INTRODUCTION:

Poverty, population explosion and unhygienic living conditions are the serious concern of human health in developing nations. This has raised the number of peoples susceptible to invasive fungal infections leading to a greater need for effective, well tolerated and easily administered antifungal agents.

Among wide range of antifungal formulations, advent of triazoles has revolutionized the care of patients requiring treatment or prophylaxis for fungal infections¹. Triazoles are the pyrrodiazoles with five-membered, diunsaturated ring system containing three nitrogen atoms in a heterocyclic core and occurs in two possible isomeric forms, 1,2,3 triazoles and 1,2,4 triazoles. Various marketed antifungal therapeutics contain triazole moiety such as fluconazole, isavuconazole, itraconazole, posaconazole, pramiconazole, ravuconazole and voriconazole etc^2-4. Although triazole derived formulations brings benefits to treatment against fungal infection, their prolonged treatment impose adverse reactions in patients like, nausea, vomiting, headache, rash, abdominal pain, diarrhoea, alopecia and rare cases of deaths due to liver failure. Triazole drug analysis is extremely important for quality control, to ensure that the medicine fulfils its antifungal activity effectively without possible complications that could compromise the patient’s health and quality of life^5,6. It is necessary for the routine quality control of pharmaceutical products to employ simple, well-characterized and fully validated analytical methods to yield reliable results that can be satisfactorily interpreted.

Currently marketed formulations of triazole drug in many dosage and forms are categorized according to their doze and administration. Technological advances of formulations containing triazole suggest the need for development and optimization of analytical methods capable of ensuring the quality and quantity of such pharmaceuticals. Significance of analytical methods in quantification of bulk drug materials, intermediates, formulations, impurities and degradation products, their metabolites is very important in relation to human health. For such reasons, developments and strategic modifications in analytical methods for quantification of drugs has received increasing attention in view to quantify the drugs till sensitive levels. In order to serve the purpose, there has been the excessive need to develop a method for standardization of commercial drug formulations for their appropriate administration. European (2002) and American councils of pharmacopeia (2004) has recommended a series of analytical method of quantification of drugs methods based on titrimetry, spectrometry, chromatography, capillary electrophoresis and electrochemistry.

Great efforts have been made to ensure the quality, effectiveness and stability of pharmaceutical products up to the moment of use. The analysis of triazole drugs in biological samples (blood plasma and urine) is usually carried out using high-performance liquid chromatography coupled to fluorimetric detector^7,8, UV/Vis spectroscopy, mass spectrometry⁹ and other highly hyphenated instrument configurations¹⁰. Near infrared spectroscopy and nuclear magnetic resonance methods are relatively sensitive but are costly and not easily accessible. However these methods suffer from some disadvantages including long analysis times, high costs, the requirement for sample pre-treatment and in some cases low sensitivity and selectivity, which make them unsuitable for routine analysis. The limitations associated with such methods leaves electrochemical method, as the best assessable option for triazole drug determination as they include low cost, simple procedures, high sensitivity and short measurement time¹¹.

Nanomaterial based detection systems represents a chief driver towards the adoption of electrochemical methods¹². Over decades, a series of nanomaterials such as CNT, Nanomaterial oxide (NMO) and graphene in various aspect ratios were investigated as electroactive sensing materials for effective, rapid detection and quantification of biological samples^13-21. In this context, carbon derived nanomaterials have received growing preference in development of sensor materials due to their inherent electrical conductivity, chemical stability, strong adsorption capacity, good biocompatibility and high surface area with numerous active sites²². CNT are used to produce nanohybrid for drug delivery to identify the loading and delivery of drugs and antimicrobial performance of implants^23-27. Since CNT base nanohybrids enable functional tenability, novel electrical and catalytic properties that are important for the detection of drugs. Electroactive nanohybrids of CNT and its amine functional analogues doped with NMO have been developed and utilized for estimation of drugs^28-35. Nanohybrid have been incorporated into electrochemical sensor by the surface modification of working electrode and used for investigation of target drug molecules. Three conjugated nitrogen atoms of triazole are responsible for their electro-oxidation-reduction at modified electrode surface in electrolytic media and these electrochemical activities are responsible for signal generation against target drug. Electrochemical response of carbonaceous nanomaterials are much enhanced through transforming them into their metal oxide based nanohybrids, making them suitable as electrode materials for electrochemical sensors. Due to unique properties of CNT/NMO they showed significant enhancement effects on the electrochemical sensing of various drugs. CNT/NMO have widely been used for electrochemical quantification of various drugs like, diclofenac³⁶, cetirizine³⁷, and ibuprofen³⁸, pimozide³⁹, oxymetazoline⁴⁰, dopamine⁴¹, olanzapine⁴², fluorouracile⁴³, benserazide⁴⁴ and triazole drug molecules for electrochemical sensing. The CNT/NMO nanohybrid displays an outstanding synergic effect with triazole molecules that is useful in detecting the triazole drugs (Fig. 1).

