Voltammetric Determination of Hydroxychloroquine Used in the Treatment of COVID‐19 at MWCNT Modified Pencil Graphite Electrode

Year 2025, Volume: 21 Issue: 3, 121 - 130, 26.09.2025

Sultan Hasankahyaoğlu , Şevval Sazlık , İrem Demir , Selen Ayaz , Didem Giray Dilgin

https://doi.org/10.18466/cbayarfbe.1705373

Abstract

COVID-19, the most significant pandemic of the 21st century, has prompted the use of various drugs to slow down the viral process in patients infected with it. One of these drugs is hydroxychloroquine, and due to its importance and frequent use in the treatment of COVID-19, its rapid, accurate and inexpensive determination in biological or pharmaceutical samples is very important. In this study, the electrochemical behavior of hydroxychloroquine was investigated, and voltammetric determination of hydroxychloroquine was performed with a pencil graphite electrode modified with multi-walled carbon nanotubes. Scanning electron microscopy images were used to examine the surfaces of both the regular pencil graphite electrode and the modified one with multi-walled carbon nanotube. Cyclic voltammetric measurements showed that hydroxychloroquine was irreversibly oxidized at approximately +700 and +900 mV in Britton Robinson buffer solution at pH 10.0. Considering these oxidation peaks, differential pulse voltammetric determination of hydroxychloroquine was carried out under optimized conditions. A linear response was obtained from the multi-walled carbon nanotube-modified pencil graphite electrode in the range of 0.1 to 200 µmolL-1 for peaks at both +700 mV and +900 mV with detection limits of 0.04 and 0.05 µmolL-1, respectively. The method was tested on the real tablet and water samples; nearly 100 % recovery was achieved for hydroxychloroquine spiked into the water sample, while the amount of the labeled compound in the pharmaceutical tablet was accurately determined. This result confirmed that the multi-walled carbon nanotube-modified pencil graphite electrode is very effective for selectively and accurately determining hydroxychloroquine in real samples.

Keywords

Differential pulse voltammetry , Electrochemical detection , Hydroxychloroquine , Multi-walled carbon nanotube , Pencil graphite electrode.

