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A new simple electrochemical Moxifloxacin Hydrochloride sensor built on carbon paste modified with silver nanoparticles
Author’s Accepted Manuscript A new simple electrochemical Moxifloxacin Hydrochloride sensor built on carbon paste modified with silver nanoparticles A.M. Fekry www.elsevier.com/locate/bios
PII: DOI: Reference:
S0956-5663(16)30707-2 http://dx.doi.org/10.1016/j.bios.2016.07.077 BIOS8958
To appear in: Biosensors and Bioelectronic Received date: 15 June 2016 Accepted date: 22 July 2016 Cite this article as: A.M. Fekry, A new simple electrochemical Moxifloxacin Hydrochloride sensor built on carbon paste modified with silver nanoparticles, Biosensors and Bioelectronic, http://dx.doi.org/10.1016/j.bios.2016.07.077 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A new simple electrochemical Moxifloxacin Hydrochloride sensor built on carbon paste modified with silver nanoparticles A. M. Fekry* Chemistry Department, Faculty of Science, Cairo University, Giza-12613, Egypt.
*Corresponding author: Tel: 202 0101545331. E-mail: [email protected]
Abstract A new sensitive simple electrochemical sensor for Moxifloxacin Hydrochloride (MOXI) detection has been successfully performed. The sensor built on carbon paste (CP) modified with silver nanoparticles (AgNPs). AgNPs are biocompatible stable noble materials especially in biological sensing. The silver nanoparticles modified carbon paste electrode (SNMCPE) displayed high electrocatalytic activity towards oxidation of 1.0 mM MOXI in Britton Robinson (BR) buffer of pH range (2.0–9.0). The techniques used to do this work are cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS). Surface characteristics were achieved using scanning electron microscopic (SEM) and Energy Dispersive X-Ray Analysis (EDX) techniques. The effect of changing MOXI concentration (7.0×10-7 to 1.8×10-4 M) was studied in BR buffer (pH = 7.4) at a scan rate of 50 mV/s using SNMCPE. The detection and quantification limits were found to be 2.9×10-9 M and 9.6 x 10-8 M, respectively. In order to assess the applicability of MOXI detection method in real samples; this method was tested in Delmoxa tablet and human urine sample. Good sensible results were attained for MOXI detection. Keywords: Moxifloxacin Hydrochloride; Ag Nanoparticles; EIS; SEM; EDX.
1. Introduction Nanoparticle investigation field becomes significant owing to its sole chemical and physical possessions. Silver nanoparticles (AgNPs) have low cost value and environmentally friendly (Kohsaria et al., 2016), so, they were widely applied in medical field particularly biodegradable surgical sutures manufacture. Ag is a noble metal, so, AgNPs with their biocompatibility, stability, optical properties, excellent catalytic activity, low toxicity, high conductivity and antibacterial activity can be used for excellent estimates in biological sensing, imaging and medical applications (Raghavendra et al., 2016; Baghayeri et al., 2016). Recently, many electrochemical sensors built on silver nanoparticles were used as AgNPs decorated silicon nanowire arrays (Yin et al., 2011) and/or carbon quantum dots supported with silver nanoparticles (Jahanbakhshi and Habibi, 2016) were used for H2O2 determination. U-shaped fiber-optic ATR sensor enhanced by AgNPs is used for glucose determination (Li et al., 2015). AgNPs-Tagged carbon nanospheres have been used as a competitive method joined with Endonuclease-Assisted target recycling for DNA detection (Zhu et al., 2012). A highly sensitive method combined circular strand-displacement polymerization with silver for target DNA detection reached double signal magnification (Gao et al., 2013). Moxifloxacin Hydrochloride (1-cyclopropyl-6-fluoro-1,4- dihydro- 8-methoxy-7-[(4aS,7aS)octahydro-6H-pyrrolo [3,4-b]pyridin-6-yl]4-oxo-3 quinoline carboxylic acid) (Fig.1C as inset) is an antimicrobial fluoroquinolones with an effective antimicrobial activity and respectable clinical effects with slight toxicity (Zhou et al., 2015). It appears at 1999 (Hefnawy et al., 2014). Fluoroquinolones are antibiotics active against bacteria, both gram-positive and gram-negative types (Kaur et al., 2008). Its Tablets are principally applied in bacterial sinusitis treatment. The
World Health Organization intensely recommend MOXI in medicine usage (Kim and Aga, 2007; Kummerer, 2003). Quinolones are used in urinary tract infections remedy (Kuester et al., 2013). Pharmaceutical molecules detection needs complicated expensive methods as GC–MS examination (Reinemann et al., 2016). Several other methods were used in literature to determine it, as spectrophotometry, spectrofluorimetry, high performance liquid chromatography ultraviolet, capillary electrophoresis and others. However, all of them need timewasting dealings and/or sophisticated devices. Recently, MOXI is of excessive pharmacological significance and a scarce electrochemical work was done on it in literature. MOXI determination with innovative fast and easy methods is desired than classical chemical methods. The aim of this work is to synthesize a simple, easy and cheap silver nanoparticles modified carbon paste electrode (SNMCPE) as an innovative sensitive and selective sensor for MOXI. The electrochemical behavior of the sensor was studied using cyclic, linear sweep voltammetry and impedance measurements. SEM and EDX analysis is done to understand the surface morphology. The selectivity and sensitivity of the sensor were accomplished in real samples. 2. Experimental 2.1. Materials and reagents The Chemicals used in the present work are Moxifloxacin Hydrochloride, Delmoxa tablet (from delta pharma), graphite and silver nanoparticles powder, dispersion nanoparticles, <100 nm (Sigma Aldrich). Britton Robinson (BR) (CH3COOH + H3BO3 + H3PO4) (4.0 × 10−2 M) buffer solution (pH 2.0–9.0) (Fekry et al., 2015; Shehata et al., 2016) is used for making Moxifloxacin Hydrochloride standard solutions and pH values adjusted by 0.2 M NaOH. All solutions are prepared using Triple distilled water. All experiments were performed at room temperature.