Chemistry of nanomaterials is very dynamic and their applications such as estimation of pharmaceutical compounds, disease diagnosis, and other medical applications justify the growing scientific interest in these materials⁴⁵. Particularly, in relation to electrochemical sensors, it was possible to verify that carbonaceous materials are often used in the form of nanohybrids with polymeric materials or metallic nanoparticles in the development of sensors, presenting excellent analytical performance. Sensitivity and selectivity of applied material are the most critical key issues in development of a promising electrode sensor. Biocompatible electrodes sensor has received attention in electrochemical quantification of drug molecules. This has been due to ease of their laboratory scaled fabrication, inexpensive nature, high sensitivity and stability. The efficiency of the electrochemical sensors making a good choice for the determination of drugs and compounds of clinical interest^46.

Development of Electrochemical Drug Sensors:

The design of electrochemical sensors has been done in such a way that they can recognize the plethora of important drugs which, based on the drug structure, often claim specific sensor interface for the realization of their full detection potential. To augment their sensitivity and stability there has been a continuous proposal of Novel electrochemical sensors. They can also lower the limits of detection. Here we summarize the recent advances of the electrochemical sensing of a number of significant pharmaceutical compounds, anti-fungal.

Figure 1: Schematic representation of WE fabrication.

Electrochemical Sensors for Triazole Drugs:

Cutaneous mycosis or dermatophytosis is a common disorder which can affect the epidermis of skin, chest, back upper arms, legs and foot. These infections lead to variety of clinical manifestations that increases cutaneous diseases in military force. Triazole antifungal drugs (Fig.2) are widely used for the treatment of invasive antifungal diseases. Table 1 presented different coating materials for fabrication of modified WEs for electrochemical monitoring of different Triazoles drugs^{48,51,55,58-59.}

a) Fluconazole:

Fluconazole, an antifungal drug is a member of bis-triazole drug, substituted by difluoro phenyl group and propane-2-ol group. Higher drug release rate of Multi layered composites (MLC) rather than pure fluconazole because of high specific surface area (>800m² g^-1) and high porosity (>80%) of silica aerogel. MLC was prepared by adding the hydrophilic and hydrophobic fluconazole drug loaded silica aerogel coated by polyvinyl alcohol (PVA) nano fibers into PVA film as a substrate where PVA nanofibers is used to protect the silica aerogel and to control the rate of drug delivery. For releasing the drug MLC follows non-Fickian mechanism because of rearrangement of macromolecular chain while the drug loaded silica aerogel follows the Fickian mechanism⁴⁷.

Electrochemical behaviour of fluconazole in aqueous medium at Platinum, glassy carbon electrode or carbon paste electrode (CPE), informing a pH dependent oxidation process suppressed at pH below 7.0, anodic peak current increases at pH 8.0 at anodic peak potential _~0.8V, involves the dimerization of triazole because of the formation of a radical cation due to loss of an electron of triazole ring. At CPE increasing concentration of fluconazole is obtained at pH 8.0 and drug is observed at a low detection limit (approx6.3 μg mL^-1), linearity response (R=0.9989) in the range of 48.00 to 250.00μg mL^-1, having Ipa = 5.7×10^-5(mA) × 0.052 (μg mL^-1)⁴⁸.

Fe₃O₄@PA-Ni@Pd/Chitosan nanocomposites modified carbon ionic liquid electrode (CILE) is utilized for the high sensitive determination of fluconazole, reveals the increment of peak current due to subtle electronic properties, high surface area and ion-exchange property of chitosan which increases surface area of fluconazole. The electrochemical response of Fe₃O₄@PA-Ni@Pd-chitosan/CILE in fluconazole is affected by pH of solution and raising the pH of solution until it reaches pH=8, anodic peak current of fluconazole increases. In the developed fluconazole sensor the concentration of fluconazole is directly proportional to peak current in the linear range of 0.01 to 3.5 nM and validated by determination of fluconazole in tablets, plasma and human urine sample⁴⁹.

