mean percentage recoveries of added PCT were tablets: use of thin-layer chromatography and a semi quantitative spot test.
found to be 97.80% and 98.00% using the proposed method and Bull World Health Organ 1997;75:1922.
[11] Abirami G, Vetrichelvan T. simultaneous determination of tolperisone and
HPLC, respectively (Table 4). There were no signicant differences paracetamol in pure an xed dose combination by UV-Spectrophotometry. Int
between the recoveries calculated at the 95 % condence level and J Pharm Pharm Sci 2013;5:48892.
within an acceptable range error of 5%. The excellent average re- [12] Canada MJA, Reguera MIP, Medina AR, De Cordova MLF, Diaz AM. Fast determi-
nation of paracetamol by using a very simple photometric ow-through sens-
coveries of formulation tablets samples suggest that the FAPCPE ing device. J Pharm Biomed Anal 20 0 0;22:5966.
developed in this work has practical signicance and is able to de- [13] Srivastava MK, Ahmed S, Singh D, Shukla IC. Titrimetric determination of
termine PCT in formulation tablets. dipyrone and paracetamol with potassium hexacyanoferrate (III) in an acidic
medium. Analyst 1985;110:7357.
[14] Vilchez JL, Blanc R, Avidad R, Navalon A. Spectrouorimetric determination of
4. Conclusion paracetamol in pharmaceuticals and biological uids. J Pharm Biomed Anal
1995;13:111925.
[15] Knochen M, Giglio J, Reis BF. Flow-injection spectrophotometric determi-
A highly advanced and sensitive FAPCPE toward PCT reduc- nation of paracetamol in tablets and oral solutions. J Pharm Biomed Anal
tion has been disclosed. The performances of FAPCPE were sig- 2003;33:1917.
[16] Ramos ML, Tyson JF, Curran DJ. Determination of acetaminophen by ow in-
nicantly better than those of CPE because it exhibited a re- jection with on-line chemical derivatization: investigations using visible and
markably enhanced electrocatalytical activity toward the sensing FTIR spectrophotometry. Anal Chim Acta 1998;364:10716.
of PCT. The inuence of the experimental variables which involved [17] Khanmohammadi M, Soleimani M, Morovvata F, Garmarudi AB, Khalaf-
beigi M, Ghasemi K. Simultaneous determination of paracetamol and
in the SWV determination of PCT was investigated. Analytical re-
codeine phosphate in tablets by TGA and chemometrics. Thermochim Acta
sults show that the proposed modied electrode was able to de- 2012;530:12832.
tect 1.25 108 mol/L of PCT with good sensitivity and repeatabil- [18] Pedrosa VA, Lowinsohn D, Bertotti M. FIA determination of paracetamol in
pharmaceutical drugs by using gold electrodes modied with a 3-mercapto-
ity. Results of voltammetric determination of PCT in real samples
propionic acid monolayer. Electroanalysis 2006;18:9314.
were in good agreement with those of HPLC methods proving that [19] Radovan C, Cofan C, Cinghita D. Simultaneous determination of acetaminophen
FAPCPE offers a useful and reliable method for the quantication and ascorbic acid at an unmodied boron-doped diamond electrode by
of PCT in real samples. differential pulse voltammetry in buffered media. Electroanalysis
2008;20:134653.
[20] Li M, Jing L. Electrochemical behavior of acetaminophen and its detec-
tion on the PANIMWCNTs composite modied electrode. Electrochim Acta
Acknowledgments
2007;52:32507.
[21] Lau OW, Luk SF, Cheung YM. Simultaneous determination of ascorbic acid, caf-
The authors wish to express their appreciation to the Hassan feine and paracetamol in drug formulations by differential-pulse voltammetry
1er University. This study could not have been conducted without using a glassy carbon electrode. Analyst 1989;114:104751.
[22] Xu ZM, Yue Q, Zhuang ZJ, Xiao D. Flow injection amperometric determination
their nancial supports. of acetaminophen at a gold nanoparticle modied carbon paste electrode. Mi-
crochim Acta 2009;164:38793.
