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Ion-selective membrane sensors for the determination of tinidazole and clarithromycin in bulk powder and pharmaceutical formulation

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The construction and electrochemical response characteristics of three selective electrodes were investigated using precipitation based technique with phosphotungstate and phosphomolybdate; respectively upon using polyvinyl chloride (PVC) matrix and dioctyl phthalate (DOP) as a plasticizer. The resultant membrane sensors were tinidazole phosphotungestate (TND-PTA) electrode (sensors 1), tinidazole phosphomolybdate (TNDPMA) electrode (sensors 2) and clarithromycin phosphotungestate (CLR-PTA) electrode (sensors 3). Linear responses of TND and CLR within the concentration ranges of 10−6to 10−2mol/L for sensors 1, 2 and 3 were observed. Nernstian slopes of 58.3, 57.1 and 58.8 mV/decade were observed over the pH range of 3-7 for sensors 1and 2 and over range of 3-8 for sensor 3, respectively. The selectivity coefficients of the developed sensors indicated excellent selectivity for TND and CLR. The proposed sensors displayed useful analytical characteristics for the determination of TND and CLR in bulk powder and pharmaceutical formulation (Helicure® tablets).
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Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572
Full Paper
Ion-Selective Membrane Sensors for the Determination
of Ciprofloxacin Hydrochloride in Water and
Pharmaceutical Formulation
Safaa M. Riad1, Fatma I. Khattab1, Hesham Salem2 and Heba T. Elbalkiny2*
1Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr-El Aini
Street, 11562 Cairo, Egypt
2Analytical Chemistry Department, Faculty of Pharmacy, October University for Modern
Sciences and Arts (MSA), 11787 6th October City, Egypt
* Corresponding Author, Tel.:+201225526650
E-Mail: heba_elbalkiny@hotmail.com
Received: 15 July 2014 / Received in revised form: 9 October 2014
Accepted: 11 October 2014 / Published online: 31 October 2014
Abstract- The construction and electrochemical response characteristics of six
Ciprofloxacin-selective electrodes were investigated using precipitation based technique with
sodium tetraphenyl borate (TPB), phosphomolybdate (PMA) and phosphotungstate (PTA);
respectively upon using polyvinyl chloride (PVC) matrix and dibutyl phthalate (DBP) as a
plasticizer. The resultant sensors have different forms, either as membrane electrodes
(sensors 1, 3 and 5) or as coated wire electrodes (sensors 2, 4 and 6). Linear responses of CIP
within the concentration ranges of 10−6 to 10−2 mol/L for sensors 1, 2 and 5 while for sensors
3 and 4, the linear responses were within the concentration ranges of 10−5 to 10−2 mol/L and
for sensor 6 it shows linear responses within the concentration ranges of 10−7 to 10−2 mol/L.
Nernstian slopes of 51.7, 50.7, 58.3, 57.7, 44 and 41.8 mV/decade were observed over the pH
range of (5–9) for sensors 1, 2, 5 and 6 and over range of (5-7) for sensor 3 and 4
respectively. The selectivity coefficients of the developed sensors indicated excellent
selectivity for CIP. The proposed sensors displayed useful analytical characteristics for the
determination of CIP in water samples and pharmaceutical preparation.
Keywords- Ciprofloxacin HCl, Phosphomolybdic acid, Phosphotungestic acid, Tetraphenyl
borate, Water samples
Analytical &
Bioanalytical
Electrochemistry
© 2014 by CEE
www.abechem.com
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 560
1. INTRODUCTION
Pharmaceutical compounds are widespread contaminants of the aquatic environment.
Since traditionally they have not been viewed as environmental contaminants, the study of
their presence in the environment is in some ways a new area of research which has taken
recent years. Our current knowledge indicates that residues of pharmaceuticals at trace
quantities are widely spread in aquatic systems [1]. Antibiotics constitute a large group of
pharmaceuticals, which are widely administered in human and veterinary medicine. The
extensive use of these antibiotics may result in their presence in the environment. Antibiotics
are believed to be of greatest concern among all pharmaceuticals due to the potential risk of
antibiotic resistance. Studies in the United States of America and Europe have detected
antibiotic resistant bacteria in drinking water supplies [2,3]. According to previous studies
and publications, one of the most prevalent groups of antibiotics found in the environment,
and particularly in surface waters, is that of the widely used, highly potent fluoroquinolones
[4,5]. They are largely excreted as unchanged compounds in urine, and consequently
discharged into hospital sewage or municipal wastewater. Despite lots of studies with
positive detection of antibiotics and other pharmaceuticals in soils and environmental waters
and despite of their negative effects on human health, there is no defined limit value for the
occurrence of these pollutants in soils or natural waters [6].