Figure 2: Molecular structures of a triazole antifungal drugs.

b) Itraconazole:

Itraconazole (ITZ), an antifungal drug and Imatinib (IMA) are detected by electrochemical sensor based on ZnO-NiO/MWCNT-COOH modified glassy carbon electrode (GCE) having reproductivity, good selectivity and sensitivity⁵⁰. Prepared material is characterized by Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, X- Ray Diffraction, Cyclic Voltammetry (CV) and Raman spectroscopy. The electrochemical behavior of ITZ and IMA in potential range 0.6V to 1.3V were studied by Differential pulse voltammetry (DPV) in B-R buffer solution which investigated the linear relationship of the concentration (range from 0.025 to 2.2μm) for ITZ and concentration (range from 0.015 to 2.0μM) for IMA with the oxidation peak current and in B-R buffer pH 4.5 the maximum current density is observed. ITZ having low detection limit 4.1 nm, sensitivity 2.64μA μM^-1 cM^-2 and for IMA low detection limit 2.4nM, sensitivity 9.64μA μM^-1cM^-2. The prepared sensor was successfully worked in human serum and urine sample for detecting IMA and ITZ⁵¹.

ITZ electrochemical behavior was sensed by the multiwalled carbon nano tubes (MWCNT) modified carbon paste electrode (CPE), investigated the determination of antifungal ITZ in drugs bulk powder, human urine sample, quantity control laboratories and dosage form. In MWCNT/CPE the cyclic voltammetry study of ITZ studied at 0-1.1V potential window range and 450mV/s scan rate, shows a sharp anodic peak potential at 0.680V. DPV calibration curve of ITZ at MWCNT/CPE gives anodic peak potential at 745mV/s, within the concentration range 1.55-44.68μg/ml (R²=0.999) the height of peak and concentration are linearly related to each other with 0.51μg/ml limit of detection and 1.55μg/ml limit of quantification^52-54.

c) Letrozole:

Letrozole, 4,4’((1H-1,2,4-triazole-1yl) methylene) dibenzonitrile is a non-steroidal aromatase inhibitor drug treated the hormonally responsive breast cancer after surgery. CV at gold ultra microelectrode during the flow injection of 50μL of 3.0×10^-6 mol/L letrozole into 0.05mol/L of H₃PO₄eluent, which shows the change in current peak at reduction and oxidation potential region due to the inhibition of surface process, hence the concentration of letrozole can be determined in trace amount from this method by monitoring the current changes and signal to noise ratio has enhanced by applying fast fourier transform. To achieve the maximum sensitivity of drug some experimental parameters such as eluent pH, sweep rate, accumulation time and potential were also optimized and the performance was validated by linear concentration range 0.2-0.0001μmol/L (r=0.9975), 0.08nmol/L limit of detection and 0.015nmol/L limit of quantification⁵⁵.

Developed the ion exchange mechanism based two types of potentiometric electrode, PVC membrane and nano-composites carbon paste electrode (CPE) for sensing the letrozole and best performance of sensors were achieved by membrane composition of 30% PVC, 65%nitrobenzene and 5% ion-pair and CPE composition of 20% ion-pair, 20% paraffin oil, 5% multi-walled carbon nano tube and 55% graphite powder. A linear response was calculated for letrozole in concentration range 5×10^-6-1×10^-2M with 3×10^-6detection limit and 1×10^-6-1×10^-2M with 1×10^-6M detection limit for PVC membrane and CPE respectively⁵⁶.

d) Ketoconazole:

Developed a high selective, good sensitive and stable electrochemical sensor based on gold nanoparticle modified carbon paste electrode (AuNPs/CPE) for determination of ketoconazole (KCZ). This was prepared by mixing graphite powder with gold nanoparticles and paraffin oil, the electrochemical performance were investigated from 2.0-7.0 pH by voltammteric technique. The CV of AuNPs/CPE at pH range 3-6 shows two anodic peak potential at 0.697 and 0.983V because of imidazole group oxidation and piperazine group oxidation respectively. The cathodic peak potential was obtained at 0.612V due to deprotonation of imidazole group. Square Wave Voltammetry (SWV) were observed at pH 4 of 0.5M phosphate buffer solution, a linear relationship was obtained between oxidation current and concentration of KCZ in range of 1.00-80.00 μmol L^-1 with correlation coefficient (r²=0.998) and 0.1 μmol L^-1 limit of detection. The developed sensor effectively worked for the quantification of KCZ in pharmaceutical formulation and cosmetics⁵⁷.

