A Box-Behnken Optimized Methodology for the Quantification of Diclofenac using a Carbon Paste-Multiwalled Carbon Nanotubes Electrode

Author(s): Miriam Franco Guzmán, Luis Humberto Mendoza Huizar, Carlos Andrés Galán Vidal, Gabriela Roa Morales, Giaan A. Álvarez Romero*.

Journal Name: Current Analytical Chemistry

Volume 15 , Issue 3 , 2019

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Graphical Abstract:


Background: Diclofenac is a widely used nonsteroidal anti-inflammatory drug. Recent studies have shown that frequent consumption of this drug in high concentrations can cause heart diseases, so strict control of diclofenac’s quantity in commercial drugs is necessary. This paper presents the development of an optimized voltammetric methodology for the quantification of diclofenac, which offers some advantages over other electrochemical and accepted methods.

Objective: Optimize with a Box-Behnken design the differential pulse voltammetry parameters towards the quantification of diclofenac in pharmaceutical samples.

Methods: Diclofenac behavior in the working electrode was evaluated by cyclic voltammetry, in order to stablish the best conditions for diclofenac’s quantification. A Box-Behnken design was then used to optimize the differential pulse voltammetry parameters and stablish the analytical behavior of the proposed methodology. Commercial tablets were prepared for analysis according to the Pharmacopeia, the DPV optimized methodology was used to quantify diclofenac in the samples, and the results were statistically compared with those obtained with the official methodology.

Results: After optimization, the analytical parameters found were: correlation coefficient of 0.998, detection limit of 0.001 µM, quantification limit of 0.0033 µM and sensitivity of 0.299 µA.µM-1. The statistical analysis showed there were no significant differences between the results obtained with the proposed methodology and those obtained with the official methodology.

Conclusion: The statistical analysis showed that the proposed methodology is as reliable as the official spectrophotometric one for the quantification of diclofenac in commercial drugs, with very competitive analytical parameters, and even better to others found with more complex electrodes.

Keywords: Box-behnken optimization, carbon paste electrode, diclofenac, differential pulse voltammetry, multiwalled carbon nanotubes, pharmaceutical samples.

