Oxidation and reduction of omeprazole on boron-doped diamond electrode: Mechanistic, kinetic and sensing performance studies

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Oxidation and reduction of omeprazole on boron-doped diamond electrode: Mechanistic, kinetic and sensing performance studies Zuzana Chomisteková a , Eva Culková a , Renata Bellová a , Danica Melicherˇcíková a , Jaroslav Durdiak a , Jaroslav Timko b , Miroslav Rievaj a , Peter Tomˇcík a,∗ a Department of Chemistry and Physics, Faculty of Education, Catholic University in Ruˇzomberok, Hrabovská cesta 1, SK-034 01 Ruˇzomberok, Slovak Republic b Department of Laboratory Methods in Health Care, Faculty of Health Care, Catholic University in Ruˇzomberok, Námestie A. Hlinku 48, SK-034 01 Ruˇzomberok, Slovak Republic

a r t i c l e

i n f o

Article history: Received 1 June 2016 Received in revised form 30 September 2016 Accepted 5 October 2016 Available online xxx Keywords: Omeprazole Boron-doped diamond electrode Voltammetry Urine Pharmaceuticals

a b s t r a c t Voltammetric behavior of omeprazole on chemically unmodified boron-doped diamond electrode was investigated. Omeprazole is possible to oxidize and reduce in various supporting electrolytes. Both processes are strongly dependent on pH value of the solution. Well defined oxidation and reduction signal of omeprazole was observed at high and low pH values of supporting electrolyte. Kinetics of charge transfer in the pH range from 3 to 10 in various supporting electrolytes was studied and characterized by the estimation of formal potentials (+1.07 to +0.89 V for oxidation and −0.95 to −1.18 V for omeprazole reduction), charge transfer coefficients (0.52–0.33 for oxidation and 0.19–0.17 for reduction) together with standard heterogeneous rate constants. The analytical performance was studied with linear sweep voltammetry, square-wave voltammetry and differential pulse voltammetry. The lowest detection limit of 9.1 × 10−8 mol L−1 for oxidation of omeprazole was achieved by SWV technique. The proposed simple, sensitive and cheap method was validated and applied for pharmaceutical formulations and human urine as real samples. © 2016 Elsevier B.V. All rights reserved.

1. Introduction Omeprazole (OMZ), 5-methoxy-2-[[(4-methoxy-3,5-dimethyl2-pyridinyl)methyl]sulphinyl]-1H-benzimidazole (Scheme 1A), belongs to group of drugs called proton pump inhibitors (PPI). OMZ enters into the gastric parietal cell via the blood system and accumulates in the secretory canaliculi where it is changed to sulfenamide [1]. This active form is irreversibly bound on the H+ /K+ -ATPase enzyme system to inhibit gastric acid production. Omeprazole is used for the treatment of gastroesophageal reflux disease (GERD), ulcers, erosive esophagitis and Zollinger-Ellison syndrome. Omeprazole may also be applied with antibiotics to treat gastric ulcer caused by infection with helicobacter pylori [2,3]. Pharmaceutical formulations of omeprazole are available as tablets and capsules (containing pure omeprazole or its magnesium salt) or a powder (sodium salt of omeprazole) for intravenous applications. The most of OMZ pharmaceutical formulations for oral use

∗ corresponding author. E-mail address: [email protected] (P. Tomˇcík).

are enteric-coated, due to rapid degradation of the tablet or capsule only in the acidic media of the stomach [4]. For the determination of OMZ in pharmaceutical and biological samples several analytical methods have been developed. The most popular, but rather expensive are separation techniques, e.g. liquid chromatography with tandem mass spectrometry (LC–MS/MS) with a detection limit of 2.3 × 10−9 mol L−1 [5]. Similar sensitivity shows hydrophilic interaction liquid chromatography method hyphenated with tandem mass spectrometry (HI-LC–MS/MS) where LOD of 2.2 × 10−9 mol L−1 was achieved [6] as well as HPLC coupled with UV (LOD = 7.2 × 10−9 mol L−1 ) or coulometric (LOD = 1.7 × 10−8 mol L−1 ) detection [7]. The less sensitive are thin layer chromatography (TLC) with detection limit of 1.4 × 10−5 mol L−1 [8], supercritical fluid chromatography (SFC), micellar electrokinetic capillary chromatography (MEKC) with LOD of 1.1 × 10−7 mol L−1 and capillary electrophoresis (CE) where LOD of 9.0 × 10−7 mol L−1 was reached [9]. UV spectrophotometry has been applied into OMZ analysis in borate buffer solution with pH value of 10 in the concentration range 5.8 × 10−7 –1.1 × 10−4 mol L−1 [10]. Sastry et al. have been described four spectrophotometric simple and sensitive techniques based on the generation of colored compounds forming