KCZ antifungal drugs were determined by SWV and boron-doped diamond electrode (BDD). The CV study of KCZ at BDD electrode was recorded at 100 mV s^-1 scan rate and 1.8-6.5 pH range, which achieve an oxidation peak and reduction peak in the potential window of 0.45-0.75 V. The quantitative determination of KCZ was performed by SWV in NH₃-NH₄Cl buffer pH 9.42, gives a linear relationship between current and concentration of KCZ in the range of 2.87×10^-7 to 3.13×10^-6 mol L^-1 with 8.29×10^-8 mol L^-1 and 2.51×10^-7 limit of detection and quantification respectively⁵⁸.

CONCLUSION:

Due to the technological advancements that happened in the past decade, it has become possible to design and manufacture a variety of sensors. These nanomaterials-based sensors have a plethora of applications in analytical chemistry. One of the applications where these sensors are helpful is in the detection of drugs, detection of which is very crucial and important as they are responsible for various biological processes. The present review paper mainly holds the description of sensors based on nanomaterials derived from carbon. These include carbon nanofibers, carbon nanotubes (CNTs), fullerenes, carbon black, etc. All these nanomaterials have high electrical conductibility, good electrocatalytic properties, and the existence of plenty of active sites. These properties provide features such as increased accuracy, sensitivity, and selectivity of electrochemical sensors. The focus of this review is on nanomaterials bases main electrochemical sensors used for the detection of triazole drugs. Triazole antifungals are treated as frontline drugs when it comes to the treatment and prophylaxis of many systematic mycoses. The main advantage carried by these nanomaterials-based electrochemical sensors is in the detection of the triazole drugs with high accuracy, high sensitivity, and ample selectivity. This all makes it the right choice for clinical analysis, in diagnosis research, and also in quality control.

CONFLICT OF INTEREST:

No potential conflict of interest was reported by the author.

REFERENCES:

1. Lass-Flörl C. Triazole Antifungal Agents in Invasive Fungal Infections. Drugs. 2011 Dec; 71(18):2405-19. doi.org/10.2165/11596540-000000000-00000

2. Watt K, Manzoni P, Cohen-Wolkowiez M, Rizzollo S, Boano E, Jacqz-Aigrain E, K Benjamin D. Triazole use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole. Current Drug Metabolism. 2013 Feb 1; 14(2):193-202. doi.org/10.2174/138920013804870583

3. Neofytos D, Avdic E, Magiorakos Ap. Clinical Safety and Tolerability Issues in use of Triazole Derivatives in Management of Fungal Infections. Drug, Healthcare and Patient Safety. 2010; 2:27. doi: 10.2147/Dhps.S6321

4. Peyton LR, Gallagher S, Hashemzadeh M. Triazole Antifungals: A Review. Drugs Today. 2015 Dec 1; 51(12):705-18.

5. Martínez-Matías N, Rodríguez-Medina JR. Fundamental Concepts of Azole Compounds and Triazole Antifungals: A Beginner’s Review. Puerto Rico Health Sciences Journal. 2018 March; 37(1):3.

6. Shalini K, Kumar N, Drabu S, Sharma PK. Advances in Synthetic Approach to and Antifungal Activity of Triazoles. Beilstein Journal of Organic Chemistry. 2011May 25; 7(1):668-77. doi.Org/10.3762/Bjoc.7.79

7. Srivatsan V, Dasgupta AK, Kale P, Datla RR, Soni D. Patel M, Patel R, Mavadhiya C. Simultaneous Determination of Itraconazole and Hydroxyitraconazole in Human Plasma by High-Performance Liquid Chromatography. Journal of Chromatography A. 2004 March 26; 1031(1-2):307-13. doi.Org/10.1016/J.Chroma.2003.11.061