Therefore, more monitoring and surveillance studies are needed at local level to
determine exactly how the antibiotics make their way into public waterways, and to obtain a
better understanding of the transport and environmental fate of antibiotics.
Ciprofloxacin HCL (CIP) is 1-Cyclopropyl–6–fluoro–1,4–dihydro–4–oxo–7-(1–
piperazinyl)-3–quinolone carboxylic acid it is a bactericidal fluoroquinolone. It acts by
inhibiting the A subunit of DNA gyrase (topoisomerase) which is essential in the
reproduction of bacterial DNA [7], its chemical structure was shown in Fig. 1.
Different analytical techniques were reported for CIP determination in pharmaceutical
preparations, biological fluids and waste water such as: Spectroscopic methods [8-11],
spectrofluorimetric methods [11-13], TLC [14,15], HPLC [6,16-19], Capillary
electrophoresis [20], ion selective electrode [21-24].
Here in we report the novelty of electrochemical determination of CIP in production
waste water sample by using the developed sensors without the need of preliminary
extraction or cleaning up procedures of the samples.
The developed sensors were also successfully applied for the electrochemical
determination of ciprofloxacin hydrochloride in pharmaceutical formulation. The method has
the advantages of high sensitivity, accuracy, selectivity and the possibility of direct
determination of the drug in turbid and colored solutions.
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 561
N
COOH
O
F
N
HN
.HCl
(C17H18FN3O3•HCl, formula weight 367.8 g/mol)
Fig. 1. Structural formula of ciprofloxacin hydrochloride
2. EXPERIMENTAL
2.1. Apparatus
A Jenway digital ion analyzer model 3505 (Jenway, UK) with Ag/AgCl double junction
reference electrode (Aldrich, USA) was used for potential measurements. A Jenway pH glass
electrode (Jenway, UK) was used for pH adjustments.
2.2. Chemicals and Reagents
2.2.1. Pure Sample
Ciprofloxacin HCl powders were kindly supplied by Egyptian pharmaceutical industrial
company (EPICO, EGYPT) and its percentage purity was found to be 100.1±0.95, according
to official BP methods [25].
2.2.2. Chemicals and Reagents
All chemicals and reagents used were of analytical reagent grade. Polyvinyl chloride
(PVC), Phosphomolybdic acid (PMA), Phosphotungestic acid (PTA), Sodium tetraphenyl
borate (TPB), Dibutyl phthalate (DBP) and Tetrahydrofuran (THF) were obtained from
Aldrich, USA. Hydrochloric acid, sodium hydroxide scales, potassium chloride were
obtained from El-Nasr pharmaceutical chemicals, Cairo, Egypt. Starch, Lactose, CaCl2,
NaCl, Glucose and Urea were obtained from Adwic, Cairo, Egypt.
2.3. Standard solutions
2.3.1. Stock Solutions
CIP was freshly prepared by transferring 0.1839 g of ciprofloxacin hydrochloride into a
50-ml volumetric flask. It was dissolved in 20 mL bi-distilled water, and the volume was then
completed with the same solvent and protected from light.
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 562
2.3.2. Working solutions (1×10--1×10-7M)
Different solutions were freshly prepared by serial dilution from the stock solution using
bi-distilled water. The prepared solutions were kept in well-closed tight containers and
protected from light.
2.4. Procedures
2.4.1. Sample Collection and Preparation
A total of six wastewater samples were collected from pharmaceutical industries at
different sites as shown in Table 1 and placed in 2 L amber glass bottles, Water samples were
filtered through 0.45µm nylon membrane filter to eliminate fine particulate matter, and stored
in the dark at 4C to avoid any degradation or deterioration [18].
2.4.2. Precipitation of the Ion Exchangers
In two different beakers, ten ml aliquot of 10-2 M aqueous standard CIP solution was
treated separately with 10 ml of aqueous 10-2 M of each of TPB, PMA and PTA solutions,
respectively. The prepared solutions were shaken well for 5minutes. The precipitates formed
were filtered using Whitman filter papers, washed with cold water till chloride free (tested by
AgNO3 solution), dried at room temperature (~25°C) and then ground to fine powder. The
formation and purity of the ion-associates and the chemical compositions of the precipitates
were checked by elemental analysis for carbon, hydrogen and nitrogen, IR and mass
spectroscopy.