[23] Teixeira MFS, Marcolino LH, Fatibello O, Moraes FC, Nunes RS. Determination
References
of analgesics (dipyrone and acetaminophen) in pharmaceutical preparations by
cyclic voltammetry at a copper(II) hexacyanoferrate(III) modied carbon paste
[1] Sun D, Zhang H. Electrochemical determination of acetaminophen using a electrode. Curr Anal Chem 2009;5:30310.
glassy carbon electrode coated with a single-wall carbon nanotube-dicetyl [24] Skeika T, De Faria MF, Nagata N, Pessoa CA. Simultaneous voltammetric deter-
phosphate lm. Microchim Acta 2007;158:1316. mination of dypirone and paracetamol with carbon paste electrode and multi-
[2] Yin H, Shang K, Meng X, Ai S. Voltammetric sensing of paracetamol, variate calibration methodology. J Braz Chem Soc 2008;19:7628.
dopamine and 4-aminophenol at a glassy carbon electrode coated with gold [25] Hidalgo-Carrillo J, Sebti J, Aramenda MA, Marinas A, Marinas JM, Sebti S,
nanoparticles and an organophilliclayered double hydroxide. Microchim Acta et al. A study on the potential application of natural phosphate in photocat-
2011;175:3946. alytic processes. J Colloid Interf Sci 2010;344:47581.
[3] Tsierkezos NG, Othman SH, Ritter U. Nitrogen-doped multi-walled carbon nan- [26] Sebti S, Zahouily M, Lazrek HB, Mayoral JA, Macquarrie DJ. Phosphates: new
otubes for PCT sensing. Ionics 2013;19:1897905. generation of liquid-phase heterogeneous catalysts in organic chemistry. Curr
[4] Loureno BC, Medeiros RA, Rocha-Filho RC, Mazo LH, Fatibello-Filho O. Org Chem 2008;12:20332.
Simultaneous voltammetric determination of PCT and caffeine in phar- [27] Vieillard P, Tardy Y, Nriagu JO, Moore PB. Phosphate minerals. New York:
maceutical formulations using a boron-doped diamond electrode. Talanta Springer-Verlag; 1984.
2009;78:74852. [28] El Mhammedi MA, Bakasse M, Chtaini A. Investigation of square wave
[5] Sultan MA, Maher HM, Alzoman NZ, Alshehri MM, Rizk MS, Elshahed MS, voltammetric detection of diquat at carbon paste electrode impregnated
et al. Capillary electrophoretic determination of antimigraine formulations with Ca10 (PO4 )6F2 : application in natural water samples. Mater Chem Phys
containing caffeine, ergotamine, PCT and domperidone or metoclopramide. 2008;109:51925.
Chromatogr Sci Ser 2013;51:50210.
42 Y. EL Bouabi et al. / Journal of the Taiwan Institute of Chemical Engineers 66 (2016) 3342

[29] Dalmasso PR, Pedano ML, Rivas GA. Electrochemical determination of ascorbic [40] Fan H, Li Y, Wu D, Ma H, Mao K, Fan D, et al. Electrochemical bisphenol A
acid and paracetamol in pharmaceutical formulations using a glassy carbon sensor based on N-doped grapheme sheets. Anal Chim Acta 2012;711:248.
electrode modied with multi-wall carbon nanotubes dispersed in polyhisti- [41] Tehrani RMA, Ab Ghani S. MWCNT-ruthenium oxide composite paste electrode
dine. Sens Actuators: B Chem 2012;173:7326. as non-enzymatic glucose sensor. Biosens Bioelectron 2012;38:27883.
[30] Lu TL, Tsai YC. Sensitive electrochemical determination of acetaminophen [42] Lovric M, Komorsky-Lovric S. Square-wave voltammetry of an adsorbed reac-
in pharmaceutical formulations at multiwalled carbon nanotube-alumina tant. J Electroanal Chem 1988;248:23953.
coated silica nanocomposite modied electrode. Sens Actuators: B Chem [43] Mocak J, Bond AM, Mitchel S, Scollary GA. Statistical overview of standard
2011;153:43944. (IUPAC and ACS) and new procedures for determining the limits of detection
[31] Laviron E. General expression of the linear potential sweep voltammogram and quantication: application to voltammetric and stripping techniques. Pure
in the case of diffusion less electrochemical systems. J Electroanal Chem Appl Chem 1997;69:297328.