2.2. SNMCPE preparation CPE is prepared by blending well 0.5 g graphite powder with paraffin oil drops using a morter and then 5 mg of silver nanoparticles are added to prepare the sensor (SNMCPE) by filling a Teflon tube with the paste and pressing it well to obtain smooth surface. 2.3. Cell and Apparatus A three-electrode cell, containing a platinum rod as a counter electrode (CE), saturated calomel electrode (SCE) as a reference electrode (RE) and SNMCPE as the working electrode (WE), is used. Cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CA) and Electrochemical impedance spectroscopic (EIS) measurements are performed by SP150 potentiostat supplied with EC-Lab® software package. EIS measurements are done using 10 mV ac amplitude in the frequency range of 1.0 mHz to 100 kHz. EC-Lab® software is used to analyse and fit the experimental spectra using the best equivalent circuit model. A microprocessor digital pH-meter (Hanna instruments, Italy) is used for pH measurements. Scanning electron microscopic (SEM) measurements are done by SEM Model Quanta 250 FEG (Field Emission Gun) connected to EDX Unit (Energy Dispersive X-ray Analyses) (FEI company, Netherlands) .
3. RESULTS AND DISCUSSION 3.1. Characterization of the modified electrode
Figure.1. SEM of AgNPs modified carbon paste electrode (A). EDX spectra of AgNPs (B). CVs of MOXI at Bare CPE and SNMCPE using BR buffer (pH 7.4), at a scan rate 50 mV/s (C). Inset: Schematic of the interaction between MOXI and AgNPs.
Figure 1A shows the SEM image of the silver nanoparticles modified carbon paste electrode (SNMCPE). Generally, the size of silver nanoparticles is among 1 to 100 nm (Graf et al., 2003) and from SEM image (Fig. 1A); it is in the range from 10 to 90 nm. The surface appears to be quasi-spherical, finely dispersed and vertically oriented (Sistani et al., 2014), displaying a larger surface area. EDX analysis (Figure 1B) shows Ag peaks confirming the existence of AgNPs on the CPE surface. 3.2. Electrochemistry of Moxifloxacin Hydrochloride The interaction of 1.0 mM MOXI with AgNPs was studied using CV technique. Figure 1C shows the two CVs of the bare CPE and SNMCPE in BR buffer solution (pH = 7.4) at a scan rate 50 mV/S. The oxidation of MOXI at SNMCPE presented a well-defined irreversible oxidation peak at +940 mV with a peak current about ~ 1.6 times higher than that of the bare CPE. This reveals that MOXI molecule adsorbed on the modified electrode surface through silver nanoparticles where the oxidation takes place at the piperazine moiety (Zhou et al., 2015, Radi and El-Sharif, 2002; Girousi et al. 2004), indicating the occurrence of the MOXI-Ag(I) complex via an electrostatic interaction between the cationic MOXI and the anionic nano-silver (Schematic inset Fig.1C). MOXI contains active functional groups like hydroxyl and amide groups which can bind easily with nano-silver by chelation and form nano-silver core complex (Sripriya et al., 2013). This formed complex reflects MOXI binding with surface-containing nano-silver that greatly enhances the sensitivity performance of the tested electrode (Zhou et al., 2015). On the reverse scan, no reduction peak is observed, confirming that the electrode process of MOXI is totally irreversible.
3.3. Optimization of detection test conditions 3.3.1. Effect of pH
Figure 2: CVs of MOXI in different pH values using SNMCPE, at a scan rate 50 mV/s. Inset: A) Variation of anodic peak current with pH, at bare CPE and SNMCPE. B) Variation of anodic peak potential with pH, at SNMCPE.
Cyclic
voltammetry
(CV)
technique
was
processed
to
study
the
effect of solution pH on the electrocatalytic oxidation of 1.0 mM MOXI in BR buffer (pH 2.0-9.0) at bare CPE and SNMCPE, respectively (Figure 2). The effect of pH on the peak current and the peak potential for the oxidation of MOXI is obviously seen in Figure 2 as insets. The anodic peak potentials shifted negatively and broadened as the pH increases, revealing that the electrocatalytic oxidation of MOXI was a pH-dependent reaction with participation of protons
(Ocana
et
al.,
2000)
and
that
the
proton-transfer
reaction
precedes
the electron transfer (Zuman, 1969), i.e. two electrons transferred per molecule (Berg et al., 1981).