8. Michael C, Teichert J, Preiss R. Determination of Voriconazole in Human Plasma and Saliva using High-Performance Liquid Chromatography with Fluorescence Detection. Journal of Chromatography B. 2008 April 1; 865(1-2):74-80. doi.Org/10.1016/J.Jchromb.2008.02.009

9. Rhim SY, Park JH, Park YS, Kim DS, Lee MH, Shaw LM, Kang JS. A Sensitive Validated LC-MS/MS Method for Quantification of Itraconazole in Human Plasma for Pharmacokinetic and Bioequivalence Study in 24 Korean Volunteers. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2009 Feb 1; 64(2):71-5. doi.Org/10.1691/Ph.2009.7795

10. BrüGgemann RJ, Touw DJ, Aarnoutse RE, Verweij PE, Burger DM. International Interlaboratory Proficiency Testing Program for Measurement of Azole Antifungal Plasma Concentrations. Antimicrobial Agents and Chemotherapy. 2009 Jan; 53(1):303-5. doi.Org/10.1128/AAC.00901-08

11. Stradiotto NR, Yamanaka H, Zanoni MV. Electrochemical Sensors: A Powerful Tool in Analytical Chemistry. 2003; 159-173. doi.Org/10.1590/S0103-50532003000200003

12. Tonelli D, Scavetta E, Gualandi I. Electrochemical Deposition of Nanomaterials for Electrochemical Sensing. Sensors. 2019 Jan; 19(5):1186. doi.Org/10.3390/S19051186

13. Ghalkhani M, Ghorbani-Bidkorbeh F. Development of Carbon Nanostructured Based Electrochemical Sensors for Pharmaceutical Analysis. Iranian Journal of Pharmaceutical Research. 2019; 18(2):658. doi: 10.22037/Ijpr.2019.1100645

14. Vidhi RPatel, Dhrubo Jyoti Sen, CN Patel. Synthesis, Purification and Identification of Carbon Nanotubes: A Review. Research Journal of Science and Technology. 2011; 3(3): 137-150.

15. Ishraq MHassan, Duha MALatif. The Effect of MGO Nanoparticles on Structure and optical Properties of PVA-PAAm Blend. Research Journal of Science and Technology. 2019; 12(6): 2768-2771. doi: 10.5958/0974-360X.2019.00464.5

16. Madhu Yadav, Pankaj Baboo, Nisha Gupta, Vandana Arora. Composition and Characterisation of Argent Nanoparticles and Argent Bionanocomposities. Asian Journal of Research in Chemistry. 2018; 11(5):811-814. doi: 10.5958/0974-4150.2018.00143.8

17. Harkamal Preet Singh, Amit Chauhan, Prashant Jindal. Fabrication of Al2024/MWCNT Composite. Research Journal of Science and Technology. 2017; 8(3): 191-194. doi: 10.5958/2321-581X.2017.00031.9

18. Sunil HGanatra, Sneha DKhobragade, Anushree SUjjankar, Chudaman DPourkar. Studies of Thermal Conductivity in Carbon Nanotubes Using Simulation. Asian Journal of Research in Chemistry. 2012 April; 5(4): 500-503.

19. Fasiuddin Arif Mohammad, Kishore Rapolu, Shanthan Kumar Valugonda, Srinivas Balusu. Optimization of Cuprous Oxide Nanocrystals Deposition on Multiwalled Carbon Nanotubes. Asian Journal of Research in Chemistry. 2012 January; 5(1): 116-124.

20. D. Jesudurai, RMonika. Preparation of Silver Nanoparticles from Bael (Aegle marmelos) Leaves Extract and their Doping with Multiwalled Carbon Nanotubes for Antibacterial Utility. Research Journal of Pharmacy and Technology 2020; 13(6):2653-2657. doi: 10.5958/0974-360X.2020.00471.0

21. Krishnat DDhekale, Ravindra NKamble. Development of cefdinir loaded Functionalized carbon Nanotubes dry powder Inhaler for the Treatment of cystic Fibrosis. Research Journal of Pharmacy and Technology. 2021; 14(7):3839-5. doi: 10.52711/0974-360X.2021.00666

22. Cha C, Shin SR, Annabi N, Dokmeci MR, Khademhosseini A. Carbon-Based Nanomaterials: Multifunctional Materials for Biomedical Engineering. American Chemical Society Nano. 2013 April 23; 7(4):2891-7. doi.Org/10.1021/Nn401196a