Afkhami, A.; Bahiraei, A.; Madrakian, T. Gold nanoparticle/multi-walled carbon nanotube modified glassy carbon electrode as a sensitive voltammetric sensor for the determination of diclofenac sodium. Mater. Sci. Eng. C, 2016, 59, 168-176.
Goyal, R.N.; Chatterjee, S.; Agrawal, B. Electrochemical investigations of diclofenac at edge plane pyrolytic graphite electrode and its determination in human urine. Sens. Actuators B ., 2010, 145(2), 743-748.
Kormosh, Z.; Hunka, I.; Bazel, Y. Potentiometric determination of diclofenac in pharmaceutical formulation by membrane electrode based on ion associate with base dye. Chin. Chem. Lett., 2007, 18, 1103-1106.
Sanati, A.L.; Karimi-Maleh, H.; Badiei, A.R.; Biparva, P.; Ensafi, A.A. A voltammetric sensor based on NiO/CNTs ionic liquid carbon paste electrode for determination of morphine in the presence of diclofenac. Mater. Sci. Eng. C, 2014, 35, 379-385.
Goyal, R.N.; Chatterjee, S.; Rana, A.R.S. The effect of modifying an edge-plane pyrolytic graphite electrode with single-wall carbon nanotubes on its use for sensing diclofenac. Carbon, 2010, 48, 4136-4144.
Sondergaard, K.B.; Weeke, P.; Wissenberg, M.; Schjerning Olsen, A.M.; Fosbol, E.L.; Lipper, F.K.; Torp-Pedersen, C.; Gislason, G.H. Folke Fredrik. Non-steroidal anti-inflamatory drug use is associated with increased risk of out-of-hospital cardiac arrest: a nationwide case-time-control study. Eur. Heart J. Cardiovasc. Pharmacother., 2017, 3(2), 100-107.
Mokhtari, A.; Karimi-Maleh, H.; Ensafi, A.A.; Beitollahi, H. Application of modified multiwall carbon nanotubes paste electrode for simultaneous voltammetric determination of morphine and diclofenac in biological and pharmaceutical samples. Sens. Actuators B., 2012, 169, 96-105.
Yilmaz, B.; Ciltas, U. Determination of diclofenac in pharmaceutical preparations by voltammetry and gas chromatography methods. J. Pharm. Anal., 2015, 5(3), 153-160.
Tubino, M.; Souza, R.L. Gravimetric method for the determination of diclofenac in pharmaceutical preparations. J. AOAC Int., 2005, 88(6), 1684-1687.
Shamsipur, M.; Jalali, F.; Ershad, S. Preparation of a diclofenac potentiometric sensor and its application to pharmaceutical analysis and to drug recovery from biological fluids. J. Pharm. Biomed, 2005, 37(5), 943-947.
Santini, A.O.; Pezza, H.R.; Pezza, L. Determination of diclofenac in pharmaceutical preparations using a potentiometric sensor immobilized in a graphite matrix. Talanta, 2006, 68(3), 636-642.
Hassan, S.S.M.; Mahmoud, W.H.; Elmosallany, M.A.F. Iron (II)-phthalocyanine as a novel recognition sensor for selective potentiometric determination of diclofenac and warfarin drugs. J. Pharm. Biomed., 2005, 39, 315-321.
Jin, W.; Zhang, J. Determination of diclofenac sodium by capillary zone electrophoresis with electrochemical detection. J. Chromatogr. A, 2000, 868(1), 101-107.
Yilmaz, B.; Asci, A.; Palabiyik, S.S. HPLC method for determination of diclofenac in human plasma and its application to a pharmacokinetic study in Tukey. J. Chromatogr. Sci., 2011, 49, 422-427.
Arcelloni, C.; Lanzi, R.; Pedercini, S. High-performance liquid chromatographic determination of diclofenac in human plasma after solid-phase extraction. J. Chromatogr. B., 2001, 763, 195-200.
Meng, Q.C.; Cepeda, M.S.; Kramer, T.; Zou, H.; Matoka, D.J.; Farrar, J. High performance liquid chromatographic determination of morphine and its 3- and 6-glucuronide metabolites by two-step solid-phase extraction. J. Chromatogr. B Biomed. Sci. Appl., 2000, 742, 115-123.
Elkady, E.F. Simultaneous determination of diclofenac potassium and methocarbamol in ternary mixture with guaifenesin by reversed phase liquid chromatography. Talanta, 2010, 82(4), 1604-1607.
Bhupendra, L.K.; Kaphalia, S.; Kumar, S.; Kanz, M.F.; Treinen-Moslen, M. Efficient high performance liquid chromatograph/ultraviolet method for determination of diclofenac and 4′-hydroxydiclofenac in rat serum. J. Chromatogr. B., 2005, 830(2), 231-237.
Lee, H.S.; Jeong, C.K.; Choi, S.J.; Kim, S.B.; Lee, M.H.; Ko, G.; Sohn, D.H. Simultaneous determination of aceclofenac and diclofenac in human plasma by narrow bore HPLC using column-switching. J. Pharm. Biomed. Anal., 2000, 23(5), 775-781.
Roskar, R.; Kmetec, V. Liquid chromatographic determination of diclofenac in human sinovial fluid. J. Chromatogr. B ., 2003, 788(1), 57-64.