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Scheme 1. A: Chemical structure of OMZ. B: Oxidation of OMZ. C: Reduction of OMZ.

from OMZ and 3-methyl-2-benzothiazolinone hydrazone following by oxidation with ferric chloride (LOD = 2.1 × 10−7 mol L−1 ) or m-aminophenol subsequent to oxidation with chloramineT (LOD = 3 × 10−7 mol L−1 ) as well as Folin-Ciocalteu reagent in the sodium carbonate (LOD = 1.1 × 10−7 mol L−1 ). The last technique is based on the oxidation of OMZ with an excess of N-bromosuccinimide (NBS) and determination of the consumed NBS with a decay of color intensity of Celestine blue (LOD = 5.8 × 10−8 mol L−1 ) [11]. The development of new, simple, fast and cheap techniques for the determination of drugs both in pharmaceutical and biological samples is important in the contemporary electroanalytical chemistry, because electroanalytical methods have the above mentioned attributes. They are highly sensitive and selective allowing direct measurement of samples with very little or no sample pretreatment. As observed Brett et al. [12] OMZ is anodically and cathodically electroactive, therefore various electroanalytical tech-

niques were developed for its detection. The AC polarographic method on DME has been used for determination of OMZ in human plasma. This technique has linear dynamic concentration range from 6 × 10−7 to 3 × 10−5 mol L−1 and rather low detection limit of 2.9 × 10−8 mol L−1 in Britton-Robinson buffer solution with pH value of 9.6 [13]. The adsorptive stripping voltammetric method has been applied for study of the electrochemical behavior of OMZ in 0.1 mol L−1 phosphate buffer solution with pH 7.0 on edge-plane pyrolytic graphite electrode. The optimization of experimental parameters shows a good linearity between peak height and analyte concentration in the concentration range from 1 × 10−8 to 4 × 10−6 mol L−1 with a detection limit of 3 × 10−9 mol L−1 [14]. Mercapto-mesoporous carbon modified carbon paste electrode (LOD = 4 × 10−11 mol L−1 ) [15] was also used for the detection of OMZ as well as, glassy carbon electrode modified with multiwalled carbon nanotubes (MWCNT), polyaniline (PANI) (LOD = 1.4 × 10−4 mol L−1 ) [16] together with glassy carbon