As
can
be
seen,
the
peak
current
of
the
formed
complex
increases
on going from pH 2.0 to 6.0. At pH 7.4, the peak current is maximized and then at higher pH values the current decreases abruptly. This approves the predictable performance of protondependent method with irreversible chemical reaction (Zhang and Wei, 2007). As MOXI has a pKa value of 6.25 and 9.29 (Langlois et al., 2005), thus, the chosen pH value of 7.4 adequately brackets the area near the first dissociation of MOXI. 3.3.2. Effect of scan rate and electroactive area calculation A study for a scan rate effect on the anodic peak current of 1.0 mM MOXI has been done by cyclic voltammetry method [See Supplementary material (Figure 1)]. The relation between anodic peak current and the scan rate (ν ranging from 10 to 300 mV/s) gives a linear relationship as shown in the inset. It can be given by the linear equation (Baghayeri et al., 2016): Ip(μA) = 0.89 ν + 34.9 (r = 0.996), which implies that the oxidation process of MOXI is adsorptioncontrolling process (Bard and Faulker, 2001). Also, it is clear that the peak potentials of MOXI are shifted to the positive direction with increasing the scan rate indicating reaction irreversibility (Zuman, 1969). The active surface area of the modified electrode was estimated for a known concentration of K4Fe(CN)6, based on the Randles–Sevcik equation (Roychoudhury et al., 2016): Ip= 2.69 x 015 n3/2 AD1/2 ν
1/2
C, Where Ip is the peak current (A), n is the number of electrons transferred, v is
the scan rate (V s-1), D the diffusion coefficient, A is the electrode area and C is the concentration of K4Fe(CN)6. For 0.0 mmol L-0 K4Fe(CN)6 in 0.10 mol L-0 KCl electrolyte with n = 1 and D = 7.6×10−6 cm s-0 . The area of the bare is 0.07 cm2 and electroactive surface area of SNMCPE was calculated to be 0.125 cm.2
3.3.3. Chronoamperometry [See Supplementary material (Figure 2)] shows the chronoamperometric measurements of MOXI, performed at a constant potential (+940 mV vs. SCE) using SNMCPE in BR buffer (pH = 7.4) containing different MOXI concentrations. Using the Cottrell equation (Bard and Faulkner, 1980), the diffusion coefficient can be calculated
nFAc 0 D i t
(1)
Where i = current, in unit A, n = number of electrons, F = Faraday constant, 96,485 C/mol, A = area of the electrode in cm2, c0 = bulk concentration of the analyte in mol/cm3; D = diffusion coefficient for species in cm2/s and t = time in s. According to the Cottrell equation, the slope obtained from the relation between anodic peak current and t-1/2 (inset) equals nFA (D/π)1/2, so the diffusion coefficient of MOXI was calculated to be 4.376 x 10-6 cm2 s-1. [See Supplementary material (Figure 2 inset)] shows the calibration curve as a linear relationship between different MOXI concentrations (10 to 70 mM) and the current at a fixed time of 2 seconds. The linear equation was Ip(µA)= 7.197C + 1.188 with a correlation coefficient of 0.973. The steady state oxidation current increases with gradual increase in MOXI concentration (Baghayeri et al., 2016). 3.3.4. Effect of repeated CVs
[See Supplementary material (Figure 3)] displays the repeated CVs of 1.0 mM MOXI in BR buffer (pH 7.4), from which, it is clear that the peak current value decreased (inset) from the first scan to the rest scans. This may be due to an adsorption for the oxidation product as an adsorbed film on SNMCPE surface that deactivates and decreases the electroactive surface area of the sensor (Chen et al., 2013). The reproducibility and precision of SNMCPE is performed by repeating the measurement five times that gives relative standard deviation (R.S.D) of 2.16% for the first anodic scan. To attain innovative sensitivity and reproducibility, a first anodic peak current must be recorded for all the analysis in the coming studies. 3.4. EIS measurements
Figure 3: Nyquist plots of MOXI in different pH values using SNMCPE at peak potential. Inset: Nyquist plots of MOXI at Bare CPE and SNMCPE using BR buffer (pH 7.4), at peak potential. Inset: Model used for fitting. Impedance plots are shown as Nyquist plots (Fig. 3 inset) for both the Bare and SNMCPE electrodes. It shows a semicircle corresponds to a charge transfer resistance and a line corresponds to a diffusion process at both high and low frequencies, respectively. The best model
that fits the experiments (Fig. 3 inset) is a one-time constant model consists of Rs (solution resistance), RCT (Charge transfer resistance), W (Warburg impedance) and CPE (constant phase element of capacitance) (Fekry, 2016). The data were simulated to this equivalent circuit model. W is due to the linear region at low frequency (diffusion process) (Fekry et al., 2015, Fekry, 2010), RCT is due to the semicircle at high frequency (charge transfer resistance). A constantphase element (CPE) (Fekry, 2016) was introduced to account for surface non-ideality and heterogeneity, its impedance is ZCPE = [C(jω)α]−1 , where α is due to the surface inhomogeneity ( −1 ≤ α ≤ 1), j is the imaginary number (j2 = -1), ω = 2πf (rad s-1) and f (Hz) is the frequency. Thus, the reaction mechanism depends on both charge transfer and diffusion process (Fekry et al., 2011). The fitting is performed using EC-Lab® software provided with SP-150 workstation. SNMCPE electrode shows higher value for the CPE (5.2 µF cm-2), Warburg impedance (812 Ω cm2 s-1/2) and lower values for the charge transfer resistance (1100 Ω cm2) indicating a higher conductivity compared to the bare electrode with CPE = 3.0 µF cm-2, W = 212 Ω cm2 s-1/2 and RCT = 5300 Ω cm2 . These results approve well the highest oxidation peak current obtained from CVs results to SNMCPE electrode. Also, Nyquist plots (Fig. 3) of MOXI in different pH values using SNMCPE at 940 mV vs. SCE (peak potential) was measured and give the same order of pH obtained from CVs results. The impedance value decreases in the same order as the current increases indicating an increase in the conductivity. This indicates that pH 7.4 is the lowest in impedance value with lower semicircle diameter compared to the bare electrode (inset) and highest conductivity as obtained from CVs results with highest current (Shehata et al., 2016). 3.5. Calibration curve and detection limit
Figure 4: Effect of successive addition of MOXI in BR buffer (pH 7.4) using SNMCPE at a scan rate 10 mV/s. Inset: Calibration curve of MOXI using SNMCPE.