23. Adhikari BR, Govindhan M, Chen A. Carbon Nanomaterials based Electrochemical Sensors/Biosensors for the Sensitive Detection of Pharmaceutical and Biological Compounds. Sensors. 2015 Sep; 15(9):22490-508. doi.Org/10.3390/S150922490

24. Zhao Q, Gan Z, Zhuang Q. Electrochemical Sensors based on Carbon Nanotubes. Electroanalysis: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis. 2002 Dec; 14(23):1609-13.doi.Org/10.1002/Elan.200290000

25. Wang J. Carbon‐Nanotube based Electrochemical Biosensors: A Review. Electroanalysis: An International Journal Devoted to Fundamental And Practical Aspects of Electroanalysis. 2005 Jan; 17(1):7-14. doi.Org/10.1002/Elan.200403113

26. Hu C, Hu S. Carbon Nanotube-Based Electrochemical Sensors: Principles and Applications in Biomedical Systems. Journal of Sensors. 2009 Nov. doi.Org/10.1155/2009/187615

27. Wernik JM, Meguid SA. Recent Developments in Multifunctional Nanocomposites Using Carbon Nanotubes. Applied Mechanics Reviews. 2010 Sep 1 ;63(5). doi.Org/10.1115/1.4003503

28. Aftab S, Kurbanoglu S, Ozcelikay G, Shah A, Ozkan SA. NH2‐Functionalized Multi Walled Carbon Nanotubes Decorated with Zno Nanoparticles and Graphene Quantum Dots for Sensitive Assay of Pimozide. Electroanalysis. 2019 Jun; 31(6):1083-94. doi.Org/10.1002/Elan.201800788

29. Munir A, Bozal-Palabiyik B, Khan A, Shah A, Uslu B. A Novel Electrochemical Method for the Detection of Oxymetazoline Drug based on Mwcnts and Tio2 Nanoparticles. Journal of Electroanalytical Chemistry. 2019; 844:58-65. doi.Org/10.1016/J.Jelechem.2019.05.017

30. Fayemi OE, Adekunle AS, Ebenso EE. Metal Oxide Nanoparticles/Multi-Walled Carbon Nanotube Nanocomposite Modified Electrode for the Detection of Dopamine: Comparative Electrochemical Study. Journal of Biosensor and Bioelectronics. 2015; 6:190-204. doi: 10.4172/2155-6210.1000190

31. Arvand M, Palizkar B. Development of A Modified Electrode with Amine-Functionalized Tio2/Multi-Walled Carbon Nanotubes Nanocomposite for Electrochemical Sensing of the a typical Neuroleptic Drug Olanzapine. Materials Science and Engineering: C. 2013 Dec 1; 33(8):4876-83. doi.Org/10.1016/J.Msec.2013.08.002

32. Shojaei AF, Tabatabaeian K, Shakeri S, Karimi F. A Novel 5-Fluorouracile Anticancer Drug Sensor based on Znfe2o4 Magnetic Nanoparticles Ionic Liquids Carbon Paste Electrode. Sensors and Actuators B: Chemical. 2016 July 1; 230:607-14. doi.Org/10.1016/J.Snb.2016.02.082

33. Dange YD, Honmane SM, Patil PA, Gaikwad UT, Jadge DR. Nanotechnology, Nanodevice Drug Delivery System: A Review. Asian Journal of Pharmaceutical Sciences. 2017; 7(2): 63-71. doi: 10.5958/2231-5713.2017.00010.1

34. S Viswanathan, NVinoth Kumar, Prathiba Srinivasan, SPrabhu. Nanoparticle-Mediated Drug Delivery Systems. Research Journal of Applied Sciences, Engineering and Technology. 2013 Oct.-Dec; 4(4): 295-299.

35. Syed Zia ul Quasim, Mohd Irfan Ali, Syed Irfan, Abdul Naveed. Advances in Drug Delivery System: Carbon Nanotubes. Research Journal of Pharmacy and Technology. 2013 Feb; 6(2): 125-129.

