Electrochemical exfoliated graphene oxide nanosheets modified graphite electrode for clozapine sensing

Document Type : Original Article


1 Department of Chemistry, Faculty of Science, University of Guilan. Rasht, Iran

2 Education Organization of Guilan Province, Rasht, Iran

3 Department of Physics, Rasht Branch, Islamic Azad University, Rasht, Iran


Graphene oxide nanosheets (GONs) are ideally suited for implementation in electrochemical applications due to their large electrical conductivity, large surface area and low production costs. In this research, electrochemical exfoliated graphene oxide-modified graphite electrode was developed for voltammetric determination of clozapine (CLZ). The dependence of oxidation peak current on the pH of the solution, scan rate and concentration of analyte were studied to optimize the experimental conditions for electrochemical determination of CLZ. The experimental results suggested that the modified electrode promoted electron transfer reaction for the oxidation of CLZ. The modified electrode exhibited high effective surface area, more reactive sites and excellent electrocatalytic activity toward the oxidation of CLZ. In the concentration range of 0.75–100 µM of CLZ in citrate buffer solution (CBS, pH 6), the anodic peak currents, measured via differential pulse voltammetry (DPV), presented good linear relationship with limit of detection (LOD) of 2.15 nM and good sensitivity of 0.0477 µA µM−1. The proposed method was successfully applied to quantify the amount of CLZ in the blood serum and plasma of schizophrenia patient.


Main Subjects

This is an open access article under the CC-BY-SA 4.0 license.( https://creativecommons.org/licenses/by-sa/4.0/)