Figure 4 shows CVs of the effect of changing MOXI concentration (7.0×10-7 to 1.8×10-4 M) in BR buffer (pH 7.4) at a scan rate 10 mV/s using SNMCPE. Figure 4 (inset) shows a linear relationship with a linear regression equation: Ip(µA)= 0.0694C + 1.326. The limit of detection (LOD) and limit of quantification (LOQ) were determined according to the IUPAC recommendation (Meier and Zünd , 2000; Fekry et al., 2015) and were found to be 2.9×10-9 M and 9.6 x 10-8 M, respectively. 3.6. Sample analysis
A determination of MOXI in real samples has been performed to estimate the planned method applicability. The established method was tested in Delmoxa tablet (from delta pharma) and human urine sample. Each Delmoxa tablet contains 400 mg MOXI. Five tablets were grinded and weighed to obtain 1.0 mM MOXI solution. Four drug aliquots were presented into the cell and the concentration was determined from the calibration curve. Average concentrations were calculated from five replicate measurements. [See Supplementary material (Table 1)] shows the data generated by standard addition method for the examination of MOXI in buffered solution of pH 7.4. Also, the planned method is right for the quantitative test of the MOXI in urine sample. The calibration curve in Figure 5A gave a straight line with a linear dynamic range 4 x 10-6 M – 1.6 x 10-4 M and LOD = 2.1 ×10−8 M. Four different concentrations are selected to recurring four times to estimate the accuracy and precision of the planned method which is represented in (Table 1). The outcomes displays that the excipient materials in tablets and matrices in urine have no interference in the determination.
Table 1. Evaluation of the accuracy and precision of the proposed method for the determination of (MOXI) in urine sample [MOXI] added (M) x 10-6
[MOXI] Founda
Recovery
SD
S.Eb
C.L.c
(M) x 10-6
(%)
x 10-6
x 10-6
x 10-6
a
5.00
5.22
104.4
0.73
0.41
1.04
50.0
50.09
100.1
0.51
1.31
1.55
100.0
100.6
100.6
1.63
0.77
2.18
160.0
157.05
98.15
1.93
0.98
0.12
mean for five determinations b Standard error = SD/√n c C.L. confidence at 95%confidence level and 4 degrees of freedom (t=2.776)
Figure 5: Calibration curve of MOXI in urine (A). Simultaneous determination of 2 x 10-6 M MOXI and 5 x 10-6 M ACOP (B).
3.7. Simultaneous determination of MOXI and Paracetamol Patient that had high grade fever and dry cough must take 200 mg moxifloxacin orally each 12 hour and 500 mg paracetamol (ACOP) when required (Mandavia et al., 2012). Therefore simultaneous determination of 2 x 10-6 M MOXI with 5 x 10-6 M ACOP in BR buffer (pH 7.4) using SNMCPE at a scan rate 50 mV/s was performed. Figure 5B shows a well separation between ACOP (appears at 580 mV) and MOXI (appears at 940 mV) with ΔE of 360 mV, which indicates the electrocatalytic activity of MOXI and ACOP in the existence of each other. 4. Conclusions A carbon paste sensor with an excellent performance for the electrochemical determination of MOXI built on silver nanoparticles was performed. Silver nanoparticles enhanced the sensitivity of MOXI significantly. The detection limit found to be 2.9×10-9 M. Also, excipients interference of the drugs does not interfere with MOXI. The results showed that the method was easy, cheap, simple and sensitive enough for the determination of MOXI in Delmoxa tablet and human urine under physiological conditions with good precision and low detection limit.