36. Eteya MM, Rounaghi GH, Deiminiat B. Fabrication of A New Electrochemical Sensor Based on Aupt Bimetallic Nanoparticles Decorated Multi-Walled Carbon Nanotubes for Determination of Diclofenac. Microchemical Journal. 2019 Jan 1; 144:254-60. doi.Org/10.1016/J.Microc.2018.09.009

37. Shetti NP, Malode SJ, Nayak DS, Aminabhavi TM, Reddy KR. Nanostructured Silver Doped Tio2/Cnts Hybrid as an Efficient Electrochemical Sensor for Detection of Anti-Inflammatory Drug, Cetirizine. Microchemical Journal. 2019 March 1; 150:104124. doi.Org/10.1016/J.Microc.2019.104124

38. Montes RH, Lima AP, Cunha RR, Guedes TJ, Dos Santos WT, Nossol E, Richter EM, Munoz RA. Size Effects of Multi-Walled Carbon Nanotubes on The Electrochemical Oxidation of Propionic Acid Derivative Drugs: Ibuprofen and Naproxen. Journal of Electroanalytical Chemistry. 2016 Aug 15; 775:342-9. doi.Org/10.1016/J.Jelechem.2016.06.026

39. Aftab S, Kurbanoglu S, Ozcelikay G, Shah A, Ozkan SA. NH2‐Functionalized Multi Walled Carbon Nanotubes Decorated with Zno Nanoparticles and Graphene Quantum Dots for Sensitive Assay of Pimozide. Electroanalysis. 2019 Jun; 31(6):1083-94. doi.Org/10.1002/Elan.201800788

40. Munir A, Bozal-Palabiyik B, Khan A, Shah A, Uslu B. A Novel Electrochemical Method for the Detection of Oxymetazoline Drug based on Mwcnts and Tio2 Nanoparticles. Journal of Electroanalytical Chemistry. 2019 July 1; 844:58-65. doi.Org/10.1016/J.Jelechem.2019.05.017

41. Rajaei M, Foroughi MM, Jahani S, Zandi MS, Nadiki HH. Sensitive Detection of Morphine in the Presence of Dopamine with La3+ Doped Fern-Like Cuo Nanoleaves/Mwcnts modified Carbon Paste Electrode. Journal of Molecular Liquids. 2019 July 15; 284:462-72. doi.Org/10.1016/J.Molliq.2019.03.135

42. Arvand M, Palizkar B. Development of A Modified Electrode with Amine-Functionalized Tio2/Multi-Walled Carbon Nanotubes Nanocomposite for Electrochemical Sensing of the a typical Neuroleptic Drug Olanzapine. Materials Science and Engineering C. 2013 Dec 1; 33(8):4876-83. doi.Org/10.1016/J.Msec.2013.08.002

43. Shojaei AF, Tabatabaeian K, Shakeri S, Karimi F. A Novel 5-Fluorouracile Anticancer Drug Sensor based on Znfe2o4 Magnetic Nanoparticles Ionic Liquids Carbon Paste Electrode. Sensors and Actuators B: Chemical. 2016 July 1; 230:607-14. doi.Org/10.1016/J.Snb.2016.02.082

44. Rahmanifar E, Yoosefian M, Karimi-Maleh H. Application of Cdo/Swcnts Nanocomposite Ionic Liquids Carbon Paste Electrode as a Voltammetric Sensor for Determination of Benserazide. Current Analytical Chemistry. 2017 Feb 1; 13(1):46-51.

45. Ajayan PM, Zhou OZ. Applications of Carbon Nanotubes. Carbon Nanotubes. 2001:391-425. doi.Org/10.1007/3-540-39947-X_14

46. Tonelli D, Scavetta E, Gualandi I. Electrochemical Deposition of Nanomaterials for Electrochemical Sensing. Sensors. 2019 Jan; 19(5):1186. doi.Org/10.3390/S19051186

47. Afrashi M, Semnani D, Talebi Z, Dehghan P, Maheronnaghsh M. Novel Multi-Layer Silica Aerogel/PVA Composite for Controlled Drug Delivery. Materials Research Express. 2019 July 17; 6(9):095408. doi.Org/10.1088/2053-1591/Ab3097

48. Gil ÉDS, Cordeiro DD, Matias AE, Serrano SH. Electrochemical Behavior and Determination of Fluconazole. Journal of the Brazilian Chemical Society. 2011; 22(4), 767-771.

