Materials Science and Engineering C 49 (2015) 445–451

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A new approach for decreasing the detection limit for a ketamine(I) ion-selective electrode Hazem M. Abu Shawish a,⁎, Hassan Tamous b, Salman M. Saadeh c, Khalid I. Abed-Almonem d, Osama Al khalili e a

Chemistry Department, College of Sciences, Al-Aqsa University, Gaza, Palestine Chemistry Department, Al-Azhar University, Gaza, Palestine Chemistry Department, College of Sciences, The Islamic University, Gaza, Palestine d Ministry of Education, Gaza, Palestine e Ministry of Health, Public Heath Lab, Gaza, Palestine b c

a r t i c l e

i n f o

Article history: Received 18 August 2014 Received in revised form 15 December 2014 Accepted 4 January 2015 Available online 6 January 2015 Keywords: Ion-selective electrode PVC membrane electrode Ketamine hydrochloride Ion-pair

a b s t r a c t Our endeavors of lowering the detection limit for a ketamine(I) ion-selective electrode were described. The paper stresses the electrode which showed best results for determination of ketamine ion. The present electrode incorporates ketamine-phosphomolybdate (KT-PM) as ion-exchanger combined with the lipophilic anionic additive (Na-TPB) dissolved in dibutyl phthalate (DBP) as a plasticizer. The characteristics of the electrode were elaborately measured and its performance was tested in various samples and urine. It has favorable features as it provides measurements of the potential with a near-Nernstian slope of 56.6 ± 0.3 mV/decade over the concentration range of 1.5 × 10−6–1.0 × 10−2 M over the pH range 3.0–6.8 in a short response time (7 s). Importantly, it has a low detection limit of 1.2 × 10−7 M and its life-span is 22 days. Moreover, it displayed notable selectivity for ketamine ion over other species such as inorganic and organic cations and different excipients which may be present in pharmaceutical preparations. The sensor was applied for determination of KT ions in urine and pharmaceutical preparations using potentiometric determination, standard addition and the calibration curve methods. The standard deviation computed on the results indicated excellent repeatability of the measurements. Overall, it showed satisfactory results with excellent percentage recovery comparable to and sometimes better than those obtained by other routine methods for the assay. © 2015 Elsevier B.V. All rights reserved.

1. Introduction Ketamine (KT) is metabolized to norketamine (NK) which is then dehydrogenated to dehydronorketamine (DHNK). KT, NK and DHNK are hydroxylation and conjugated before elimination. A mixture of the drug and its metabolites are excreted. KT and NK are the target analytes in toxicological analysis and DHNK is a biomarker of administration of KT in the literature [1–3]. Ketamine, (2-chlorphenyl)-2-(methylaminocyclohexanone), is a colorless, odorless, tasteless, hallucinogenic and anesthetic commonly used for animals and humans. It is used by youth in recreational parties for sedation and misused in drug-facilitated crimes for its pharmacological properties [1]. Thus, there is a critical need for the development of selective, inexpensive diagnostic tool for the determination of this analyte. Several analytical methods for the determination of KT are known such as the electrochemical method [4], micellar electrokinetic chromatography (MEC) [5],gas chromatography with flame-ionization detector (GC–FID) [6],nitrogen–phosphorus detector (GC–NPD) [7], highperformance liquid chromatography (HPLC) [8], gas chromatography– ⁎ Corresponding author. E-mail address: [email protected] (H.M. Abu Shawish).

http://dx.doi.org/10.1016/j.msec.2015.01.010 0928-4931/© 2015 Elsevier B.V. All rights reserved.

mass spectrometry (GC–MS) [9–11], liquid chromatography–mass spectrometry (LC–MS) [12,13] and solid-phase extraction (SPE) [14–19]. In addition, polyvinylidene difluoride (PVDF) filter syringes [20] and solidphase microextraction (SPME), liquid-phase microextraction (LPME) [21,22] as well as potentiometric method [23] are in use. However, most of these methods require sample manipulations that are liable to various interferences as well as being not applicable to colored and turbid solutions. Furthermore, these methods are expensive for they require large infrastructure backup and qualified personnel. Thus, the development of selective and inexpensive diagnostic tool for the determination of this analyte is badly needed. Potentiometric methods employing ion-selective electrodes (ISEs), as one of the most important groups of chemical sensors, are good alternatives for their attractable characteristics such as simple design, ease of fabrication, good selectivity, short response time and applicability to miscellaneous analytes thus providing possible interfacing with automated and computerized systems and making the use of ISEs pervasive in pharmaceutical science among various applications [24–26]. The mechanism of the potential formation of ion-selective electrodes with a liquid polymeric membrane depends strongly on extraction and ion-exchange processes between the aqueous and organic phases [27]. The organic phase must be homogeneous, compatible with the other membrane components