Birajdar, A.S.; Meyyanathan, S.; Suresh, B. A RP-HPLC method for determination of diclofenac with rabeprazole in solid dosage form. Pharm Sci. Monit, 2011, 2(2), 171-178.
Chmielewska, A.; Konieczna, L.; Plenis, A.; Bieniecki, M.; Lamparczyk, H. Determination of diclofenac in plasma by high-performance liquid chromatography with electrochemical detection. Biomed. Chromatogr., 2006, 20(1), 119-124.
Mukherjee, B.; Mahapatra, S.; Das, S.; Roy, G.; Dey, S. HPLC detection of plasma concentrations of diclofenac in human volunteers administered with povidone-ethylcellulose-based experimental transdermal matrix-type patches. Methods Find. Exp. Clin. Pharmacol., 2006, 28(5), 301-306.
Abdel-Hamid, M.E.; Novotny, L.; Hamza, H.J. Determination of diclofenac sodium, flefenamic acid, indomethacin and ketoprofen by LC-APCI-MS. J. Pharm. Biomed. Anal., 2001, 24(4), 587-594.
Quintana, J.B.; Carpinteira, J.; Rodrigues, I. Chapter 2.5 Analysis of acidic drugs by gas chromatography. Comprehensive. Anal. Chem., 2007, 50, 185-218.
Yilmaz, B. GC-MS determination of diclofenac in human plasma. Chromatographia, 2010, 71(5-6), 549-551.
Thongchai, W.; Liawruangrath, B.; Thongpoon, C.; Machan, T. High performance thin layer chromatographic method for the determination of diclofenac sodium in pharmaceutical formulations. Chiang Mai. J. Sci., 2006, 33(1), 123-128.
Bhushan, R.; Gupta, D.; Mukherjee, A. Liquid chromatographic analysis of certain commercial formulations for non-opioid analgesics. Biomed. Chromatogr., 2007, 21(12), 1284-1290.
Sparidans, R.W.; Lagas, J.S.; Schinkel, A.H.; Schellens, J.H.M.; Beijnen, J.H. Liquid chromatography-tandem mass spectrometric assay for diclofenac and three primary metabolites in mouse plasma. J. Chromatogr. B., 2008, 872(1-2), 77-82.
De Souza, R.L.; Tubino, M. Spectrophotometric determination of diclofenac in pharmaceutical preparations. J. Braz. Chem. Soc., 2005, 16(5), 1068-1073.
Didamony, A.M.; Amin, A.S. Adaptation of a color reaction for spectrophotometric determination of diclofenac sodium and piroxicam in pure form and in pharmaceutical formulations. Anal. Lett., 2004, 37(6), 1151-1162.
Matin, A.A.; Farajzadeh, M.A.; Joyuban, A. A simple spectrophotometric method for determination of sodium diclofenac in pharmaceutical formulations. II Farmaco, 2005, 60(10), 855-858.
Gabhane, K.B.; Kasture, A.V.; Shrikhande, V.N.; Barde, L.N.; Wankhade, V.P. Simultaneous spectrophotometric determination of metaxalone and diclofenac potassium in combined tablet dosage form. Int. J. Chem. Sci, 2009, 7(1), 539-545.
Arancibia, J.A.; Boldrini, M.A.; Escandar, G.M. Spectrofluorimetric determination of diclofenac in the presence of α-cyclodextrin. Talanta, 2000, 52(2), 261-268.
Marcela, C.; Liliana, B. Indirect fluorometric determination of diclofenac sodium. Anal. Sci., 2006, 22, 431-433.
Sarhangzadeh, K.; Khatami, A.A.; Jabbari, M.; Bahari, S. Simultaneous determination of diclofenac and indomethacin using a sensitive electrochemical sensor based on multiwalled carbon nanotube and ionic liquid nanocomposite. J. Appl. Electrochem., 2013, 43(12), 1217-1224.
Arvand, M.; Gholizadeh, T.M.; Zanjanchi, M.A. MWCNTs/Cu(OH)2 nanoparticles/IL nanocomposite modified glassy carbon electrode as a voltammetric sensor for determination of the non-steroidal anti-inflammatory drug diclofenac. Mater. Sci. Eng. C, 2012, 32, 1682-1689.
Yang, X.; Wang, F.; Hu, S. Enhanced oxidation of diclofenac sodium at a nanostructured electrochemical sensing film constructed by multi-wall carbon nanotubes-surfactant composite. Mater. Sci. Eng. C, 2008, 28(1), 188-194.
Goodarzian, M.; Khalilzade, M.A.; Karimi, F.; Gupta, V.K.; Keyvanfard, M.; Bagheri, H.; Fouladgar, M. Square wave voltammetric determination of diclofenac in liquid phase using a novel ionic liquid multiwall carbon nanotubes paste electrode. J. Mol. Liq., 2014, 194, 114-119.
Manea, F.; Ihos, M.; Remes, A.; Burtica, G.; Schoonman, J. Electrochemical determination of diclofenac sodium in aqueous solution on Cu-doped zeolite-expanded graphite-epoxy electrode. Electroanalysis, 2010, 22(17-18), 2058-2063.
Chethana, B.K.; Basavanna, S.; Arthoba Naik, Y. Voltammetric determination of diclofenac sodium using tyrosine-modified carbon paste electrode. Ind. Eng. Chem. Res., 2012, 51(31), 10287-10295.