49. Zad ZR, Davarani SS, Taheri A, Bide Y. A Yolk Shell Fe3O4@ PA-Ni@ Pd/Chitosan Nanocomposite-Modified Carbon Ionic Liquid Electrode as a New Sensor for the Sensitive Determination of Fluconazole in Pharmaceutical Preparations and Biological Fluids. Journal of Molecular Liquids. 2018 March 1; 253:233-doi.Org/10.1016/J.Molliq.2018.01.019

50. Bailey EM, Krakovsky DJ, Rybak MJ. The Triazole Antifungal Agents: A Review of Itraconazole and Fluconazole. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 1990 March 4; 10(2):146-53. doi.Org/10.1002/J.1875-9114.1990.Tb02561.X

51. Chen H, Luo K, Li K. A Facile Electrochemical Sensor based on Nio-Zno/MWCNT-COOH modified GCE for Simultaneous Quantification of Imatinib and Itraconazole. Journal of the Electrochemical Society. 2019 May 16; 166(8):697. doi.Org/10.1149/2.1071908jes

52. Sultan MA, Attia AK, El-Alamin MM, Atia MA. The Novel Use of Multiwalled Carbon Nanotubes-based Sensors for Voltammetric Determination of Itraconazole: Application to Pharmaceutical Dosage form and Biological Samples through Spiked Urine Sample. World Journal of Pharmacy and Pharmaceutical Sciences. 2016 June 20; 5:93-108.

53. Srivatsan V, Dasgupta AK, Kale P, Datla RR, Soni D, Patel M, Patel R, Mavadhiya C. Simultaneous Determination of Itraconazole and Hydroxyitraconazole in Human Plasma by High-Performance Liquid Chromatography. Journal of Chromatography A. 2004 March 26; 1031(1-2):307-13. doi.Org/10.1016/J.Chroma.2003.11.061

54. Jaruratanasirikul S, Sriwiriyajan S. Pharmacokinetic Study of the Interaction Between Itraconazole and Nevirapine. European Journal of Clinical Pharmacology. 2007 May; 63(5):451-6. doi.Org/10.1007/S00228-007-0280-X

55. Norouzi P, Ganjali MR, Qomi M, Nemati Kharat A, Zamani HA. Monitoring of Anti Cancer Drug Letrozole by Fast Fourier Transform Continuous Cyclic Voltammetry at Gold Microelectrode. Chinese Journal of Chemistry. 2010 July; 28(7):1133-9. doi.Org/10.1002/Cjoc.201090197

56. Ganjali MR, Karimi A, Norouzi P. Letrozole Potentiometric PVC Membrane and Nano-Composite Carbon Paste Electrodes. International Journal of Electrochemistry 2012 April 1; 7:3681-92.

57. Saleh TA, Alaqad KM, Rahim A. Electrochemical Sensor for the Determination of Ketoconazole based on Gold Nanoparticles Modified Carbon Paste Electrode. Journal of Molecular Liquids. 2018 April 15; 256:39-48. doi.Org/10.1016/J.Molliq.2018.02.006

58. Mielech-Łukasiewicz K, Rogińska K. Voltammetric Determination of Antifungal Agents in Pharmaceuticals and Cosmetics Using Boron-Doped Diamond Electrodes. Analytical Methods. 2014; 6(19):7912-22. doi.Org/10.1039/C4AY01421A

59. Hassan RY, Sultan MA, El‐Alamin MM, Atia MA, Aboul‐Enein HY. A Disposable Carbon Nanotubes‐Screen Printed Electrode (Cnts‐SPE) for Determination of the Antifungal Agent Posaconazole in Biological Samples. Electroanalysis. 2017 March; 29(3):843-9. doi.Org/10.1002/Elan.201600621

Received on 26.07.2021 Modified on 18.02.2022

Research J. Pharm. and Tech 2023; 16(2):969-974.

DOI: 10.52711/0974-360X.2023.00162

S. No.	Drug Name	Working Electrode	Characterization	Limit of detection	pH range	References
1.	Fluconazole	GCE or CPE	CV, DPV	6.3 μg /mL	6-8	[48]
2.	Posaconazole	MWCNTs/CPE	CV	11 ng/ml	3	[59]
3.	Itraconazole	MWCNTs/CPE	CV	0.51 µg/m	5	[51]
4.	Letrozole	Gold electrode	CV	0.08 nmol/L	2.0	[55]
5.	Ketoconazole	Boron doped diamond electrode	SWV	8.29 × 10^-8mol/L	1.8 to 6.5	[58]