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and acts as a plasticizer whose polarity and dielectric constant influence the ion-pair characteristics of the membrane and consequently its selectivity [28]. Na-TPB is commonly used as a lipophilic anionic additive in polymeric membrane-based potentiometric electrodes selective for cations to reduce the membrane resistance, improve the behavior and selectivity and in some cases, where the extraction capability is poor, and increase the sensitivity of the membrane sensor [29,30]. Careful review of the literature spotted a report [23] on an electrode for determination of ketamine. In line with the same approach, we developed a new electrode with characteristics that surpass those of that electrode. We studied the selectivity of the electrode for ketamine as opposed to similar medicines in use and over excipients commonly comprised in this medication. The results indicate better selectivity of the present electrode where the selectivity coefficient values for common ions were an order of magnitude smaller than those of the reported electrode. In addition, the detection limit of the present electrode is smaller (1.2 × 10−7 M vs. 5 × 10−6 M) and it spans a wider concentration range (1.5 × 10−6–1.0 × 10−2 M vs. 1.0 × 10−5–1.0 × 10−2 M) of measurements in a short response time (7 s. vs. 10 s.). This paper describes utilization of some ion-pairs, ketaminium phosphotungstate (KT3-PT), ketaminium phosphomolybdate (KT3-PM), ketaminium tetraphenylborate (KT-TPB), a lipophilic additive Na-TPB and a few plasticizers dibutyl phthalate (DBP), dioctyl phthalate (DOP), dioctyl sebacate (DOS), tris(2-ethylhexyl)phosphate (TEPh), to optimize the membrane response. With the current electrode, comprising KT-PM, NaTPB and DBP, a drop in the detection limit by an order of magnitude was attained (from 10−6 to 10−7). 2. Experimental 2.1. Reagents All reagents used were chemically pure grade. Doubly distilled water was used throughout all experiments. Ketamine (ketamine hydrochloride) KTCl (Fig. 1); [2-(2-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride] [6740-88-1] (chemical formula C13H16CINO·HCl, CAS: 6740-88-1, molecular weight = 274.19 g/mol), its pharmaceutical preparations (ampules 50 mg/mL), was provided by General Administration of Pharmacy (Ministry of Health, Gaza, Palestine). Phosphotungstic acid (PTA) H3[PW12O40] M. wt. 2880, phosphomolybdic acid (PMA) H3[PMo12O40] M. wt. 1825, and sodium tetraphenylborate (Na-TPB) Na [C24H20B] M. wt. 342 were obtained from Sigma. Dibutyl phthalate (DBP), dioctyl phthalate (DOP), dioctyl sebacate (DOS), tris(2-ethylhexyl)phosphate (TEPh), polyvinyl chloride (PVC) of high relative molecular weight and tetrahydrofuran (THF) were obtained from Aldrich chemical company. In addition, glucose, galactose, fructose, sucrose, ceftriaxone sodium, ampicillin sodium, gentamycin sulfate, hydrocortisone sodium, lasix and diclofenac sodium were obtained from local drug stores. 2.2. Apparatus

(WTW)-Germany) under stirring conditions at room temperature (25.0 ± 0.1 °C). Saturated calomel electrode (SCE) was used as a reference electrode for potential measurements and was obtained from SigmaAldrich Co. (St Louis, MO, USA). The emf measurements with the proposed electrode were carried out with the following cell notations: Ag-AgCl║internal solution 10-2M KCl and 10-3 M KTCl║PVC membrane ║ sample solution ║ Hg,Hg2Cl2(s), KCl (sat.).

2.3. Preparation of the ion-pairs An ion-pair was made from KTCl and one of the following substances according to a reported method [31,32]: (PTA), (PMA) or (Na-TPB) as detailed below: The ion-pairs, (KT3-PT), (KT3-PM) and (KT-TPB), were prepared by addition of 10 mL of 0.01 M KTCl solution to 10 mL of 0.0033 M of (PTA), 0.0033 M of (PMA) and 0.01 M of (Na-TPB). The resulting precipitates were left overnight to assure complete coagulation. The precipitates were then filtered and washed thoroughly with 50 mL of distilled water. The filter paper containing the precipitate was dried at room temperature for 24 h and ground to fine powders. These ion-pairs were used as the active substances for preparing the electrodes of ketamine hydrochloride.

2.4. Preparation of PVC membrane electrodes Membranes of different compositions were prepared. The percentages of each ion-exchanger were changed to cover the ranges of 0.1– 1.0% (w/w). The membranes of optimum composition were prepared by dissolving the required amounts of PVC and one of the plasticizers in 5 mL THF. The calculated amount of ion-pair was mixed with the PVC and plasticizer solution in Petri-dish (5.0 cm diameter). The total weight of constituents in each batch is fixed at 0.30 g. To obtain homogenous and uniform thickness, the membranes were left to dry freely in air (not less than 24 h). In each case, after curing small disks (7.5 mm) were punched from the cast films and mounted in a homemade electrode body (Scheme 1). The electrodes were filled with a solution that is 10−2 M with respect to KCl and 10−3 M with respect to ketamine hydrochloride solution and preconditioned by soaking in 10−3 M of the ketamine hydrochloride solution.

2.5. Construction of the calibration curve Suitable increments of standard drug solutions were added to 50 mL doubly distilled water that cover the concentration range 1.0 × 10−7 M– 1.0 × 10−2 M. The sensor and the reference electrode were immersed in the solution at 25 ± 1 °C, after each addition. The emf values were plotted versus the negative logarithm of the drug concentration (pKT).