[1] Brumfiel, G. (2009). Graphene gets ready for the big time, Nature, 458, 390–391.
[2] Dreyer, D. R., Park, S., Bielawski, C. W., & Ruoff, R. S. (2010). The chemistry of graphene oxide, Chemical Society Reviews, 39, 228–240.
[3] Shamsi, F., Sheibani, A., & Shishehbore, M. R. (2023). Solid phase extraction based on magnetic graphene oxide nanocomposite and ion mobility spectrometry for determination of bupropion, Applied Chemistry, (18)66, 9–26. (in persian)
[4] Gholami, N., & Mahdavi, H. (2023). Synthesis and application of graphene oxide and sulfonated graphene oxide nanoparticles for using in nanofiltration membranes polyether sulfone, Applied Chemistry, (18)66, 225–244. (in persian)
[5] Han, T. H., Huang, Y. K., & Tan, A. T. L. (2011). Steam etched porous graphene oxide network for chemical sensing, Journal of American Chemical Society, 133, 15264–15267.
[6] Pyun, J. (2011). Graphene oxide as catalyst: application of carbon materials beyond nanotechnology, Angewandte Chemie International Edition, 50, 46–48.
[7] Kim, F., Cote, L. J., & Huang, J. X. (2010). Graphene oxide: surface activity and two-dimensional assembly, Advanced Materials, 22, 1954–1958.
[8] Wang, X. L., Bai, H., & Shi, G. Q. (2011). Size fractionation of graphene oxide sheets by pH-assisted selective sedimentation, Journal of American Chemical Society, 133, 6338–6342.
[9] Fan, X. B., Peng, W. C., Li, Y., Li, X., Wang, S., Zhang, G., & Zhang, F. (2008). Deoxygenation of exfoliated graphite oxide under alkaline conditions: a green route to graphene preparation, Advanced Materials, 20, 4490–4493.
[10] Brodie, B. C. (1860). Sur le poids atomique du graphite, Annales de Chimie et de Physique, 59, 466.
[11] Staudenmaier, L. (1898). Verfahrenzur darstellung der graphitsäure, Berichte der Deutschen Chemischen Gesellschaft, 31, 1481–1487.
[12] Hummers, W. S., & Offeman, R. E. (1958). Preparation of graphitic oxide, Journal of American Chemical Society, 80, 1339–1339.
[13] Lotfia, Z., Zavvar Mousavi, H., & Sajjadi, S. M. (2020). Selective ultrasound enhanced removal of anionic dyes from binary mixture using multivariate calibration and central composite design modeling by positively charged hyper branched ammonium functionalized magnetic graphene, Applied Chemistry, (14)53, 67–78. (in persian)
[14] Paredes, J. I., Rodil, S. V., Alonso, A. M., & Tascon, J. M. D. (2008). Graphene oxide dispersions in organic solvents, Langmuir, 24, 10560–10564.
[15] Liu, J., Yang, H., Zhen, S. G., Poh, C. K., Chaurasia, A., Luo, J., Wu, X.,  Yeow, E. K. L., Sahoo, N. G., J., Lin& Shen, Z. (2013). A green approach to the synthesis of high-quality graphene oxide flakes via electrochemical exfoliation of pencil core, RSC Advances, 3, 11745–11750.
[16] Kakaei, K., & Hasanpour, K. (2014). Synthesis of graphene oxide nanosheets by electrochemical exfoliation of graphite in cetyltrimethylammonium bromide and its application for oxygen reduction, Journal of Materials Chemistry A, 2, 15428–15436.
[17] Stephen, H., Schultz, M. D., Stephen, W., & North, M. D. (2007). Schizophrenia, American Family Physician, 75, 1821–1829.
[18] Raggi, M. A., Pucci, V., Bugamelli, F., & Volterra, V. (2001). Comparison of three analytical methods for quality control of clozapine tablets, Journal of AOAC International, 84, 361–367.
[19] Zheng, M. M., Wang, S. T., Hu, W. K., & Feng, Y. Q. (2010). In-tube solid-phase microextraction based on hybrid silica monolith coupled to liquid chromatography-mass spectrometry for automated analysis of ten antidepressants in human urine and plasma, Journal of Chromatography A, 1217, 7493–7501.
[20] Wohlfarth, A., Toepfner, N., Hermanns-Clausen, M., & Auwärter, V. (2011). Sensitive quantification of clozapine and its main metabolites norclozapine and clozapine-N-oxide in serum and urine using LC-MS/MS after simple liquid–liquid extraction work-up, Analytical and Bioanalytical Chemistry, 400, 737–746.
[21] Zhang, G., Jr, A. V. T., & Bartlett, M. J. (2007).  Simultaneous determination of five antipsychotic drugs in rat plasma by high performance liquid chromatography with ultraviolet detection, Journal of Chromatography B, 856, 20–28.
[22] Jin, W., Xu, Q., & Li, W. (2000). Determination of clozapine by capillary zone electrophoresis following end-column amperometric detection with simplified capillary/electrode alignment, Electrophoresis, 21, 1415–1418.
[23] Vardakou, I., Dona, A., Pistos, C., Alevisopoulos, G., Athanaselis, S., Maravelias, C., & Spiliopoulou, C. (2010). Validated GC/MS method for the simultaneous determination of clozapine and norclozapine in human plasma. Application in psychiatric patients under clozapine treatment, Journal of Chromatography B, 878, 2327–2332.
[24] Mohamed, A. A., & Al-Ghannam, S. M. (2004). Spectrophotometric determination of clozapine based on its oxidation with bromate in a micellar medium, Farmaco, 59, 907–911.
[25] Hernandez, L., Gonzalez, E., & Hernandez, P. (1988). Determination of clozapine by adsorptive anodic voltammetry using glassy carbon and modified carbon paste electrodes, Analyst, 113, 1715–1718.
[26] Farhadi, K., & Karimpour, A. (2007). Electrochemical behavior and determination of clozapine on a glassy carbon electrode modified by electrochemical oxidation, Analytical Sciences, 23, 479–483.
[27] Manjunatha, J. G., Swamy, B. E. K., Mamatha, G. P., Gilbert, O., Srinivas, M. T., & Sherigara, B. S. (2011). Electrochemical studies of clozapine drug using carbon nanotube-SDS modified carbon paste electrode: a cyclic voltammetry study, Der Pharma Chemica, 3, 236–249.
[28] Blankert, B., Dominguez, O., Ayyas, W. E., Arcos, J., & Kauffmann, J. M. (2004). Horseradish peroxidase electrode for the analysis of clozapine, Analytical Letters, 37, 903–916.
[29] Attas, A. S. A. (2009). Novel PVC membrane selective electrode for the determination of clozapine in pharmaceutical preparations, International Journal of Electrochemical Science, 4, 9–19.
[30] Huang, F., Qu, S., Zhang, S., Liu, B., & Kong, J. (2007). Sensitive detection of clozapine using a gold electrode modified with 16-mercaptohexadecanoic acid self-assembled monolayer, Talanta, 72, 457–462.
[31] Zeng, F., Sun, Z., Sang, X., Diamond, D., Lau, K. T., Liu, X., & Su, D. S. (2011). In situ one-step electrochemical preparation of graphene oxide nanosheet-modified electrodes for biosensors, ChemSusChem, 4, 1587–1591.
[33] Goyal, R. N., Gupta, V. K., & Chatterjee, S. (2010). Voltammetric biosensors for the determination of paracetamol at carbon nanotube modified pyrolytic graphite electrode, Sensors and Actuators B, 149, 252–258.
[34] Shahrokhian, S., Kamalzadeh, Z., & Hamzehloei, A. (2013). Electrochemical determination of clozapine on MWCNTs/new coccine doped PPY modified GCE: An experimental design approach, Bioelectrochemistry, 90, 36–43.
[36] Arvand, M., & Ghasempour Shiraz, M. (2012).  Voltammetric determination of clozapine in pharmaceutical formulations and biological fluids using an in situ surfactant-modified carbon ionic liquid electrode, Electroanalysis, 24, 683–690.
[37] Qu, S., Pei, S., Zhang, S., & Song, P. (2013). Preparation of silicate nanotubes and its application for electrochemical sensing of clozapine, Materials Letters, 102–103, 56–58.