References

• [1]. WHO, WHO Director-General's opening remarks at the media briefing on COVID-19. https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020/, 11 Mach 2020 (accessed at 23.05.2025).
• [2]. WHO, WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/, 9 November 2022 (accessed at 23.05.2025).
• [3]. Stasi, C, Fallani, S, Voller, F, Silvestri, C. 2020. Treatment for COVID-19: An overview. European Journal of Pharmacology; 889: 173644.
• [4]. Sinha, N, Balayla, G. 2020. Hydroxychloroquine and COVID-19. Postgraduate Medical Journal; 96: 550–555.
• [5]. Fox, RI. 1993. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Seminars in Arthritis and Rheumatism; 23(2): 82-91.
• [6]. Ferner, RE, Aronson, JK. 2020. Chloroquine and hydroxychloroquine in COVID-19. BMJ; 369: m1432.
• [7]. The RECOVERY Collaborative Group. 2020. Effect of hydroxychloroquine in hospitalized patients with COVID-19. The New England Journal of Medicine; 383(21): 2030-2040.
• [8]. WHO, WHO solidarity trial consortium, repurposed antiviral drugs for COVID-19 — interim who solidarity trial results. 2021. The New England Journal of Medicine; 384(6): 497-511.
• [9]. Bhati, KN, Mashru, R. 2022. Development and validation of extractive spectrophotometric method for estimation of hydroxychloroquine sulphate by using smartphone application. Journal of Drug Delivery & Therapeutics; 12(3): 49-56.
• [10]. Sura, SALD, Samarray, SYAL. 2022. Determination spectrophotometric and cloud point extraction of hydroxychloroquine sulfate. HIV Nursing; 22(2): 2900-2904.
• [11]. Ramzy, S, Abdelazim, AH, Osman, AOE, Hasan, MA. 2022. Spectrofluorimetric quantitative analysis of favipiravir, remdesivir and hydroxychloroquine in spiked human plasma. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy; 281: 121625.
• [12]. El Sharkasy, ME, Tolba, MM, Belal, F, Walash, M, Aboshabana, R. 2022. Quantitative analysis of favipiravir and hydroxychloroquine asFDA-approved drugs for treatment of COVID-19 usingsynchronous spectrofluorimetry: application to pharmaceuticalformulations and biological fluids. Luminescence; 37: 953-964.
• [13]. Bodur, S, Erarpat, S, Günkara, OT, Bakırdere, B. 2021. Accurate and sensitive determination of hydroxychloroquine sulfate used on COVID-19 patients in human urine, serum and saliva samples by GC-MS. Journal of Pharmaceutical Analysis; 11: 278-283.
• [14]. Sok, V, Marzan, F, Gingrich, D, Aweeka, F, Huang, L. 2021. Development and validation of an LC-MS/MS method for determination of hydroxychloroquine, its two metabolites, and azithromycin in EDTA-treated human plasma. PLoS ONE; 16(3): e0247356.
• [15]. Volin, P. 1995. Simple and specific reversed-phase liquid chromatographic method with diode-array detection for simultaneous determination of serum hydroxychloroquine, chloroquine and some corticosteroids. Journal of Chromatography B; 666: 347-353.
• [16]. Bilgin, ZD, Evcil, I, Yazgi, D, Binay, G, Genc, CO, Gulsen, B, Huseynova, A, Ozdemir, AZ, Ozmen, E, Usta, Y, Ustun, S, Andac, SC. 2021. Liquid chromatographic methods for COVID-19 drugs, hydroxychloroquine and chloroquine. Journal of Chromatographic Science; 59(8): 748-757.
• [17]. Oliveira, ARM, Cardoso, CD, Bonato, PS. 2007. Stereoselective determination ofhydroxychloroquine and its metabolitesin human urine by liquid-phasemicroextraction and CE. Electrophoresis; 28: 1081-1091.
• [18]. Deroco, PB, Vicentini, FC, Oliveira, GG, Rocha-Filho, RC, Fatibello-Filho, O. 2014. Square-wave voltammetric determination of hydroxychloroquine in pharmaceutical and synthetic urine samples using a cathodically pretreated boron-doped diamond electrode. Journal of Electroanalytical Chemistry; 719: 19-23.
• [19]. de Araújo, DM, Paiva, SDSM, Henrique, JMM, Martínez-Huitle, CA, Dos Santos, EV. 2021. Green composite sensor for monitoring hydroxychloroquine in different water matrix. Materials; 14: 4990.
• [20]. Silva, JPC, Neto, DRS, Lopes, CEC, Silva, LRG, Dantas, LMF, da Silva, IS. 2025. A high sensitivity adsorptive electrochemical method for rapid and portable determination of hydroxychloroquine. Journal of Solid State Electrochemistry; 29: 1013-1023.