Potentiometric measurements were carried out with a digital millivoltmeter (SR-MUL-3800). pH measurements were made with a digital pH meter (Wissenschaftlich-Technische Werkstatten GmbH

Fig. 1. The chemical structure of ketamine hydrochloride.

Scheme 1. Schematic diagram of PVC membrane electrode.

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2.6. Effect of temperature on the electrode potential To study the thermal stability of the electrode, calibration curves were constructed at different test solution temperatures covering the range 25–55 °C. The slope and usable concentration range of the electrode were determined at each temperature. 2.7. Effect of pH on the electrode potential

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where Cx is the concentration to be determined, Vx is the volume of the original sample solution, Vs and Cs are the volume and concentration of the standard solution added to the sample to be analyzed, respectively, ΔE is the change in potential after addition of certain volume of standard solution, and S is the slope of the calibration curve. 2.9.3. Potentiometric titration Potentiometric titration of 5 mL and 10 mL of 1.0 × 10−2 M KTCl solution was transferred to a 25 mL beaker and titrated with a standard solution of Na-TPB, using the prepared KT sensor as an indicator electrode. The end points were determined from the S-shaped curve.

The effect of pH of the test solution on the potential of the electrode system in solutions of different concentrations (1.0 × 10− 3 M and 1.0 × 10− 4 M) of the pharmaceutical compound was studied. Aliquots of the drug on (50 mL) were transferred to 100 mL titration cell and the tested electrode in conjunction with the SCE and a combined glass electrode were immersed in the same solution. The pH of the solution was varied over the range of 2.0–9.0 by addition of very small volumes of (0.1 or 1.0 M) HCl and/or NaOH solution. The mV-readings were plotted against the pH-values of the different concentrations.

2.9.4. Analysis of ketamine hydrochloride in spiked urine samples Urine samples (5.0 mL) were spiked with ketamine hydrochloride and stirred for 5 min, prior to transferring to a 25-mL volumetric flask. Volume was completed to the mark to give 1.0 × 10− 5 M and 2.0 × 10− 4 M ketamine hydrochloride. Solution was analyzed using either the standard additions or the calibration graph method for KTCl determination.

2.8. Effect of interfering ions

3. Results and discussion

Potentiometric selectivity factors of the electrode were evaluated by applying the matched potential method (MPM) and the separate solution method (SSM) [33]. According to the MPM, the activity of KT (I) was increased from aA = 1.0 × 10− 5 M (reference solution) to ãA = 5.0 × 10−5 M, and the change in potential (ΔE) corresponding to this increase was measured. Next, a solution of an interfering ion of concentration aB in the range 1.0 10−1–1.0 × 10−2 M is added to the new 1.0 × 10−5 M (reference solution) until the same potential change (ΔE) was recorded. The selectivity factor for each interferent was calculated using Eq. (1):

3.1. Composition of membranes

Pot

K KT;

J Zþ

¼

aKT : aJ

ð1Þ

In the SSM [33], the potential of a cell comprising a working electrode and a reference electrode is measured in two separate solutions, one containing the ketamine ions, E1, and the other containing the interferent ions (J), E2, and S is the slope of the calibration graph. These values were used to calculate the selectivity coefficient from the following equation: pot

log K Drug; J 2þ ¼

h i1=z E2 −E1 zþ þ log ½Drug − log J : S

ð2Þ

2.9. Analytical application 2.9.1. Calibration graph method In the calibration curve method, different amounts of KTCl were added to 50 mL of water comprising a concentration range from 1.0 × 10−7 M to 1.0 × 10−2 M and the measured potential was recorded using the present electrode. Data were plotted as potential versus logarithm of the KT+ activity and the resulting curve was used for subsequent determination of unknown drug concentration. 2.9.2. Standard addition method Small increments of a standard KTCl solution (1.0 × 10−2 M) were added to 25 mL aliquot samples of various drug concentrations (1.0 × 10−5 M and 5.0 × 10−4 M). The change in mV reading was recorded for each increment and used to calculate the concentration of the drugs in sample solution using Eq. (3):  Cx ¼ Cs