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electrode modified with electrodeposited nickel oxide nanoparticles (NiOxNPs) (LOD = 4 × 10−7 mol L−1 ) [17]. The main aim of this work was to develop a new technique which does not include time consuming preparation and chemical modification of sensor to avoid significant complications in the analytical process. We present here boron-doped diamond film electrode placed in polyetherether ketone tube [18,19] as very simple, sensitive and chemically unmodified sensor [20] for fast detection of OMZ in pharmaceutical and biological samples. 2. Experimental All electrochemical experiments were carried out in three electrode arrangement in a glass electrochemical cell maintained at 25.0 ± 0.5 ◦ C. Boron-doped diamond film electrode with polycrystalline structure inserted in polyetherether ketone (PEEK) tube with a diameter of 3 mm, 0.5 mm thickness, resistivity of 0.75 × 10−3  m, boron doping level of 1000 ppm (or 1020 boron atoms cm−3 ) (declared by Windsor Scientific Ltd., UK) was used as working electrode. Ag/AgCl (3 mol L−1 KCl) electrode served as reference and platinum macroelectrode with area of 1 cm2 as counter electrode. Voltammetric measurements were realized with Autolab PGSTAT 302N (Metrohm Autolab BV, The Netherlands) controlled by NOVA 1.6 electrochemical software. Before each measurement the surface of boron-doped diamond electrode was cleaned sonically (Elmasonic P, Elma Hans Schmidbauer GmbH & Co. KG, Germany), following aqueous suspension of alumina and rinsed with distilled water. Then electrochemical activation with constant potential of +5.0 V vs. Ag/AgCl for 60 s before each scan was applied. All chemicals were of p. a. purity. Deionized water (EUROWATER, Bratislava) was used for the preparation of all solutions. H3 PO4 (0.2 mol L−1 , LACHEMA, Brno), NaH2 PO4 ·H2 O (pH = 4.6; 0.2 mol L−1 , LACHEMA, Brno), phosphate buffer solution (PBS) with pH value of 7 (0.1 mol L−1 , prepared from 0.2 mol L−1 Na2 HPO4 ·12H2 O – LACHEMA, Brno and 0.2 mol L−1 NaH2 PO4 ·H2 O – LACHEMA, Brno), Na2 HPO4 ·12H2 O with pH of 9.8 (0.2 mol L−1 , LACHEMA, Brno), NaOH (0.2 mol L−1 , CENTRALCHEM, Bratislava) and Na2 B4 O7 .10H2 O with pH of 10.0 (0.1 mol L−1 , LACHEMA, Spolana n.p. Neratovice) served as supporting electrolytes. A standard stock solution of 5.8 × 10−3 mol L−1 omeprazole was prepared in 0.2 mol L−1 sodium hydroxide solution and further solutions with various concentrations were prepared by dilution from a stock solution. 25 mL of supporting electrolyte was pipetted into electrochemical cell and following various additions of OMZ solution. The solutions were bubbled with pure nitrogen for 10 min before each voltammetric measurement. Human urine without omeprazole was spiked with known concentration of OMZ and standard addition calibration plot method was used for its quantification. As for real samples analysis the content of one capsule of Helicid® (Zentiva, CZE) and Omeprazol® (Sandoz, SLO) was emptied, weighted and powdered following the dilution in 0.2 mol L−1 NaOH under intensive stirring with magnetic stirrer. After filtration the filtrate was transferred into 50 mL volumetric flask. From this solution 0.5 mL was pipetted into electrochemical cell and filled with supporting electrolyte for volume of 25 mL. 2.5 mL of fresh urine was diluted to 25 mL with supporting electrolyte and directly analyzed.

Fig. 1. Cyclic voltammograms of 1.2 × 10−3 mol L−1 omeprazole solution in 0.1 mol L−1 PBS (pH = 3) (solid line) and PBS (pH = 3) (dashed line) on BDD electrode at scan rate of 50 mV s−1 .

peaks for omeprazole oxidation and one for reduction was found in PBS (pH = 3). These processes in the case of organic molecules are connected with protons transfer; therefore voltammetric signals of oxidation and reduction are dependent on pH value. Using linear sweep voltammetry it was observed no shift of the anodic potentials for OMZ oxidation, but the second anodic peak disappeared in alkaline media whereas the magnitude of first peak was significantly increased. The highest signal for 0.1 mol L−1 sodium tetraborate solution was obtained. It is interesting that in the case of pH = 7 four times higher signal was reached for 0.1 mol L−1 KCl in comparison with 0.1 mol L−1 PBS solution with the same pH. Based on these results it can be deduced that interaction between OMZ molecule and phosphate ions may influence the process. In Fig. 2A baseline corrected linear sweep voltammograms for omeprazole reduction at various pH values are shown. From this depencence, it is evident that with growing of alkality cathodic potential of OMZ shifts towards to more negative values. It was found that signal is substantially higher at lower values of pH than in neutral solutions and reduction peak disappeared in weakly alkaline solutions. No signal was observed for 0.1 mol L−1 KCl at pH of 7 whereas in 0.1 mol L−1 PBS (pH = 7) small reduction peak was obtained. From Ep vs. pH dependence ratio of electrons and protons was calculated on glassy carbon electrode [12]. It was observed that one electron and one proton taking part in first oxidation step and two electrons and two protons in the second oxidation step (Scheme 1B). We reached practically similar results, however with low precision due to relatively slow charge transfer of omeprazole on BDD electrode in all cases. Dependence of reduction peak potential on pH value (Fig. 2B) was found to be linear with parameters: A = −99.6 × 10−2 V, B = −38.5 × 10−3 V, sA = 9.91 × 10−3 V, sB = 1.91 × 10−3 V, R2 = 0.990. The slope of this dependence is 2.3026nRT zF

3. Results and discussion

B=−

First, the voltammetric behavior of omeprazole on unmodified boron-doped diamond electrode was investigated by cyclic voltammetry at various pH values of supporting electrolytes based on mixture of H3 PO4 , NaH2 PO4 and Na2 HPO4 . Cyclic voltammograms are depicted in Fig. 1. As can be seen from this figure, two

where n is number of protons a z is number of electrons taking part in electrochemical reaction, the remaining symbols have usual physical sense. From above mentioned dependence for one electron 0.7 protons were calculated. As we mentioned above the quite large deviation from the value of 1.00 is caused by irreversibil-