2.4.3. Fabrication of PVC Based Membrane Sensors
For the preparation of sensor 1, 3 and 5, amounts of 10 mg of ion exchangers were
separately mixed with 0.35 ml of DBP and 0.19 g PVC respectively in three separate glass
petri dish (5 cm diameter), and then the mixtures were dissolved in 5 ml THF. The petri
dishes were covered by a filter papers and left to stand overnight to allow solvent evaporation
at room temperature. These ratios of components added will form a master membrane with a
thickness of 0.1 mm which is wanted. From the formed master membranes, disks (10 mm
diameter) were cut using a cork borer and pasted using THF to interchangeable PVC tips that
were clipped into the end of the electrodes glass bodies. Equal volumes of 10-2 M CIP and
10-2 M KCl were mixed and this obtained solution was used as an internal reference solution.
Ag/AgCl wire (1mm diameter) was immersed in the internal reference solution as an internal
reference electrode. The electrodes were preconditioned by immersing in 10-2 M CIP solution
for 24 h. The electrochemical cell for potential measurements was: Ag/AgCl (internal
reference electrode)/ 1.0×10-2 M CIP solution, 1.0×10-2 M KCl (internal reference
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 563
solution)//PVC membrane//test solution (pH 4-9)//Ag/AgCl double junction reference
electrode. The sensors were stored in distilled deionized water between measurements.
2.4.4. Fabrication of PVC Based Coated Wire Electrode
The previously prepared (CIP–ion exchangers, DPB, PVC and THF) mixtures were left at
room temperature to allow solvent evaporation to obtain colloidal solutions. Three electrodes
were prepared by applying layers of the pervious mixtures onto a silver wires tip at
10minutes interval until a globular membrane of about 3 mm diameter around the wire ends
were formed. The electrodes were left standing at room temperature for 24 h to dry. The
resultant dry coated wires membrane sensors had to be conditioned by soaking in 1.0×10-2 M
CIP for 3 h and stored in the same solution when not in use. The electrochemical cell for
potential measurements was: silver wire//PVC membrane//test solution (pH 4-9)//Ag/AgCl
double junction reference electrodes.
2.4.5. Sensors Calibration
The conditioned sensors were calibrated by separately transferring 50 ml aliquots CIP
solutions prepared in distilled water with concentration range of (1×10-7–1×10-2 M) into a
series of 100 ml beakers starting from the low to the high concentrations. The membrane
sensors in conjunction with a reference electrode were immersed in each solution, allowed
equilibrating with constant stirring using a magnetic stirrer, then recording the stable
potential within ±2 mV. The electrode potential (EMF) was plotted versus each negative
logarithmic concentration of CIP. The response time of the investigated electrodes was
calculated.
2.4.6. Effect of pH
The effect of pH on the potential values of the four investigated sensors was studied over
pH range of 3-10 at 1 pH interval by using 10-4 M and 10-3 M CIP solutions. The pH was
gradually increased or decreased by adding aliquots of dilute sodium hydroxide or dilute
hydrochloric acid solutions respectively. The potential obtained at each pH value was
recorded.
2.4.7. Sensors Selectivity
The potentiometric selectivity coefficient log K pot. (Primary ion, interferent) was used to
evaluate the extent to which a foreign ion would interfere with the response of an electrode to
its primary ion. Selectivity coefficients were calculated by the separate solutions method,
where potentials were measured for 10-3 M aqueous CIP solution and then for 10-3 M aqueous
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 564
interferent solution separately then potentiometric selectivity coefficients were calculated
using the following equation:
log, =–
+1 −
log (1)
Where K pot A.B is the potentiometric selectivity coefficient, EA and EB are the potentials of
the drug and the interfering solutions respectively, S represents the slope of the calibration
plot, aA is the activity of the drug, ZA and ZB are the charges on the drug and the interfering
ions, respectively.
2.4.8. Application to Pharmaceutical Dosage Forms
2.4.8.1. Ciloxan Eye Drops®
Five milliliters of Ciloxan® eye drops 0.3%were transferred into 50 mL volumetric flask,
the volume was completed with distilled water to get 300 µg mL-1 of CIP. The potentiometric
measurements were performed using the proposed sensors in conjunction with the Ag/AgCl
reference electrode, and the potential readings were compared to the calibration plots.