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Highlights
A new simple silver nanoparticle modified carbon paste electrode for MOXI sensing. It gives excellent performance with 2.9×10-9 M detection limit.
The sensor is effective for determination of MOXI in Delmoxa tablet and human urine.
PII: DOI: Reference:
S0956-5663(16)30707-2 http://dx.doi.org/10.1016/j.bios.2016.07.077 BIOS8958
To appear in: Biosensors and Bioelectronic Received date: 15 June 2016 Accepted date: 22 July 2016 Cite this article as: A.M. Fekry, A new simple electrochemical Moxifloxacin Hydrochloride sensor built on carbon paste modified with silver nanoparticles, Biosensors and Bioelectronic, http://dx.doi.org/10.1016/j.bios.2016.07.077 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A new simple electrochemical Moxifloxacin Hydrochloride sensor built on carbon paste modified with silver nanoparticles A. M. Fekry* Chemistry Department, Faculty of Science, Cairo University, Giza-12613, Egypt.
*Corresponding author: Tel: 202 0101545331. E-mail: [email protected]
Abstract A new sensitive simple electrochemical sensor for Moxifloxacin Hydrochloride (MOXI) detection has been successfully performed. The sensor built on carbon paste (CP) modified with silver nanoparticles (AgNPs). AgNPs are biocompatible stable noble materials especially in biological sensing. The silver nanoparticles modified carbon paste electrode (SNMCPE) displayed high electrocatalytic activity towards oxidation of 1.0 mM MOXI in Britton Robinson (BR) buffer of pH range (2.0–9.0). The techniques used to do this work are cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS). Surface characteristics were achieved using scanning electron microscopic (SEM) and Energy Dispersive X-Ray Analysis (EDX) techniques. The effect of changing MOXI concentration (7.0×10-7 to 1.8×10-4 M) was studied in BR buffer (pH = 7.4) at a scan rate of 50 mV/s using SNMCPE. The detection and quantification limits were found to be 2.9×10-9 M and 9.6 x 10-8 M, respectively. In order to assess the applicability of MOXI detection method in real samples; this method was tested in Delmoxa tablet and human urine sample. Good sensible results were attained for MOXI detection. Keywords: Moxifloxacin Hydrochloride; Ag Nanoparticles; EIS; SEM; EDX.
1. Introduction Nanoparticle investigation field becomes significant owing to its sole chemical and physical possessions. Silver nanoparticles (AgNPs) have low cost value and environmentally friendly (Kohsaria et al., 2016), so, they were widely applied in medical field particularly biodegradable surgical sutures manufacture. Ag is a noble metal, so, AgNPs with their biocompatibility, stability, optical properties, excellent catalytic activity, low toxicity, high conductivity and antibacterial activity can be used for excellent estimates in biological sensing, imaging and medical applications (Raghavendra et al., 2016; Baghayeri et al., 2016). Recently, many electrochemical sensors built on silver nanoparticles were used as AgNPs decorated silicon nanowire arrays (Yin et al., 2011) and/or carbon quantum dots supported with silver nanoparticles (Jahanbakhshi and Habibi, 2016) were used for H2O2 determination. U-shaped fiber-optic ATR sensor enhanced by AgNPs is used for glucose determination (Li et al., 2015). AgNPs-Tagged carbon nanospheres have been used as a competitive method joined with Endonuclease-Assisted target recycling for DNA detection (Zhu et al., 2012). A highly sensitive method combined circular strand-displacement polymerization with silver for target DNA detection reached double signal magnification (Gao et al., 2013). Moxifloxacin Hydrochloride (1-cyclopropyl-6-fluoro-1,4- dihydro- 8-methoxy-7-[(4aS,7aS)octahydro-6H-pyrrolo [3,4-b]pyridin-6-yl]4-oxo-3 quinoline carboxylic acid) (Fig.1C as inset) is an antimicrobial fluoroquinolones with an effective antimicrobial activity and respectable clinical effects with slight toxicity (Zhou et al., 2015). It appears at 1999 (Hefnawy et al., 2014). Fluoroquinolones are antibiotics active against bacteria, both gram-positive and gram-negative types (Kaur et al., 2008). Its Tablets are principally applied in bacterial sinusitis treatment. The
World Health Organization intensely recommend MOXI in medicine usage (Kim and Aga, 2007; Kummerer, 2003). Quinolones are used in urinary tract infections remedy (Kuester et al., 2013). Pharmaceutical molecules detection needs complicated expensive methods as GC–MS examination (Reinemann et al., 2016). Several other methods were used in literature to determine it, as spectrophotometry, spectrofluorimetry, high performance liquid chromatography ultraviolet, capillary electrophoresis and others. However, all of them need timewasting dealings and/or sophisticated devices. Recently, MOXI is of excessive pharmacological significance and a scarce electrochemical work was done on it in literature. MOXI determination with innovative fast and easy methods is desired than classical chemical methods. The aim of this work is to synthesize a simple, easy and cheap silver nanoparticles modified carbon paste electrode (SNMCPE) as an innovative sensitive and selective sensor for MOXI. The electrochemical behavior of the sensor was studied using cyclic, linear sweep voltammetry and impedance measurements. SEM and EDX analysis is done to understand the surface morphology. The selectivity and sensitivity of the sensor were accomplished in real samples. 2. Experimental 2.1. Materials and reagents The Chemicals used in the present work are Moxifloxacin Hydrochloride, Delmoxa tablet (from delta pharma), graphite and silver nanoparticles powder, dispersion nanoparticles, <100 nm (Sigma Aldrich). Britton Robinson (BR) (CH3COOH + H3BO3 + H3PO4) (4.0 × 10−2 M) buffer solution (pH 2.0–9.0) (Fekry et al., 2015; Shehata et al., 2016) is used for making Moxifloxacin Hydrochloride standard solutions and pH values adjusted by 0.2 M NaOH. All solutions are prepared using Triple distilled water. All experiments were performed at room temperature.