(1)

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Fig. 2. A: Background corrected linear sweep voltammograms of reduction of 1.2 × 10−3 mol L−1 omeprazole solution measured at various pH values of 0.1 mol L−1 supporting electrolytes (phosphate buffer solution with pH value of 3, 4, 5, 6, 7). Scan rate was 25 mV s−1 . B: The dependence of reduction peak potential of 1.2 × 10−3 mol L−1 omeprazole solution at various pH values of 0.1 mol L−1 supporting electrolytes based on mixture of Na2 HPO4 , NaH2 PO4 and H3 PO4 . Scan rate was 25 mV s−1 . Background was subtracted.

ity of electrode process while for reversible systems substantially closer values may be reached using the equation (1). However, the reduction of omeprazole proceeds on sulfoxide group involving two-electrons and two-protons transfer as can be seen from the Scheme 1C or from ref. [13]. The difference in our results may be caused by higher noise therefore cathodic signal of OMZ is decreased with growing pH value. Then we measured the dependence of peak current magnitude on square root of scan rate for oxidation and reduction of omeprazole. Examples of dependencies are shown in Fig. 3. They were found to be linear in the range of 10–300 mV s−1 confirming that the oxidation and reduction of omeprazole on boron doped diamond electrode is controlled by diffusion and both processes are not connected with adsorption or another surface phenomenon. This is typical for boron doped diamond materials with low ability to be chemically modified by adsorption. Based on these studies it may be said that oxidation [12] and reduction [13] of omeprazole is typical reaction with a strong influence of hydrogen ions. Oxidation is decelerated with protons present in the solution (not adsorbed on the electrode) and the reduction is accelerated by protons as the reactant. Next, the kinetic consideration of the charge transfer for oxidation and reduction of omeprazole on boron-doped diamond electrode in various supporting electrolytes was performed. In Fig. 4 some dependencies of LSV peak potential on scan rate for both processes are presented. The peak potential grows practically linearly with the scan rate in the range of 10–300 mV s−1 , but for higher scan rates a slight curvature was observed. These dependencies were nonlinearly fitted and the fits were extrapolated to  = 0. Calculated potential for scan rate equal to zero is formal potential [21]. Obtained results are summarized in Table 1 and 2. As can be seen from these tables the formal potential for the oxidation and reduction of omeprazole depends on pH value of supporting electrolyte and it is from range of 1.07–0.89 V for oxidation and E0 ∈ < −0.95 V to −1.18V> for OMZ reduction. Formal potentials are slightly shifted to more negative values for both processes. Then, the charge transfer coefficients of oxidation and reduction of omeprazole on BDD electrode were calculated for each sup-

Table 1 Charge transfer characterization data for omeprazole oxidation on boron-doped diamond electrode for various supporting electrolytes with concentration of 0.1 mol L−1 . 

electrolyte

␣

SD␣

E0 [V]

SDE0 [V]

k0 [103 cm s−1 ]

A B C D E F G

0.52 0.46 0.45 0.33 0.33 0.37 0.47

0.02 0.01 0.01 0.03 0.03 0.02 0.03

1.068 1.034 0.922 0.967 0.970 0.968 0.891

0.006 0.007 0.019 0.011 0.009 0.003 0.006

1.21 0.56 0.26 0.38 1.06 1.48 0.85

A-PBS pH = 3, B-PBS pH = 5, C-PBS pH = 7, D-KCl pH = 7, E-PBS pH = 8, F-PBS pH = 9, G-borate buffer solution with pH = 10.

porting electrolyte according to the known equation based on the potential difference between peak potential Ep and the potential corresponding to half-height of peak E1/2 [22]: |Ep − E1/2 | =

47.7 mV at 25◦ C ˛z

(2)