2.4.9. Determination of CIP in Spiked Water Samples
Volume of 2.5 mL of 10-3 M standard drug solution was added into 50 mL beaker
containing 22.5 mL of the filtered water, and vortex for 1 min. The membrane sensors were
immersed in conjunction with the reference electrode in this solution and then washed with
water between measurements. The emf value of this spiked water sample was measured by
the proposed sensors, and the concentration of CIP was calculated from the corresponding
regression equation.
3. RESULTS AND DISCUSSION
The present work evaluated the possibility of quantitative determination of CIP by using
selective membrane sensors with ion exchanger TPB, PMA and PTA in its composition using
PVC as a polymeric matrix to immobilize the sensors and to attain the formation of highly
stable complexes. It was found that the three ionic exchangers have low solubility product
and suitable grain size. CIP was found to form 3:1 ion association complex with a PTA, 3:1
with PMA and 1: 1 with TPB as proven by elemental analysis (as monovalent cation) and the
obtained Nernstian slopes as mentioned in Table 1 and also using IR as shown in Fig. 2. The
proposed sensors were used for the determination of CIP in bulk powder, pharmaceutical
formulations and in water samples such as wastewater from pharmaceutical companies.
One of the problems in the determination of antimicrobials in the aquatic products is the
sample treatment, due to the presence of other organic contaminants in the matrix, which can
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 565
interfere with the analytical procedures. It was found that ion selective electrodes (ISEs) offer
several advantages over other methods for environmental analysis [26], particularly its ability
for direct measurements in troubled, viscous solutions and in complex matrices without the
need for samples pretreatment. In addition to its expense is considerably lowered than of the
other methods, easy to use, time saving and non-destructive.
(a)
(b)
(c)
Fig. 2. Profile of IR of ion association complexes of CIP with (a) TPB, (b) PTA and (c) PMA
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 566
Table 1. Elemental analysis of the ion-associates
Ion
associates Tentative formulae Percentage C% H% N%
CIP-TPB (C17H18FN3O3)(C6H5)4B Found 75.83 5.94 6.57
Calculated 75.69 5.89 6.46
CIP-PMA (C17H18FN3O3)(H3PMo12O40)
Found 21.23 2.18 4.42
Calculated 20.9 2.15 4.3
CIP-PTA (C17H18FN3O3)( H3PW12O40) Found 15.58 1.37 3.23
Calculated 15.5 1.4 3.26
3.1. Performance Characteristics of CIP Sensors
The electrochemical performance characteristics of the investigated CIP–selective sensors
were evaluated according to the IUPAC recommendation data [27] and it was summarized in
Table 2. It has been reported that PVC matrix is a regular support and reproducible trap for
ion association complexes in membrane sensors. Nevertheless, its use creates a need for
plasticization and places a constraint on the choice of mediator [28].
Table 2. Electrochemical response characteristics of the six proposed sensors used for the
determination of ciprofloxacin hydrochloride
Parameters Sensor1 Sensor 2 Sensor 3 Sensor 4 Sensor 5 Sensor 6
Slope (mV/decade)
a
-51.7 -50.7 -58.3 -57.7 -44 -41.8
Intercept (mV) 101.4 87.3 158.8 162.7 181.2 180.19
LOD ( mol. L
-
1
)
b
3×10
-
7
10
-
7
2×10
-
5
10
-
5
3×10
-
6
9×10
-
6
Response time (s) 10 10 15 15 10 10
Working pH range 5-9 5-9 5-7 5-7 5-9 5-9
Concentration range
(M) 10-2-10-6 10-2-10-6 10-2-10-5 10-2-10-5 10-2-10-6 10-2-10-7
Stability (weeks) 4 weeks 4 weeks 4 weeks 4 weeks 5 weeks 5 weeks
Average recovery (%)
± S.Da 99.9±2.09 101±1.154 100.55±1.884 99.68±2.2 99.8±1.39 100.2±1.433
Correlation
coefficient (r) 0.9987 0.997 0.9976 0.997 0.999 0.9974
a Result of five determinations
b Limit of detection ( measured by interception of the extrapolated arms of figure 2)
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 567
In the present study, the use of the plasticizers, dibutyl phthalate (DBP) has been used in the
fabrication of the proposed membrane sensors sensor. It adjusted the permittivity of the final
organic membranes and mobility of the ion exchanger sites. The membranes constituents
were dissolved in THF that was slowly evaporated at room temperature leading to membrane
formation. Sensor 6 showed best sensitivity, where linearity was obtained in the range of (10-
2–10-7 M); sensors 1, 2 and 5showed also good sensitivity as their linearity was in range of
(10-2–10-6 M); while sensors 3 and 4 fell short in the limit of linearity (10-2–10-5 M). Sensors
1, 2, 3 and 4 had good slope 51.7, 50.7, 58.3 and 57.7mV/decade, while the slopes of the
calibration plots were 44 and 41.8 mV/decade for sensors 5 and 6, respectively. Typical
calibration plots are shown in Fig. 3. Deviation from the ideal Nernstian slope (60 mV) is due
to the electrodes responding to the activity of the drug cations rather than its concentration.