2.2. SNMCPE preparation CPE is prepared by blending well 0.5 g graphite powder with paraffin oil drops using a morter and then 5 mg of silver nanoparticles are added to prepare the sensor (SNMCPE) by filling a Teflon tube with the paste and pressing it well to obtain smooth surface. 2.3. Cell and Apparatus A three-electrode cell, containing a platinum rod as a counter electrode (CE), saturated calomel electrode (SCE) as a reference electrode (RE) and SNMCPE as the working electrode (WE), is used. Cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CA) and Electrochemical impedance spectroscopic (EIS) measurements are performed by SP150 potentiostat supplied with EC-Lab® software package. EIS measurements are done using 10 mV ac amplitude in the frequency range of 1.0 mHz to 100 kHz. EC-Lab® software is used to analyse and fit the experimental spectra using the best equivalent circuit model. A microprocessor digital pH-meter (Hanna instruments, Italy) is used for pH measurements. Scanning electron microscopic (SEM) measurements are done by SEM Model Quanta 250 FEG (Field Emission Gun) connected to EDX Unit (Energy Dispersive X-ray Analyses) (FEI company, Netherlands) .
3. RESULTS AND DISCUSSION 3.1. Characterization of the modified electrode
Figure.1. SEM of AgNPs modified carbon paste electrode (A). EDX spectra of AgNPs (B). CVs of MOXI at Bare CPE and SNMCPE using BR buffer (pH 7.4), at a scan rate 50 mV/s (C). Inset: Schematic of the interaction between MOXI and AgNPs.
Figure 1A shows the SEM image of the silver nanoparticles modified carbon paste electrode (SNMCPE). Generally, the size of silver nanoparticles is among 1 to 100 nm (Graf et al., 2003) and from SEM image (Fig. 1A); it is in the range from 10 to 90 nm. The surface appears to be quasi-spherical, finely dispersed and vertically oriented (Sistani et al., 2014), displaying a larger surface area. EDX analysis (Figure 1B) shows Ag peaks confirming the existence of AgNPs on the CPE surface. 3.2. Electrochemistry of Moxifloxacin Hydrochloride The interaction of 1.0 mM MOXI with AgNPs was studied using CV technique. Figure 1C shows the two CVs of the bare CPE and SNMCPE in BR buffer solution (pH = 7.4) at a scan rate 50 mV/S. The oxidation of MOXI at SNMCPE presented a well-defined irreversible oxidation peak at +940 mV with a peak current about ~ 1.6 times higher than that of the bare CPE. This reveals that MOXI molecule adsorbed on the modified electrode surface through silver nanoparticles where the oxidation takes place at the piperazine moiety (Zhou et al., 2015, Radi and El-Sharif, 2002; Girousi et al. 2004), indicating the occurrence of the MOXI-Ag(I) complex via an electrostatic interaction between the cationic MOXI and the anionic nano-silver (Schematic inset Fig.1C). MOXI contains active functional groups like hydroxyl and amide groups which can bind easily with nano-silver by chelation and form nano-silver core complex (Sripriya et al., 2013). This formed complex reflects MOXI binding with surface-containing nano-silver that greatly enhances the sensitivity performance of the tested electrode (Zhou et al., 2015). On the reverse scan, no reduction peak is observed, confirming that the electrode process of MOXI is totally irreversible.
3.3. Optimization of detection test conditions 3.3.1. Effect of pH
Figure 2: CVs of MOXI in different pH values using SNMCPE, at a scan rate 50 mV/s. Inset: A) Variation of anodic peak current with pH, at bare CPE and SNMCPE. B) Variation of anodic peak potential with pH, at SNMCPE.
Cyclic
voltammetry
(CV)
technique
was
processed
to
study
the
effect of solution pH on the electrocatalytic oxidation of 1.0 mM MOXI in BR buffer (pH 2.0-9.0) at bare CPE and SNMCPE, respectively (Figure 2). The effect of pH on the peak current and the peak potential for the oxidation of MOXI is obviously seen in Figure 2 as insets. The anodic peak potentials shifted negatively and broadened as the pH increases, revealing that the electrocatalytic oxidation of MOXI was a pH-dependent reaction with participation of protons
(Ocana
et
al.,
2000)
and
that
the
proton-transfer
reaction
precedes
the electron transfer (Zuman, 1969), i.e. two electrons transferred per molecule (Berg et al., 1981).