Before calculation the voltammograms were IR corrected, because IR drop is significant for BDD surface causing a slight dependence of charge transfer coefficient on scan rate [23]. After correction the difference |Ep − E½ | was found to be constant and ␣ values are statistically the same for each supporting electrolyte in the range of scan rate from 10 to 300 mV s−1 . The results are also summarized in Table 1 showing that obtained values are from the range (0.52–0.33, z = 1) for oxidation of OMZ and in the range of 0.19–0.17, z = 2 for OMZ reduction (Table 2) indicating that the charge transfer is irreversible in both cases. Based on previous parameters the estimates of standard heterogeneous rate constants k◦ in scan rate range of 10–300 mV s−1 were also calculated. In these calculations the value of diffusion coefficient of omeprazole in phosphate water solutions D = 2.31 × 10−6 cm2 s−1 published by Brett [12] was used in this equation: RT Ep = E + ˛zF 0



D1/2 0.78 + ln 0 + ln k

 ˛zF 1/2  RT

(3)

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Fig. 3. Dependence of LSV peak current vs. v1/2 for 1.2 × 10−3 mol L−1 omeprazole solution in various supporting electrolytes (0.1 mol L−1 ) on BDD electrode with scan rates of 10, 25, 50, 100, 150, 300 mV s−1 . A-PBS pH = 3, B-PBS pH = 5, C-PBS pH = 7, D-KCl pH = 7, E-PBS pH = 3, F-PBS pH = 5, G- PBS pH = 7 (A-D for oxidation of OMZ and E-G for reduction of OMZ). Background was subtracted.

Table 2 Charge transfer characterization data for omeprazole reduction on boron-doped diamond electrode for various supporting electrolytes with concentration of 0.1 mol L−1 . 

electrolyte

␣

SD␣

E0 [V]

SDE0 [v]

k0 [104 cm s−1 ]

A B C

0.19 0.17 0.17

0.02 0.01 0.02

−0.950 −1.141 −1.181

0.019 0.005 0.008

1.18 1.82 1.11

A-PBS pH = 3, B-PBS pH = 5, C-PBS pH = 7.

Obtained k0 values for oxidation of omeprazole are of cm s−1 order. It is typical for slow charge transfers (Table 1). In the case of omeprazole reduction lower values of k0 were achieved depending on the pH value of measured solution (Table 2). In the next experiments we also investigated analytical performance of oxidation and reduction of omeprazole on boron-doped diamond electrode. In Fig. 5 A baseline corrected anodic linear sweep voltammograms in PBS (pH = 10) are presented for various concentrations of OMZ. As can be seen from this figure the response of BDD electrode is sensitive to additions of 10−3 –10−4

OMZ and linearly depends on its concentration in the range of 2.3 × 10−6 –1.4 × 10−5 mol L−1 (Fig. 5B). The linearity of calibration curve was verified by F-test and following parameters were calculated: intercept A = −1.49 × 10−8 A, sA = 1.1 × 10−9 A, slope B = 0.0228 A L mol−1 , sB = 5.7 × 10−4 A L mol−1 , R2 = 0.99. The detection limit calculated as 3snoise /B where snoise is standard deviation of noise calculated from background response of BDD electrode is equal to 3.3 × 10−7 mol L−1 . Analogically, the reduction of OMZ in PBS (pH = 3) was investigated by the same manner as oxidation (Fig. 5C). The baseline corrected LSV response of BDD electrode was found to be linear in the range of 1.2 × 10−5 –6.5 × 10−5 mol L−1 . The calibration curve is depicted in Fig. 5D with following parameters: intercept A = −4.77 × 10−8 A, sA = 1.1 × 10−8 A, slope B = 0.026 A L mol−1 , sB = 0.0012 A L mol−1 , R2 = 0.99. The detection limit was calculated according to above mentioned criterion and it is equal to 5.67 × 10−6 mol L−1 . This value is approximately 17 times higher in comparison with electrooxidation of OMZ. These results motivated us to investigate the electrooxidation and electroreduction of omeprazole with pulse techniques to establish more sensitive sensing platform for its detection. We first optimized parameters for square-wave voltammetry

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Fig. 4. Dependence of LSV peak potential of 1.2 × 10−3 mol L−1 omeprazole solution in 0.1 mol L−1 various supporting electrolytes on scan rate (10, 25, 50, 100, 150, 300 mV s−1 ). A-PBS pH = 3, B-PBS pH = 5, C-PBS pH = 7, D-KCl pH = 7, E-PBS pH = 3, F-PBS pH = 5, G-PBS pH = 7 (A-D for oxidation of OMZ and E-G for reduction of OMZ). Background was subtracted.