The sensors displayed constant potential readings for day to day measurements, and the
calibration slopes did not change by more than ±2 mV/decade over a period of 28 days. The
detection limits of the three sensors were estimated according to the IUPAC definition [27].
The slopes of the calibration plot did not change significantly but show a gradual decrease in
sensitivity.
Fig. 3. Profile of the potential in mV to -log concentration of CIP using the two proposed ion
selective electrode method
3.2. Dynamic Response Time
Dynamic response time is an important factor for analytical applications of ion-selective
sensors. In this study, practical response time was recorded b y increasing CIP concentration
by up to 10-fold. The required time for the sensors to reach values within ±2 mV of the final
-250
-200
-150
-100
-50
0
50
100
150
0 2 4 6 8 10
E(mv)
- log Conc mol/L
Series1
Series2
Series3
Series4
Series5
Series6
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 568
equilibrium potential was 10-15 sec. for the sensors. The response time increases with
increasing the concentrations.
3.3. Effect of pH
For quantitative measurements with ion selective electrodes, studies were carried out to
reach the optimum experimental conditions. The potential pH profile obtained indicated that
the responses of the sensors 1, 2, 5 and 6 were fairly constant over the pH range 5–9; at pH
less than 4 drop in reading occurs. Therefore, the pH range from 5 to 9 was assumed to be the
working pH range of these sensors. While for sensor 3 and 4, the constant working pH is 5-7
as less than 5 and more than 7 potential readings were not constant as shown in Fig. 4.
Fig. 4. Effect of pH on the response of the six sensors at 10-3 M and 10-4 M
3.4. Sensors Selectivity
Sensors 5 and 6 showed the highest selectivity coefficient values that correspond with
more attack by interfering cations on the electrode membrane. The higher the selectivity
coefficient value, the more the electrode membrane is attacked by the interfering cations.
Table 3 shows the potentiometric selectivity coefficients of the proposed sensors in the
presence of other pharmaceutical contaminants and inorganic cations (K+, Na+ and Ca2+) that
are usually found. Glucose, lactose and starch those are usually present in dosage forms. The
-140
-120
-100
-80
-60
-40
-20
0
20
40
60
0 2 4 6 8 10
E(mv)
pH
sensor1 10
-
3 M
sensor 1 10
-
4 M
sensor 2 10
-
3 M
sensor 2 10-4 M
sensor 3 10
-
3 M
sensor 3 10
-
4 M
sensor 4 10
-
3 M
sensor 4 10-4 M
sensor 5 10-3 M
sensor 5 10
-
4 M
sensor 6 10
-
3 M
sensor 6 10
-
4 M
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 569
results reveal that the proposed membrane sensors display high selectivity; sensors 3 and 4
are at least 10 times more selective than sensors 1 and 2.
Table 3. Potentiometric selectivity coefficients of by separate selectivity method (SSM)
Interferenta
Selectivity coefficient
b
Sensor1 Sensor 2 Sensor 3 Sensor 4 Sensor 5 Sensor 6
NaCl 1.8×10
-
2
1.4×10
-
2
2.7×10
-
3
2.5×10
-
3
3×10
-
3
2.32×10
-
3
Glucose 1.9×10
-
2
1.3×10
-
2
5.8×10
-
3
5.3×10
-
3
1.4×10
-
2
1.7×10
-
2
Urea 2.4×10
-
2
1.4×10
-
2
9.8×10
-
3
9×10
-
3
5.3×10
-
3
5.6×10
-
3
Lactose 4.6×10
-
2
2.8×10
-
2
2.8×10
-
2
2.6×10
-
2
5.9×10
-
3
6.3×10
-
3
CaCl2 1.5×10
-
2
1.06×10
-
2
2.67×10
-
2
2.4×10
-
3
3.3×10
-
3
3.9×10
-
3
Starch 1.2×10
-
2
1.68×10
-
2
1.2×10
-
2
1.19×10
-
2
3.6×10
-
3
4.02×10
-
3
KCl 1.6×10
-
2
1.06×10
-
2
3. 25×10
-
3
2.7×10
-
3
4.3×10
-
3
3.2×10
-
3
a Aqueous solutions of 1×10-3 M were used
b Each value is the average of three determinations
3.5. Potentiometric Determination of CIP in Pharmaceutical Formulations
The proposed sensors were applied for the analysis of CIP pharmaceutical formulations in
buffered solutions. The results prove the applicability of the six sensors for the determination
of pharmaceutical formulations containing CIP. These data are shown in Table 4. To examine
the validity of the proposed sensors, the obtained results were compared to HPLC method
and no significant difference was observed. Moreover, the proposed Sensors do not require
preliminary drug extraction.