1979;101:1928. [44] Boopathi M, Won MS, Shim YB. A sensor for acetaminophen in a blood
[32] Rahimi P, Raee-Pour H, Ghourchian H, Norouzi P, Ganjali MR. Ionic-liquid/ medium using a Cu(II)-conducting polymer complex modied electrode. Anal
NH2-MWCNTs as a highly sensitive nano-composite for catalase direct electro- Chim Acta 2004;512:1917.
chemistry. Biosens Bioelectron 2010;25:13016. [45] Fatibello-Filho O, Lupetti KO, Vieira IC. Chronamperometric determination of
[33] Ghorbani-Bidkorbeh F, Shahrokhian S, Mohammadi A, Dinarvand R. Simul- paracetamol using an avocado tissue (Persea Americana) biosensor. Talanta
taneous voltammetric determination of tramadol and acetaminophen us- 2001;55:68592.
ing carbon nanoparticles modied glassy carbon electrode. Electrochim Acta [46] Silva MLS, Garcia MBQ, Lima JLFC, Barrado E. Modied tubular electrode
2010;55:27529. in a multi-commutated ow system: determination of acetaminophen
[34] Zidan M, Tan W, Abdullah AH, Zainal Z, Goh JK. Electrocatalytic oxidation of in blood serum and pharmaceutical formulations. Anal Chim Acta
paracetamol mediated by lithium doped microparticles Bi2 O3 /MWCNT modi- 2006;573574:38390.
ed electrode. Asian J Chem 2011;23:302932. [47] Tungkananuruk K, Tungkananuruk N, Burns DT. Cyclic voltammetric deter-
[35] Li C, Zhan G, Yang Q, Lu J. Electrochemical Investigation of acetaminophen mination of acetaminophen in paracetamol tablets. KMITL Sci Technol J
with a carbon nano-tube composite lm electrode. Bull Korean Chem Soc 2005;5:54751.
2006;27:185460. [48] ShangGuan X, Zhang H, Zheng J. Electrochemical behavior and differential
[36] Sotomayor M, Sigoli A, Lanza MRV, Tanaka AA, Kubota LT. Construction and pulse voltammetric determination of paracetamol at a carbon ionic liquid elec-
application of an electrochemical sensor for paracetamol determination based trode. J Anal Chem 2008;391:104955.
on iron tetrapyridinoporphyrazine as a biomimetic catalyst of P450 enzyme. J [49] Goyal RN, Singh SP. Voltammetric determination of paracetamol at
Braz Chem Soc 2008;19:73443. C60-modied glassy carbon electrode. Electrochim Acta 20 06;51:30 0812.
[37] Su WY, Cheng SH. Electrochemical oxidation and sensitive determination [50] Mingqi L, Linhai J. Electrochemical behavior of acetaminophen and its detec-
of acetaminophen in pharmaceuticals at poly(3,4-ethylenedioxythiophene)- tion on the PANIMWCNTs composite modied electrode. Electrochim Acta
modied screen-printed electrodes. Electroanalysis 2010;22:70714. 2007;52:32507.
[38] Manjunatha R, Nagaraju DH, Suresh GS, Melo JS, DSouza SF, Venkate- [51] Wang SF, Xie F, Hu RF. Carbon-coated nickel magnetic nanoparticles modied
sha TV. Electrochemical detection of acetaminophen on the functionalized electrodes as a sensor for determination of acetaminophen. Sens Actuators: B
MWCNTs modied electrode using layer-by-layer technique. Electrochim Acta Chem 2007;123:495500.
2011;56:661927. [52] Kumar SA, Tang CF, Chen SM. Electroanalytical determination of ac-
[39] Luo J, Jiang S, Zhang H, Jiang J, Liu X. A novel non-enzymatic glucose sensor etaminophen using nano-TiO2 /polymer coated electrode in the presence of
based on Cu nanoparticle modied graphene sheets electrode. Anal Chim Acta dopamine. Talanta 20 08;76:99710 05.
2012;709:4753.