analogically as in our previous work [24] and the highest SW signal was observed at frequency (25 Hz), step potential (5 mV) and pulse amplitude (50 mV). At these parameters anodic SW voltammograms were recorded in the potential range from 0.6 to 1.6 V vs. Ag/AgCl for various concentration of OMZ (Fig. 5E). The SW signal was found to be linear in the concentration range of 1.2 × 10−6 –6.9 × 10−6 mol L−1 (Fig. 5F) with these parameters: intercept A = 8.7 × 10−8 A, sA = 1.5 × 10−8 A, slope B = 0.1 A L mol−1 , sB = 0.0033 A L mol−1 , R2 = 0.991. The detection limit of 9.1 × 10−8 mol L−1 was calculated according to 3snoise /B criterion. Finally, electroreduction of OMZ was investigated by square wave voltammetry, but signal was not sufficiently developed so differential pulse voltammetry was applied. Using this procedure well defined cathodic signal of OMZ was obtained and LOD of method was estimated about one order higher than by SWV. The repeatability of proposed methods (SWV and DPV) was studied by ten consecutive measurements under the same operating conditions

and relative standard deviation for both techniques was less than 5%. Before validation of this analytical strategy we investigated also the influence of possible interferents on signal of 5 × 10−6 mol L−1 OMZ. It was observed that the cathodic and anodic peak of OMZ has statistically the same magnitude in 100-fold excess of Na+ and K+ and in 50-fold excess of Pb2+ , Fe3+ . Glucose, starch, urea and ascorbic acid do not interfere in 10-fold excess. Then, nine model samples were analyzed with both proposed techniques (see Table 3). The content of OMZ was several times higher than the limit of detection of technique. The difference between given and found values is statistically acceptable together with standard deviations and coverage interval for 95% probability. In the next experiments three samples of human urine were spiked with omeprazole and analyzed. As can be seen from Table 4 the recoveries are in the range of 96–103% indicating that proposed analytical strategies are suitable for real samples analysis. Pharmaceutical formulations and human urine served as real samples.

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Fig. 5. A: Linear sweep voltammograms of oxidation for 10 ␮L of 5.8 × 10−3 mol L−1 OMZ additions in 0.1 mol L−1 phosphate buffer solutions (pH = 10). Concentrations of OMZ: (0) 0, (1) 2.3 × 10−6 , (2) 4.6 × 10−6 , (3) 6.9 × 10−6 , (4) 9.3 × 10−6 , (5) 1.2 × 10−5 and (6) 1.4 × 10−5 mol L−1 of OMZ on BDD electrode. Scan rate 50 mV s−1 . Background was subtracted. B: Calibration curve for this experiment. Linearity was verified by F-test. C: Linear sweep voltammograms of reduction for 50 ␮L of 5.8 × 10−3 mol L−1 OMZ additions in 0.1 mol L−1 phosphate buffer solutions (pH = 3). Concentrations of OMZ: (0) 0, (1) 1.2 × 10−5 , (2) 2.3 × 10−5 , (3) 3.5 × 10−5 , (4) 4.6 × 10−5 , (5) 5.7 × 10−5 and (6) 6.9 × 10−5 mol L−1 of OMZ on BDD electrode. Scan rate 100 mV s−1 . Background was subtracted. D: Calibration curve for this experiment. Linearity was verified by F-test. E: Square-wave voltammograms of oxidation for 5 ␮L of 5.8 × 10−3 mol L−1 OMZ additions in 0.1 mol L−1 phosphate

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Table 3 Analysis of OMZ model samples (6 parallel determinations). OMZ 106 [mol L−1 ]

OMZ found Method A 106 [mol L−1 ]

SD 106 [mol L−1 ]

OMZ found Method B 106 [mol L−1 ]

SD 106 [mol L−1 ]

OMZ found Method C 106 [mol L−1 ]

SD 106 [mol L−1 ]

OMZ found Method D 106 [mol L−1 ]

SD 106 [mol L−1 ]