Vs Vx þ Vs

 nðΔE=SÞ − 10

Vx Vs þ Vx

−1

ð3Þ

On using an ion-selective electrode in analytical determination, there are many factors that should be taken into consideration as they affect the performance of the electrode towards its respective ion. Some of these factors are: composition of the membranes and the amount of ion-pairs, the plasticizer, soaking time and operational conditions such as temperature, pH and the presence of interferents. 3.2. Effect of the ion-pair complex Ion-pairs should have good solubility in the membrane matrix and sufficient lipophilicity to prevent leaching from the membrane into the sample solution [34]. In addition, the amount of ion-pair should be sufficient to make reasonable ionic exchange at the gel layer-test solution interface which is responsible for the membrane potential [35]. The ion-pairs of KT-PT, KT-PM and KT-TPB were prepared and then electrodes containing some or no ion-pair were made and their emf were measured at various concentrations of the KTCl. The electrode without the modifier (ion-pair) showed poor sensitivity to ketamine cations. However, in the presence of the ion-pair complexes the sensors displayed remarkable selectivity for KT cations. Electrodes with variable compositions ranging from 0.1% to 1.0% were tested. It was noted that the best response was spotted at 0.5% KT-PM in their PVC electrodes. However, the response deteriorated by electrodes containing more than the above compositions. That is likely due to inhomogeneity and possible saturation of the membranes [36]. These results are compiled in Table 1. 3.3. Membrane solvent or plasticizer effect The membrane solvent reduces the viscosity and ensures a relatively high mobility of the membrane constituents. Depending on its polarity and dielectric constant, it can influence the ion-pair characteristics of the membrane and, as a consequence the selectivity, detection limit, selectivity and sensitivity of the electrode [37,38]. To spot a suitable plasticizer for constructing this electrode, we used four plasticizers, with a range of characteristics, namely: the values of dielectric constants (which is a measure of the molecular polarity), lipophilicity and molecular weight respectively are in parentheses, for DOP (εr = 5.1, PTLC = 7.0, M. wt = 391), DBP (εr = 6.4, PTLC = 4.5, M. wt. = 278), DOS (εr = 4.2, PTLC = 10.1, M. wt = 426) and TEPh (εr = 4.8, PTLC = 10.2, M. wt = 435) and the results obtained are shown in Fig. 2 and Table 1. It seems that DBP, with relatively moderate viscosity, lipophilicity, molecular

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Table 1 Composition and slope of calibration curves for proposed electrode. Composition (%) Ion-exchanger 123456789101112-

– 0.1 (KT-PM) 0.3 (KT-PM) 0.5 (KT-PM)a 1.0 (KT-PM) 0.5 (KT-PM) 0.5 (KT-PM)a 0.5 (KT-PM) 0.5 (KT-PM) 0.5 (KT-PM) 0.5 (KT-TPB) 0.5 (KT-PT)

Plasticizer

A%

Slope

Concentration range

Detection limit

Response time (s)

0.20 0.20 0.20 0.20 0.20

40.0 ± 0.3 45.7 ± 0.6 50.4 ± 0.8 56.6 ± 0.3 48.2 ± 0.5 51.8 ± 0.5 56.6 ± 0.3 53.7 ± 1.2 60.0 ± 0.9 48.7 ± 0.5 54.8 ± 0.9 49.0 ± 0.4

3.8 × 10−5–8.0 × 10−2 7.4 × 10−6–1.0 × 10−2 6.5 × 10−6–1.0 × 10−2 1.5 × 10−6–1.0 × 10−2 6.0 × 10−6–1.0 × 10−2 5.0 × 10−6–1.0 × 10−2 1.5 × 10−6–1.0 × 10−2 6.3 × 10−6–1.0 × 10−2 3.0 × 10−5–1.0 × 10−2 9.0 × 10−6–1.0 × 10−2 9.0 × 10−6–1.0 × 10−2 8.3 × 10−6–1.0 × 10−2

1.1 × 10−5 5.2 × 10−6 3.0 × 10−6 1.2 × 10−7 3.9 × 10−6 1.7 × 10−6 1.2 × 10−7 5.0 × 10−6 1.8 × 10−5 7.8 × 10−6 6.4 × 10−6 5.2 × 10−6

25 9 11 7 15 12 7 12 10 10 13 15

PVC 51.6 50.8 50.7 51.0 49.5 51.0 51.0 51.0 51.0 51.0 51.0 51.0

48.2 48.9 48.8 48.3 49.3 48.5 48.3 48.3 48.3 48.3 48.3 48.3

DBP DBP DBP DBP DBP DBP DBP TEPh DOS DOP DBP DBP

0.20 0.20 0.20 0.20 0.20 0.20

A: sodium tetraphenylborate. a Selected composition.

weight and low dielectric constant, produced the best results. This is due to the ability of DBP to extract ketamine ions from the aqueous solution to the organic paste phase.

1.5 × 10−6–1.0 × 10−2 M, 2.1 × 10−6–1.0 × 10−2 M and 2.7 × 10−6– 1.0 × 10−2 M) and the most appropriate inner filling solution was 10−2 M KCl + 10−3 M KTCl.

3.4. Effect of internal reference solution

3.5. The influence of anionic additives

The key to the improvements of detection limit has been the reduction of zero current ion flux effects that enhance the primary ion activities in the sensed sample layer near the membrane surface. This has been achieved by careful adjustment of the composition of the inner solution by reducing ion fluxes in the membrane and the thickness of the aqueous diffusion layer [39]. Primary ions contaminating the sample in the sensed layer originate either from the membrane or from the internal solution [39]. To investigate the effects of the inner filling solutions on the ketamine ion-selective electrode response, the electrodes prepared were filled with different inner filling solutions (10−2 M KCl + 10−2 M KTCl, 10−2 M KCl + 10−3 M KTCl, 10−2 M KCl + 10−4 M KTCl and 10−2 M KCl + 10−5 M KTCl) and calibration graphics were plotted for each case. The concentration range was (3.2 × 10−6–1.0 × 10−2 M,