As
can
be
seen,
the
peak
current
of
the
formed
complex
increases
on going from pH 2.0 to 6.0. At pH 7.4, the peak current is maximized and then at higher pH values the current decreases abruptly. This approves the predictable performance of protondependent method with irreversible chemical reaction (Zhang and Wei, 2007). As MOXI has a pKa value of 6.25 and 9.29 (Langlois et al., 2005), thus, the chosen pH value of 7.4 adequately brackets the area near the first dissociation of MOXI. 3.3.2. Effect of scan rate and electroactive area calculation A study for a scan rate effect on the anodic peak current of 1.0 mM MOXI has been done by cyclic voltammetry method [See Supplementary material (Figure 1)]. The relation between anodic peak current and the scan rate (ν ranging from 10 to 300 mV/s) gives a linear relationship as shown in the inset. It can be given by the linear equation (Baghayeri et al., 2016): Ip(μA) = 0.89 ν + 34.9 (r = 0.996), which implies that the oxidation process of MOXI is adsorptioncontrolling process (Bard and Faulker, 2001). Also, it is clear that the peak potentials of MOXI are shifted to the positive direction with increasing the scan rate indicating reaction irreversibility (Zuman, 1969). The active surface area of the modified electrode was estimated for a known concentration of K4Fe(CN)6, based on the Randles–Sevcik equation (Roychoudhury et al., 2016): Ip= 2.69 x 015 n3/2 AD1/2 ν
1/2
C, Where Ip is the peak current (A), n is the number of electrons transferred, v is
the scan rate (V s-1), D the diffusion coefficient, A is the electrode area and C is the concentration of K4Fe(CN)6. For 0.0 mmol L-0 K4Fe(CN)6 in 0.10 mol L-0 KCl electrolyte with n = 1 and D = 7.6×10−6 cm s-0 . The area of the bare is 0.07 cm2 and electroactive surface area of SNMCPE was calculated to be 0.125 cm.2
3.3.3. Chronoamperometry [See Supplementary material (Figure 2)] shows the chronoamperometric measurements of MOXI, performed at a constant potential (+940 mV vs. SCE) using SNMCPE in BR buffer (pH = 7.4) containing different MOXI concentrations. Using the Cottrell equation (Bard and Faulkner, 1980), the diffusion coefficient can be calculated
nFAc 0 D i t
(1)
Where i = current, in unit A, n = number of electrons, F = Faraday constant, 96,485 C/mol, A = area of the electrode in cm2, c0 = bulk concentration of the analyte in mol/cm3; D = diffusion coefficient for species in cm2/s and t = time in s. According to the Cottrell equation, the slope obtained from the relation between anodic peak current and t-1/2 (inset) equals nFA (D/π)1/2, so the diffusion coefficient of MOXI was calculated to be 4.376 x 10-6 cm2 s-1. [See Supplementary material (Figure 2 inset)] shows the calibration curve as a linear relationship between different MOXI concentrations (10 to 70 mM) and the current at a fixed time of 2 seconds. The linear equation was Ip(µA)= 7.197C + 1.188 with a correlation coefficient of 0.973. The steady state oxidation current increases with gradual increase in MOXI concentration (Baghayeri et al., 2016). 3.3.4. Effect of repeated CVs
[See Supplementary material (Figure 3)] displays the repeated CVs of 1.0 mM MOXI in BR buffer (pH 7.4), from which, it is clear that the peak current value decreased (inset) from the first scan to the rest scans. This may be due to an adsorption for the oxidation product as an adsorbed film on SNMCPE surface that deactivates and decreases the electroactive surface area of the sensor (Chen et al., 2013). The reproducibility and precision of SNMCPE is performed by repeating the measurement five times that gives relative standard deviation (R.S.D) of 2.16% for the first anodic scan. To attain innovative sensitivity and reproducibility, a first anodic peak current must be recorded for all the analysis in the coming studies. 3.4. EIS measurements
Figure 3: Nyquist plots of MOXI in different pH values using SNMCPE at peak potential. Inset: Nyquist plots of MOXI at Bare CPE and SNMCPE using BR buffer (pH 7.4), at peak potential. Inset: Model used for fitting. Impedance plots are shown as Nyquist plots (Fig. 3 inset) for both the Bare and SNMCPE electrodes. It shows a semicircle corresponds to a charge transfer resistance and a line corresponds to a diffusion process at both high and low frequencies, respectively. The best model
that fits the experiments (Fig. 3 inset) is a one-time constant model consists of Rs (solution resistance), RCT (Charge transfer resistance), W (Warburg impedance) and CPE (constant phase element of capacitance) (Fekry, 2016). The data were simulated to this equivalent circuit model. W is due to the linear region at low frequency (diffusion process) (Fekry et al., 2015, Fekry, 2010), RCT is due to the semicircle at high frequency (charge transfer resistance). A constantphase element (CPE) (Fekry, 2016) was introduced to account for surface non-ideality and heterogeneity, its impedance is ZCPE = [C(jω)α]−1 , where α is due to the surface inhomogeneity ( −1 ≤ α ≤ 1), j is the imaginary number (j2 = -1), ω = 2πf (rad s-1) and f (Hz) is the frequency. Thus, the reaction mechanism depends on both charge transfer and diffusion process (Fekry et al., 2011). The fitting is performed using EC-Lab® software provided with SP-150 workstation. SNMCPE electrode shows higher value for the CPE (5.2 µF cm-2), Warburg impedance (812 Ω cm2 s-1/2) and lower values for the charge transfer resistance (1100 Ω cm2) indicating a higher conductivity compared to the bare electrode with CPE = 3.0 µF cm-2, W = 212 Ω cm2 s-1/2 and RCT = 5300 Ω cm2 . These results approve well the highest oxidation peak current obtained from CVs results to SNMCPE electrode. Also, Nyquist plots (Fig. 3) of MOXI in different pH values using SNMCPE at 940 mV vs. SCE (peak potential) was measured and give the same order of pH obtained from CVs results. The impedance value decreases in the same order as the current increases indicating an increase in the conductivity. This indicates that pH 7.4 is the lowest in impedance value with lower semicircle diameter compared to the bare electrode (inset) and highest conductivity as obtained from CVs results with highest current (Shehata et al., 2016). 3.5. Calibration curve and detection limit
Figure 4: Effect of successive addition of MOXI in BR buffer (pH 7.4) using SNMCPE at a scan rate 10 mV/s. Inset: Calibration curve of MOXI using SNMCPE.