Table 4. Determination of Ciprofloxacin hydrochloride in pharmaceutical formulation by the
six proposed sensors
Pharmaceutic
al preparation
Added
R%±
SD*
Ciloxan 0.3%
8.13×10
-
4
M
Sensor 1
Sensor 2
Sensor 3
Sensor 4
Sensor 5
Sensor 6
102.21±
0.21
101.7
0
±
0.25
102.09
±
0
.
3
1
100.91
±
0.34
101.2
0
±
0.36
100.2
0
±0.76
* Average of three determinations
3.6. Potentiometric Determination of CIP in Water Samples
For determination of CIP in spiked wastewater sample (as concentration of CIP may be
lower than LODs of the used sensors), it was found that four of the six sensors (sensor 1, 3, 5
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 570
and 6) are reliable and give stable results with very good accuracy and high Percentage
recovery without preliminary extraction procedures, that’s due to their low LODs which is
shown in Table 5. The pH of these samples was measured and was found to be 6.2±0.5,
which is within the pH working range of the proposed sensors.
The response times of the proposed sensors are instant (within 15 s). It is concluded that
the proposed four sensors can be successfully applied in environmental analysis.
Statistical comparison was done between the proposed sensors and the official method,
and no significance difference was observed as shown in Table 5. One way ANOVA was
performed to prove that no significance difference was present between the results of the
proposed sensors (Table 6 and 7).
Table 5. Determination of Ciprofloxacin hydrochloride in spiked wastewater samples by the
six proposed sensors
Added (ppm) R% ± SD*
1×10
-
4
M (36.78)
Sensor 1 Sensor 2 Sensor 3 Sensor 4 Sensor 5 Sensor 6
104.23±1.34 118±2.3 101.6±2.04 102±1.87 96.5±1.4 94.1±1.87
* Average of three determinations
Table 6. Statistical comparison of the results obtained by the proposed sensors and the
official method on pure form
Items Official
Method Sensor 1 Sensor 2 Sensor 3 Sensor 4 Sensor 5 Sensor 6
Mean 100.206 99.94 101.33 100.55 99.83 99.85 100.2
± SD 0.9502 2.051 1.153 1.884 2.2 1.396 1.434
Variance 0.902 4.206 1.3317 3.55 4.48 1.9488 1.96
n 5 5 5 4 4 5 5
SEM
0.425 0.9353 0.516 0.9421 1.126 0.6243 0.6412
Student’s
t-test
(2.306)b
0.2502 1.692 0.3638
(2.364)b
0.3617
(2.364)b 0.4594 0.0072
F
value
(6.3882)b 4.844 1.475 3.932
(6.5914)b
5.614
(6.5914)b 2.158 2.276
a BP method is HPLC method.
b Figures between parentheses represent the corresponding tabulated values of t and F at P=0.05
Anal. Bioanal. Electrochem., Vol. 6, No. 5, 2014, 559-572 571
Table 7. ANOVA for the proposed methods for the determination of CIP in pure form
Source of Variation Degree of
freedom
Sum of
Squares Mean square F critical F
Between Groups 6 8.984936 1.497489 2.49041 0.424685
Within Grou
ps
25 88.15286 3.526114
Total 31 97.1378
4. CONCLUSION
The described sensors are sufficiently simple and selective for the quantitative
determination of CIP in pure form, pharmaceutical formulations and water samples. PTA as
ionophores increased the membrane sensitivity of sensors 5 and 6 in comparison with other
sensors. High selectivity and rapid response make these electrodes suitable for measuring the
concentration of ciprofloxacin hydrochloride in a wide variety of samples without the need
for pretreatment or clean up steps and without significant interference from other anionic or
cationic species present in the waste water.
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