Additives such as lipophilic anions (Na-TPB) reduce ohmic resistance and improve response behavior and selectivity in cationselective electrodes. In addition, they enhance the selectivity of the membrane electrode in cases where the extraction capability of the ion-pair is poor. Furthermore, the lipophilic additive may catalyze the exchange kinetics at the sample-electrode interface [40,41]. Comparison of the data (for electrodes 6 and 7) revealed that the sensitivity of the sensor increased, slope of the calibration curve increased from 51.8 ± 0.5 to 56.6 ± 0.3 mV/decade and the detection limits decreased from 1.5 × 10−6 to 1.2 × 10−7 M with the addition of a trace of Na-TPB (about 0.2 wt.%) as shown in Fig. 3. The effect of a lipophilic additive can be explained. Liquid membranes for ionophore-based ISEs contain ionophores and ion pairs (ionic sites). Coextraction of ionophore/primary ion complexes with counter ions occurs but making no charge separation at the interface. Addition of a lipophilic additive produces an oriented layer for ionophore/analyte ion complexes developed at the organic/ aqueous interface in the organic side of the interface leaving their hydrophilic counter ions in the aqueous counterpart. The extent of this charge separation is dependent on the activity (concentration) of the respective analyte ions and is measurable as changes in the membrane boundary potential. The ionic sites reject counter ions from being coextracted into the organic phase hence generation of analyte-ion activity (concentration)-dependent membrane potential changes [42,43]. Among the different compositions studied, the membrane incorporating 51.0% PVC, 48.3% (DBP), 0.5% ion-pair and 0.20% Na-TPB exhibits the best response characteristics with a slope of 56.6 ± 0.3 mV/decade and detection limit of 1.2 × 10− 7 M over wide concentration range 1.5 × 10−6–1.0 × 10−2 M of ketamine ions as given in Table 1. Therefore, this composition was used to study various operation parameters of the electrode. The electrochemical performance characteristics of the electrode was systematically evaluated in accordance with the procedures of the IUPAC recommendations [44]. 3.6. Effect of temperature

Fig. 2. Effect of various plasticizers on the measured potential.

At 25 °C the slope was 56.6 mV/decade and at 55 °C was 55.8 ± 0.1 mV/decade for ketamine ion over a wide concentration range from 1.5 × 10−6–1.0 × 10−2. This indicates high thermal stability of the electrodes within the investigated temperature range and shows insignificant deviation from the theoretical Nernst behavior.

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The performance characteristics of the investigated electrode were studied as a function of soaking time. The effect of soaking on the performance of the electrode was studied by soaking each electrode in 1.0 × 10−3 M solution of KTCl for variable intervals starting from 15 min reaching to 27 days. The slopes of the electrode were observed to show gradual decrease after 22 days (from 56.6 to 52.5 mV/decade). Loss of the plasticizer, ion-pair from the polymeric film, as a result of leaching into the sample, is the primary reason for the limited lifetime of sensor [46]. 3.8. Effect of pH It can be seen from Fig. 5 that the variation in potential due to pH change is considered acceptable in the pH range 3.0–6.8. However, there is an observed drift at pH values lower than 3.0 which may be due to H+ interference. On the other hand, the potential decreases gradually at pH values higher than 6.8. The decrease may be attributed to hydroxide ions that react with ketamine leading to formation of free drug in the test solution, neutral species, which could not be extracted into the membrane. 3.9. Effect of interfering ions Fig. 3. The calibration curve and the detection limit value with and without Na-TPB for KT-PM electrode.

3.7. Dynamic response time, repeatability and soaking time of the electrode

One of the most important characteristics of an ISE is its relative response to other ions present in solution. This is expressed in terms of selectivity coefficients. In analytical applications, the selectivity for the analyte must be as high as possible, i.e. the selectivity for foreign substances must be very small, so that the electrodes exhibit a Nernstian dependence on the primary ion over a wide concentration range. The response of the electrode towards different substances and ionic species such as inorganic and organic cations as well as different excipients which may be present in pharmaceutical preparations was tested.

Other crucial parameter when evaluating the performances of ISEs is their response time. The response time of the electrode is defined as the time between addition of the analyte to the sample solution and the time when a limiting potential has been reached [44,45]. In this work, the response time of the electrode was measured by varying the KT+ concentration over the range from 1.0 × 10− 5 to 1.0 × 10− 2. As shown in Fig. 4, the electrode reached equilibrium in about 7 s. The potential reading stays constant, to within ±1 mV, for at least 6 min. The repeatability of the potential reading of the electrode was examined by subsequent measurements of 1.0 × 10−4 M KT solution immediately after measuring the first set of solutions at 1.0 × 10−3 M KT. The standard deviation of measuring emf for 5 replicate measurements was found to be 1.148 for 1.0 × 10−4 M solution and 0.732 for 1.0 × 10−3 M solution. This indicates excellent repeatability of the potential response of the electrode.

in Table 2. These values give no significant interference in the process of the sensor due to the differences in their mobilities and permeabilities as compared with KT+ [47]. The selectivity mechanism is mainly based on the stereospecificity and electrostatic environment and is dependent on how much fitting is present between the locations of the lipophilicity sites in the two competing species on the bathing solution side and those present in the receptor of the ion exchanger. The inorganic cations do not interfere because of differences in the ionic size, the mobility and the permeability. In addition, the smaller is the energy of hydration of the cation, the greater is the response of the membrane. Overall, these notes are in line with the greater similarity in

Fig. 4. Dynamic responses of the proposed electrode obtained by successive increase of ketamine hydrochloride.