Fernandez-Llano, L.; Blanco-Lopez, M.C.; Lobo-Castano, M.J.; Miranda-Ordieres, A.J.; Tunon-Blanco, P. Determination of diclofenac in urine samples by molecularly imprinted solid-phase extraction and adsorptive differential pulse voltammetry. Electroanalysis, 2007, 19(15), 1555-1561.
Bayandori Moghaddam, A.; Mohammadi, A.; Fathabadi, M. Application of carbon nanotube-graphite mixture for the determination of diclofenac sodium in pharmaceutical and biological samples. Pharmaceut. Anal. Acta, 2012, 5(3), 1000161-1000166.
Hajjizadeh, M.; Jabbari, A.; Heli, H.; Moosavi-Movahedi, A.A.; Haghgoo, S. Electrocatalytic oxidation of some anti-inflammatory drugs on a nickel hydroxide-modified nickel electrode. Electrochim. Acta, 2007, 53(4), 1766-1774.
Karuppiah, C.; Cheemalapati, S.; Chen, S.M.; Palanisamy, S. Carboxyl-functionalized graphene oxide-modified electrode for the electrochemical determination of nonsteroidal anti-inflammatory drug diclofenac. Ionics, 2015, 21(1), 231-238.
Diclofenaco. Farmacopea de los Estados Unidos Mexicanos, Décima edición 2011, 1162.
Švancara, I.; Schachl, K. Testing of unmodified carbon paste electrodes. Chem. Listy, 1999, 93, 490-499.
Fakhari, A.R.; Rafiee, B.; Ahmar, H.; Bagheri, A. Electrocatalytic determination of oxalic acid by TiO2 nanoparticles/multiwalled carbon nanotubes modified electrode. Anal. Methods, 2012, 4, 3314-3319.
Cuéllar, M.; Pfaffen, V.; Ortiz, P.I. Application of multi-factorial experimental design to successfully model and optimize inorganic chromium speciation by square wave voltammetry. J. Electroanal. Chem., 2016, 765, 37-44.
Thompson, M.; Ellison, S.L.R.; Wood, R. Harmonized guidelines for single-laboratory validation of methods of analysis. Pure Appl. Chem., 2002, 74(5), 835-855.
Cid-Cerón, M.M.; Guzmán-Hernández, D.S.; Ramírez-Silva, M.T.; Galano, A.; Romero-Romo, M.; Palomar-Pardavé, M. New insights on the kinetics and mechanism of the electrochemical oxidation of diclofenac in neutral aqueous medium. Electrochim. Acta, 2016, 199, 92-98.
Aguilar-Lira, G.Y.; Álvarez-Romero, G.A.; Zamora-Suárez, A.; Palomar-Pardavé, M.; Rojas-Hernández, A.; Rodríguez-Ávila, J.A.; Páez-Hernández, M.E. New insights on diclofenac electrochemistry using graphite as working electrode. J. Electroanal. Chem., 2017, 794, 182-188.
Barbier, B. Electrochemical bonding of amines to carbon fiber surfaces toward improved carbon-epoxy composites. J. Electrochem. Soc., 1990, 137(6), 1757-1764.
Deinhammer, R.S.; Ho, M.; Anderegg, J.W. Porter, M.D. Electrochemical Oxidation of Amine-Containing Compounds: A Route to the Surface Modification of Glassy Carbon Electrodes. Langmuir, 1994, 10(4), 1306-1313.
Ensafi, A.A.; Izadi, M.; Karimi-Maleh, H. Sensitive voltammetric determination of diclofenac using room-temperature ionic liquid-modified carbon nanotubes paste electrode. Ionics, 2013, 19(1), 137-144.
Parvizi Fard, G.; Alipour, E.; Ali Sabzi, R.E. Modification of a disposable pencil graphite electrode with multiwalled carbon nanotubes: application to electrochemical determination of diclofenac sodium in some pharmaceutical and biological samples. Anal. Methods, 2016, 8, 3966-3974.
Arvand, M.; Hassannezhad, M. Square wave voltammetric determination of uric acid and diclofenac on multi-walled carbon nanotubes decorated with magnetic core-shell Fe3O4@SiO2 nanoparticles as an enhanced sensing interface. Ionics, 2015, 21, 3245-3256.
Guzmán-Hernández, D.S.; Martínez-Cruz, M.A.; Ramírez-Silva, M.T.; Romero-Romo, M.; Corona-Avendaño, S.; Mendoza-Huizar, L.H.; Palomar-Pardavé, M. Simultaneous electrochemical quantification of naproxen, acetaminophen and diclofenac using a bare carbon paste electrode. Anal. Methods, 2016, 8, 7868-7872.
Guzmán-Hernández, D.S.; Cid-Cerón, M.M.; Romero-Romo, M.; Ramírez-Silva, M.T.; Páez-Hernández, M.E.; Corona-Avendaño, S.; Palomar-Pardavé, M. Taking advantage of CTAB micelles for the simultaneous electrochemical quantification of diclofenac and acetaminophen in aqueous media. RSC Advances, 2017, 7, 40401-40410.

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Year: 2019
Page: [294 - 304]
Pages: 11
DOI: 10.2174/1573411014666180423151749
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