1.2 2.3 4.6 6.9 9.3 12 23 46 57

– 2.5 ± 0.2 4.7 ± 0.2 6.8 ± 0.1 9.4 ± 0.2 11.4 ± 0.6 – – –

– 0.3 0.2 0.2 0.2 0.8 – – –

– – – – – 13.0 ± 1.0 25.1 ± 1.3 44.5 ± 2.1 55.6 ± 1.9

– – – – – 1.2 1.6 2.5 2.3

1.1 ± 0.2 2.2 ± 0.1 4.7 ± 0.1 6.8 ± 0.1 – – – – –

0.2 0.1 0.2 0.1 – – – – –

– 2.5 ± 0.2 4.5 ± 0.3 6.8 ± 0.2 9.1 ± 0.3 11.3 ± 0.9 – – –

– 0.3 0.3 0.3 0.3 1.1 – – –

Method A: LSV (oxidation), Method B: LSV (reduction), Method C: SWV, Method D: DPV. The coverage interval for 95% probability: x¯ ± tn−1,␣ SD/n1/2 (t5;0.05 = 2.0150). Table 4 OMZ analysis in human urine spiked samples (n = 6). Added 106 [mol L−1 ]

Found Method A 106 [mol L−1 ]

SD 106 [mol L−1 ]

Recovery [%]

Found Method B 106 [mol L−1 ]

SD 106 [mol L−1 ]

Recovery [%]

10 15 20

10.2 ± 0.3 14.6 ± 0.4 19.3 ± 0.8

0.3 0.5 1.0

102.3 97.1 96.5

9.9 ± 0.2 15.4 ± 0.5 20.6 ± 0.7

0.2 0.6 0.9

98.6 102.5 102.9

Method A: SWV, Method B: DPV. The coverage interval for 95% probability: x¯ ± tn−1,␣ SD/n1/2 (t5;0.05 = 2.0150). Table 5 Real sample analysis of OMZ (n = 3). Real sample

Found Method A [mg]

SD [mg]

Found Method B [mg]

SD [mg]

Declared by manufacturer [mg]

SD [mg]

Helicid® (Zentiva, CZE) Omeprazol® (Sandoz, SLO) Human urine*

18.9 20.8 6.2 × 10−6

1.0 1.0 5 × 10−7

21.0 19.1 6.4 × 10−6

1.5 1.4 6.5 × 10−7

20 20 6.3 × 10−6 **

– – 3 × 10−7 **

Method A: SWV, Method B: DPV. * all data in this row are in mol L−1 . ** determined by HPLC-UV as independent technique. Table 6 Electrochemical methods for the detection of omeprazole. Method

Electrode

LOD [␮mol L−1 ]

LDR [␮mol L−1 ]

Sensitivity

Ref.

AdSV AdSV AdSV DPV DPP SWV SWV DPV

HMDE HMDE HMDE CPE DME EPG BDDE BDDE

0.0065 0.0025 0.0036 0.025 0.07 19 0.091 0.91

0.0083–0.14 0.02–0.44 0.02–0.35 0.2–50 0.1–1 1–100 1.2–6.9 2.3–14

0.0239 ␮A ␮L mol−1 36.52 ␮A ␮L mol−1 47.42 ␮A ␮L mol−1 490.6 nA ␮L mol−1 – 0.1549 ␮A ␮L mol−1 0.1 A L mol−1 0.01 A L mol−1

[25] [26] [26] [27] [28] [29] This paper This paper

AdSV: adsorptive stripping voltammetry, BDDE: boron-doped diamond electrode, CPE: carbon paste electrode, DME: dropping mercury electrode, DPP: differential pulse polarography, DPV: differential pulse voltammetry, EPG: edge-plane pyrolytic graphite, HMDE: hanging mercury drop electrode, LDR: linear dynamic range, LOD: limit of detection, SWV: square-wave voltammetry.

The results of real samples analysis are summarized in Table 5. The results are in statistical agreement with results declared by manufacturer or with data obtained with HPLC-UV as independent method routinely used for omeprazole detection in urine. Survey of analytical methods for the detection of OMZ is summarized in Table 6 [25–29]. From this table it is evident that AdSV based on mercury electrodes has been mostly dominated in electrochemical determination of OMZ because their high sensitivity. However, SWV technique based on boron-doped diamond electrode with one order higher detection limit represents environmentally acceptable electrochemical sensor for determination of OMZ with saved posi-

tive analytical attributes (rapidity, simplicity, repeatability and low cost). 5. Conclusions In this work unmodified boron-doped diamond electrode was used for voltammetric investigation of omeprazole as biologically and pharmaceutically important organic molecule. Anodic and cathodic signals of target species on boron-doped diamond surface were recorded. Oxidation and reduction of omeprazole is controlled by diffusion. Its kinetics was characterized formal potentials (+1.07–+0.89 V for oxidation and −0.95 to −1.18 V for omeprazole

buffer solutions (pH = 10). Concentrations of OMZ: (0) 0, (1) 1.2 × 10−6 , (2) 2.3 × 10−6 , (3) 3.5 × 10−6 , (4) 4.6 × 10−6 , (5) 5.7 × 10−6 and (6) 6.9 × 10−6 mol L−1 of OMZ on BDD electrode. Parameters: step potential 5 mV, modulation amplitude 50 mV and frequency 25 Hz. Background was subtracted. F: Calibration curve for this experiment. Linearity was verified by F-test.