Fig. 5. Influence of pH on the response of the developed sensor.

The resulting values of selectivity coefficients− log K Pot are collected KT; J Zþ

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Table 2 Selectivity coefficient values for ketamine sensor.

Table 3 Analysis of ketamine in real samples using different methods.

Interfering ions

MPM

SSM

Na+ K+ Ag+ Li+ Cd++ Ca++ Ni++ Co++ Cu++ Pb++ Zn++ Cr+++ Ampicillin Rocephin Gentamycin Lasix Hydrocortisone Diclofenac Glucose Galactose Fructose Sucrose

1.13 × 10−5 4.16 × 10−5 6.42 × 10−4 1.81 × 10−5 5.62 × 10−4 9.64 × 10−5 2.86 × 10−4 1.47 × 10−5 8.85 × 10−4 1.14 × 10−4 1.78 × 10−4 6.61 × 10−5 4.51 × 10−4 1.43 × 10−3 2.65 × 10−4 1.96 × 10−4 8.02 × 10−4 5.17 × 10−4 – – – –

8.73 × 10−5 7.05 × 10−5 5.24 × 10−4 3.15 × 10−4 3.58 × 10−4 1.97 × 10−5 4.32 × 10−4 2.77 × 10−4 6.28 × 10−5 2.42 × 10−4 2.46 × 10−4 4.23 × 10−5 1.79 × 10−5 3.83 × 10−4 1.47 × 10−3 4.75 × 10−4 6.38 × 10−5 2.30 × 10−4 7.15 × 10−4 5.48 × 10−5 1.42 × 10−4 8.60 × 10−5

the composition of the membrane to that of ketamine ion as compared to those of the other ions which entail better compatibility and enhanced response [48]. 3.10. Applications Several methods are applied for quantitative analysis using the proposed electrode. These methods comprise: (i) the calibration curve method (direct potentiometry), (ii) the standard addition method, which is frequently applied in using ISE, and (iii) potentiometric titration involving the use of counter ion as titrant. 3.10.1. The calibration curve method A calibration curve is a general method for determination of the concentration of a substance in unknown sample by comparing the response of the unknown to those of a set of standard samples of known concentration. Pharmaceutical formulation (ampules) KTCl was determined by the calibration curve method. The results, compiled in Table 3, have relative standard deviation (RSD) of (97.25– 102.00)%(0.14–1.18) and an average recovery of (97.25–101.20)%. The accuracy and precision of these findings indicate viability of these electrodes in KTCl determination.

Samples

Ampule C

S

Urine C

S

M

X%

RSDa%

F-value

t-Value

Taken

Found

1.00 × 10−5 5.50 × 10−5 2.00 × 10−4 1.00 × 10−5 7.55 × 10−5 5.00 × 10−4

9.95 × 10−6 5.57 × 10−5 1.95 × 10−4 9.88 × 10−5 7.35 × 10−5 4.92 × 10−4

99.50 101.2 97.50 98.80 97.35 98.40

1.06 0.89 1.75 1.18 0.73 0.14

2.36 2.18 2.54 3.21 2.55 1.99

3.01 1.85 0.29 3.14 2.89 1.75

1.00 × 10−5 8.00 × 10−5 2.00 × 10−4 1.00 × 10−5 1.00 × 10−4 5.00 × 10−4

9.85 × 10−6 7.78 × 10−5 1.93 × 10−4 1.02 × 10−5 1.01 × 10−4 4.87 × 10−4

98.50 97.25 98.75 102.0 101.0 97.40

1.08 1.13 0.24 0.58 0.89 0.42

2.35 2.45 2.19 1.54 1.98 1.43

0.71 1.53 1.86 2.36 2.96 2.35

S: standard additions method, C: calibration curve method, X: recovery, RSD: relative standard deviation. The critical value of F = 9.28 and the critical value of t = 3.707. a The number of replicate measurements = 5.

3.10.4. Recovery and determination of ketamine ions in urine Clinical pharmacological studies indicate that ketamine is metabolized in the liver by hydrolysis to norketamine followed by conjugation with glucuronate and then excreted renally with an elimination half-life of 2–3 h in adults. After intravenous administration, ketamine shows a bi- or tri-exponential pattern of elimination. The alpha phase lasts about 45 min with a half-life of 10 to 15 min. This first phase, which represents the anesthetic action of ketamine, is terminated by redistribution from the CNS to peripheral tissues and hepatic biotransformation to an active metabolite. The beta phase half-life is about 2.5 h. About 90% of ketamine is excreted in the urine and approximately 5% is recovered in the feces [49, 50]. Recovery experiments were conducted by spiking urine samples with appropriate amounts of ketamine hydrochloride, and determined by the electrode using the standard addition and the calibration curve method. The results, shown in Table 3 indicate recoveries and relative standard deviation values range between (97.25–102.00) and (0.1– 1.75). It is noted that the results are accurate and reproducible. Thus the sensor can be employed for quantification of ketamine ion in urine samples.