Figure 4 shows CVs of the effect of changing MOXI concentration (7.0×10-7 to 1.8×10-4 M) in BR buffer (pH 7.4) at a scan rate 10 mV/s using SNMCPE. Figure 4 (inset) shows a linear relationship with a linear regression equation: Ip(µA)= 0.0694C + 1.326. The limit of detection (LOD) and limit of quantification (LOQ) were determined according to the IUPAC recommendation (Meier and Zünd , 2000; Fekry et al., 2015) and were found to be 2.9×10-9 M and 9.6 x 10-8 M, respectively. 3.6. Sample analysis
A determination of MOXI in real samples has been performed to estimate the planned method applicability. The established method was tested in Delmoxa tablet (from delta pharma) and human urine sample. Each Delmoxa tablet contains 400 mg MOXI. Five tablets were grinded and weighed to obtain 1.0 mM MOXI solution. Four drug aliquots were presented into the cell and the concentration was determined from the calibration curve. Average concentrations were calculated from five replicate measurements. [See Supplementary material (Table 1)] shows the data generated by standard addition method for the examination of MOXI in buffered solution of pH 7.4. Also, the planned method is right for the quantitative test of the MOXI in urine sample. The calibration curve in Figure 5A gave a straight line with a linear dynamic range 4 x 10-6 M – 1.6 x 10-4 M and LOD = 2.1 ×10−8 M. Four different concentrations are selected to recurring four times to estimate the accuracy and precision of the planned method which is represented in (Table 1). The outcomes displays that the excipient materials in tablets and matrices in urine have no interference in the determination.
Table 1. Evaluation of the accuracy and precision of the proposed method for the determination of (MOXI) in urine sample [MOXI] added (M) x 10-6
[MOXI] Founda
Recovery
SD
S.Eb
C.L.c
(M) x 10-6
(%)
x 10-6
x 10-6
x 10-6
a
5.00
5.22
104.4
0.73
0.41
1.04
50.0
50.09
100.1
0.51
1.31
1.55
100.0
100.6
100.6
1.63
0.77
2.18
160.0
157.05
98.15
1.93
0.98
0.12
mean for five determinations b Standard error = SD/√n c C.L. confidence at 95%confidence level and 4 degrees of freedom (t=2.776)
Figure 5: Calibration curve of MOXI in urine (A). Simultaneous determination of 2 x 10-6 M MOXI and 5 x 10-6 M ACOP (B).
3.7. Simultaneous determination of MOXI and Paracetamol Patient that had high grade fever and dry cough must take 200 mg moxifloxacin orally each 12 hour and 500 mg paracetamol (ACOP) when required (Mandavia et al., 2012). Therefore simultaneous determination of 2 x 10-6 M MOXI with 5 x 10-6 M ACOP in BR buffer (pH 7.4) using SNMCPE at a scan rate 50 mV/s was performed. Figure 5B shows a well separation between ACOP (appears at 580 mV) and MOXI (appears at 940 mV) with ΔE of 360 mV, which indicates the electrocatalytic activity of MOXI and ACOP in the existence of each other. 4. Conclusions A carbon paste sensor with an excellent performance for the electrochemical determination of MOXI built on silver nanoparticles was performed. Silver nanoparticles enhanced the sensitivity of MOXI significantly. The detection limit found to be 2.9×10-9 M. Also, excipients interference of the drugs does not interfere with MOXI. The results showed that the method was easy, cheap, simple and sensitive enough for the determination of MOXI in Delmoxa tablet and human urine under physiological conditions with good precision and low detection limit.
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Highlights
A new simple silver nanoparticle modified carbon paste electrode for MOXI sensing. It gives excellent performance with 2.9×10-9 M detection limit.
The sensor is effective for determination of MOXI in Delmoxa tablet and human urine.