• [21]. Arguelho, MLPM, Andrade, JF, Stradiotto, NR. 2023. Electrochemical study of hydroxychloroquine and its determination in plaquenil by differential pulse voltammetry. Journal of Pharmaceutical and Biomedical Analysis; 32: 269-275.
• [22]. Carvalho, MS, Rocha, RG, de Faria, LV, Richter, EM, Dantas, LMF, da Silva, IS, Munoz, RAA. 2022. Additively manufactured electrodes for the electrochemical detection of hydroxychloroquine. Talanta; 250: 123727.
• [23]. Feitosa, MHA, Santos, AM, Wong, A, Sotomayor, MDPT, Barros, WRP, Lanza, MRV, Moraes, FC. 2025. Enhancing hydroxychloroquine detection using carbon paste electrode modifed with platinum nanoparticles and MWCNTs. Journal of Applied Electrochemistry; 55: 2265-2276.
• [24]. Matrouf, M, Loudiki, A, Azriouil, M, Laghrib, F, Ait Akbour, R, Farahi, A, Bakasse, M, Saqrane, S, Lahrich, S, El Mhammedi, MA. 2022. Electrochemical behavior of hydroxychloroquine on natural phosphate and its determination in pharmaceuticals and biological media. Materials Chemistry and Physics; 287: 126340.
• [25]. Khoobi, A, Ghoreishi, SM, Behpour, M, Shaterian, M, Salavati-Niasari, M. 2014. Design and evaluation of a highly sensitive nanostructure-based surface modification of glassy carbon electrode for electrochemical studies of hydroxychloroquine in the presence of acetaminophen. Colloids and Surfaces B: Biointerfaces; 123: 648-656.
• [26]. Pushpanjali, PA, Manjunatha, JG, Hareesha, N, Girish, T, Al Kahtani, AA, Tighezza, AM, Ataollahi, N. 2025. Electrocatalytic determination of hydroxychloroquine using sodium dodecyl sulphate modifed carbon nanotube paste electrode. Topics in Catalysis; 8, 1373-1381.
• [27]. Matrouf, M, Loudiki, A, Ouatmane, FZ, Chhaibi, B, Alaoui, OT, Laghrib, F, Farahi, A, Bakasse, M, Lahrich, S, El Mhammedi, MA. 2022. Effect of graphite exfoliation way on the efficiency of exfoliated graphene for the determination of hydroxychloroquine in urine and waste water. Journal of the Electrochemical Society; 169: 097505.
• [28]. Silva, MNT, Alves, DAC, Richter, EM, Munoz, RAA, Nossol, E. 2023. A simple, fast, portable and selective system using carbon nanotubes films and a 3D-printed device for monitoring hydroxychloroquine in environmental samples. Talanta; 265: 124810.
• [29]. Khalil, MM, Issab YM, El Sayeda GA. 2015. Modified carbon paste and polymeric membrane electrodes for determination of hydroxychloroquine sulfate in pharmaceutical preparations and human urine. RSC Advances; 5: 83657-83667.
• [30]. Zoubir, J, Bakas, I, Qourza, S, Tamimi, M, Assabbane, A. 2023. Electrochemical sensor based on a ZnO doped graphitized carbon for the electrocatalytic detection of the antibiotic hydroxychloroquine. Application: tap water and human urine. Journal of Applied Electrochemistry; 53: 1279-1294.
• [31]. Vural, K, Karakaya, S, Dilgin, DG, Gokçel, HI, Dilgin, Y. 2023. Voltammetric determination of Molnupiravir used in treatment of the COVID-19 at magnetite nanoparticle modified carbon paste electrode. Microchemical Journal; 184: 108195.
• [32]. David, IG, Buleandra, M, Popa, DE, Cheregi, MC, David, V, Iorgulescu, EE, Tartareanu, G.O. 2022. Recent developments in voltammetric analysis of pharmaceuticals using disposable pencil graphite electrodes. Processes; 10: 472.
• [33]. Günes, M, Karakaya, S, Kocaaga, T, Yıldırım, F, Dilgin, Y. 2021. Sensitive voltammetric determination of oxymetazoline hydrochloride at a disposable electrode. Monatshefte für Chemie - Chemical Monthly; 152: 1505-1513.
• [34]. Brycht, M, Konecka, K, Sipa, K, Skrzypek, S, Mirˇceski, V. 2019. Electroanalysis of the anthelmintic drug bithionol at edge plane pyrolytic graphite electrode. Electroanalysis; 31: 2246–2253.
• [35]. Karakaya, S, Dilgin, Y. 2023. The application of multi walled carbon nanotubes modifed pencil graphite electrode for voltammetric determination of favipiravir used in COVID 19 treatment. Monatshefte für Chemie - Chemical Monthly; 154: 729-739.