3.10.2. The standard addition method KTCl in ampules was determined by the standard addition method. The results, shown in Table 3, indicate that recovery range from (97.25–101.20)% and small relative standard deviation ranging from (0.14–1.18)% KTCl ampules. These values reflected high accuracy and precision of the studied electrodes as sensors for the drug. 3.10.3. The potentiometric titration method The potentiometric titration technique usually has the advantage of high accuracy and precision, but with increased consumption of titrants. A further advantage is that the potential break at the equivalent point is well defined. The potentiometric titration of KTCl is based on the decrease of the drug cation concentration by precipitation with tetraphenylborate (TPB−) anion. The feasibility of such titration depends on the degree of completeness of the reaction. As is obvious from Fig. 6, the amount of ketamine can be accurately determined from the end point of the titration curve.

Fig. 6. Potentiometric titration of 10.0 mL of 1.0 × 10−2 M KTCl with 1.0 × 10−2 M Na-TPB.

H.M. Abu Shawish et al. / Materials Science and Engineering C 49 (2015) 445–451

3.10.5. Statistical treatment of results The results of applying the above methods are compared with the values obtained from the official method [51]. F test was used for comparing the precisions of the two methods and t-test for comparing the accuracy. The calculated F and t-tests in Table 3 were less than the critical (tabulated) ones. Thus, there is no significant difference between the precisions or the accuracies of the methods at 95% confidence levels. 4. Conclusions This study described the electrodes fabricated to measure ketamine ion and stressed the best electrode. It comprises ketaminephosphomolybdate (KT-PM) as ion-exchanger combined with the lipophilic anionic additive (Na-TPB) dissolved in dibutyl phthalate (DBP) as a plasticizer. The present electrode has notable features as it provides measurements of the potential with a near-Nernstian slope of 56.6 ± 0.3 mV/decade over the concentration range of 1.5 × 10−6– 1.0 × 10−2 M in a short response time (7 s). Attractively, it has a low detection limit of 1.2 × 10−7 M and its life-span is 22 days. The electrode showed attractive performance when tested in various samples and urine with excellent repeatability and sensitivity. As an ISE, the proposed electrode offers the advantages of simplicity, accuracy, automation feasibility and applicability to various sample solutions. Acknowledgments The authors would like to thank Dr Ashraf abu Mhady and Dr Amal Zendah (General Administration of Pharmacy, Ministry of Health, Gaza, Palestine) for the encouragement, support and providing facilities for research. References [1] A. Bairros, R. Lanaro, R.M. Almeida, R. Almeida, M. Yonamine, Forensic Sci. Int. 243 (2014) 47–54. [2] S.P. Cheng, Y.C. Fu, C.H. Lee, C. Liu, C.S. Chien, J. Chromatogr. B 852 (2007) 443–449. [3] K.M. Kim, J.S. Lee, S.K. Choi, M.A. Lim, H.S. Chung, Forensic Sci. Int. 174 (2008) 197–202. [4] Y. Chen, Y. Yang, Y. Tu, Sensors Actuators B 183 (2013) 150–156. [5] H.P. Jen, L.H.Y.C. Tsai, H.L. Su, Y.Z. Hsieh, J. Chromatogr. A 1111 (2006) 159–165. [6] J. Xiong, J. Chen, M. He, B. Hu, Talanta 82 (2010) 969–975. [7] H.R. Lin, A.C. Lua, Tzu Chi Med. J. 17 (2005) 213–217. [8] F. Niedorf, H.H. Bohr, M. Kietzmann, J. Chromatogr. B 791 (2003) 421–426. [9] J.Y. Kim, S.H. Shin, M.K. Ln, Forensic Sci. Int. 194 (2010) 108–114. [10] C.H. Wu, M.H. Huang, S.M. Wang, C.C. Lin, R.H. Liu, J. Chromatogr. A 1157 (2007) 336–351. [11] K. Lian, P. Zhang, L. Niu, D. Bi, S. Liu, L. Jiang, W. Kang, J. Chromatogr. A 16 (2012) 104–109.