Please cite this article in press as: Z. Chomisteková, et al., Oxidation and reduction of omeprazole on boron-doped diamond electrode: Mechanistic, kinetic and sensing performance studies, Sens. Actuators B: Chem. (2016), http://dx.doi.org/10.1016/j.snb.2016.10.014

G Model SNB-21072; No. of Pages 9

ARTICLE IN PRESS Z. Chomisteková et al. / Sensors and Actuators B xxx (2016) xxx–xxx

reduction), charge transfer coefficients (0.52–0.33 for oxidation and 0.19–0.17 for reduction) together with standard heterogeneous rate constants of order 10−3 –10−4 cm s−1 . The sensing performance of this methodology was studied with background corrected linear sweep voltammetry and more sensitive pulse techniques such as square-wave and differential pulse voltammetry. The signal magnitude is strongly dependent on pH of supporting electrolyte. The lowest detection limit 9.1 × 10−8 mol L−1 for omeprazole oxidation was reached by SWV in PBS with pH of 10. This detection platform was validated on model and spiked samples. Pharmaceutical formulations of omeprazole and human urine as an example of more complex matrix served as real samples. The results are in statistical agreement with the values declared by manufacturer and in the case of human urine with results obtained by HPLC as independent technique.

[18] [19] [20]

[21]

[22] [23]

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Acknowledgements This study was supported by the GAPF Agency of Faculty of Education, The Catholic University in Ruˇzomberok under the project No. GAPF 1/19/2015.

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Biographies Zuzana Chomisteková is PhD student of analytical chemistry in the Laboratory of electroanalytical chemistry at Catholic University in Ruˇzomberok Slovakia. Her main research interests are electrochemical sensors based on boron-doped diamond electrode as detection tool for organic and inorganic molecules. Eva Culková is an assistant professor at the Depatrment of Chemistry and Physics of Catholic University in Ruˇzomberok, Slovakia. Her major research focuses on development of electroanalytical methods for detection of heavy metals in environmental samples using solid electrode materials based on carbon. Renata Bellová is currently working at the Department of Chemistry and Physics of Catholic University in Ruˇzomberok. She obtained her PhD. in theory of teaching specialized subjects focussed to teaching of applied chemistry. She is the author of 1 monograph and co-author of 13 university textbooks, 15 domestic and foreign articles. Danica Melicherˇcíková is an associate profesor of chemistry teaching at the department of chemistry and physisc of the Catholic University in Ruˇzomberok, Slovakia. Her work is devoted to the issue of the effects of chemicals on the human body. Jaroslav Durdiak is an asistant professor at the Department of Chemistry and Physics at the Catholic university in Ruˇzomberok. His work is aimed to the toxicology of organic and inorganic molecules Jaroslav Timko is head of the Department of laboratory methods at the Faculty of Health of the Catholic university in Ruˇzomberok. His scientific interests are microbiology and biological samples treatment. Miroslav Rievaj is an associate profesor at the Department of chemistry and physics at the Catholic University in Ruˇzomberok where he moved from Slovak University of Technology in Bratislava. Peter Tomˇcík obtained his PhD in analytical chemistry/electrochemistry at Slovak University of Technology in Bratislava, Slovakia in 1999 and spent two years at Oxford University in RGC group. Currently he is professor of chemistry and head of Chemistry and physics department at Catholic University in Ruˇzomberok, Slovakia. He is a continuator of Slovak electrochemistry school focusing his research to analytical techniques development using amperometric sensors for the detection of important compounds from environment, biology and pharmacy. He is a co-author of 49 papers published in periodicals with non-zero impact factor. To date, his citation record on above mentioned papers is 511 indexed citations.

Please cite this article in press as: Z. Chomisteková, et al., Oxidation and reduction of omeprazole on boron-doped diamond electrode: Mechanistic, kinetic and sensing performance studies, Sens. Actuators B: Chem. (2016), http://dx.doi.org/10.1016/j.snb.2016.10.014