451

[12] M. Sergi, D. Compagnone, R. Curini, G. Ascenzo, M.D. Carlo, S. Napoletano, R. Risoluti, Anal. Chim. Acta. 675 (2010) 132–137. [13] T. Legrand, T. Roy, S. Monchaud, C. Grondin, M. Duval, E. Jacqz-Aigrain, J. Pharm. Biomed. Anal. 48 (2008) 171–176. [14] L. Zhang, Z. Wang, H. Li, Y. Liu, M. Zhao, Y. Jiang, W. Zhao, J. Chromatogr. B 955–956 (2014) 10–19. [15] M.K. Huang, C. Liu, J.H. Li, S.D. Huang, J. Chromatogr. B 820 (2005) 165–173. [16] C.Y. Chen, M.R. Lee, F.C. Cheng, G.J. Wu, Talanta 72 (2007) 1217–1222. [17] M.C. Parkin, S.C. Turfus, N.W. Smith, J.M. Halket, R.A. Braithwaite, S.P. Elliott, M.D. Osselton, D.A. Cowan, A.T. Kicman, J. Chromatogr. B876 (2008) 137–142. [18] N. Harun, R.A. Anderson, E.I. Miller, J. Anal. Toxicol. 33 (2009) 310–321. [19] H.R. Lin, A.C. Lua, Rapid Commun. Mass Spectrom. 20 (2006) 1724–1730. [20] T. Nema, E.C. Chan, P.C. Ho, J. Sep. Sci. 34 (2011) 1041–1046. [21] S.D. Brown, D.J. Rhodes, B.J. Pritchard, Forensic Sci. Int. 171 (2007) 142–150. [22] Z. Chenggong, Z. Qian, C. Bo, M. Ming, Chin. J. Chromatogr. 25 (2007) 641–645. [23] N. Alizadeh, R. Mehdipour, J. Pharm. Biomed. Anal. 30 (2002) 725–731. [24] J. Lenik, Mater. Sci. Eng. C 45 (2014) 109–116. [25] H.M. Abu Shawish, S.M. Saadeh, A.R. Al-Dalou, N. Abu Ghalwa, A.A. Abou Assi, Mater. Sci. Eng. C 31 (2011) 300–306. [26] M. Gaber, H.M. Abu Shawish, A.M. Khedr, K.I. Abed-Almonem, Mater. Sci. Eng. C 32 (2012) 2299–2305. [27] E.W. Mrof, M. Badertscher, T. Zwicki, F.N. De Rooij, E. Pretsch, J. Phys. Chem. B 103 (1999) 11346–11356. [28] U. Fiedler, Anal. Chim. Acta. 89 (1977) 111–118. [29] J. Moret, F.T.C. Moreira, S.A.A. Almeida, M.G.F. Sales, Mater. Sci. Eng. C 43 (2014) 481–487. [30] E. Bakker, P. Bühlmann, E. Pretsch, Chem. Rev. 97 (1997) 3083–3132. [31] M.M. Hosny, Taiwan Pharm. J. 59 (2007) 25–30. [32] H. Ibrahim, Y.M. Issa, H.M. Abu-Shawish, J. Pharm. Biomed. Anal. 36 (2005) 1053–1061. [33] Y. Umezawa, P. Buhlmann, K. Umezawa, K. Tohda, Pure Appl. Chem. 72 (2000) 1851–2082. [34] V.S. Bhat, V.S. Ijeri, A.K. Srivastava, Sens. Actuators B99 (2004) 98–105. [35] A.F. Shoukry, Y.M. Issa, R.M. El-Nashar, Microchim. J. 69 (2001) 189–197. [36] M. Shamsipur, M. Hosseini, K. Alizadeh, M.M. Eskandari, H. Sharghi, M.F. Mousavi, M.R. Ganjali, Anal. Chim. Acta. 486 (2003) 93–99. [37] A. Ceresa,(Doctoral dissertation) Swiss Federal Institute of Technology, Zurich (2001). [38] A.R. Fakhari, T.A. Raji, H. Naeimi, Sens. Actuators B104 (2005) 317–323. [39] J. Sutter, A. Radu, S. Peper, E. Bakker, E. Pretsch, Anal. Chim. Acta. 523 (2004) 53–59. [40] M. Shamsipur, M. Yousefi, M. Hosseini, M.R. Ganjali, Anal. Chem. 74 (2002) 5538–5543. [41] U. Schaller, E. Bakker, U.E. Spichiger, E. Pretsch, Anal. Chem. 66 (1994) 391–398. [42] R.E. Gyurcsanyi, E. Lindner, Anal. Chem. 74 (2002) 4060–4068. [43] Y. Tani, Y. Umezawa, Sens. Lett. 3 (2005) 99–107. [44] P.R. Buck, E. Lindner, Pure Appl. Chem. 66 (1994) 2527–2536. [45] I. Jebali, J.E. Belgaied, Mater. Sci. Eng. C 37 (2014) 90–98. [46] Z. Kormosh, I. Hunka, Y. Bazel, O. Matviychuk, Mater. Sci. Eng. C 30 (2010) 997–1002. [47] M.A. Mazlum, H.E.A.A. Naeimi, A. Dastanpour, A. Shamlli, Sens. Actuators B 96 (2003) 441–445. [48] N.T. Abdel-Ghani, Y.M. Issa, H.M. Ahmed, Sci. Pharm. 74 (2006) 121–135. [49] J.A. Clements, W.S. Nimmo, Br. J. Anaesth. 53 (1981) 27–30. [50] United States Pharmacopeia Dispensing Information18th Edition, 1998. 1775–1777. [51] British Pharmacopia, Vol 1 & II, (M.G. Lee), MHRA, Market Towers, 1 Nine Elms Lane, London SW8 5NQ, (2009).

A new approach for decreasing the detection limit for a ketamine(I) ion-selective electrode.

Our endeavors of lowering the detection limit for a ketamine(I) ion-selective electrode were described. The paper stresses the electrode which showed ...
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