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Journals / Journal of the Turkish Chemical Society Section A: Chemistry / 2026 / Volume: 2026 Issue: 2

Electrochemical Determination of Tricyclic Antidepressants: Mechanisms, Sensor Technologies, and Analytical Trends

Elif Mollahasanoğlu(KARADENIZ TECHNICAL UNIVERSITY, FACULTY OF PHARMACY)0000-0003-4092-3195
Fatma Ağın(KARADENIZ TECHNICAL UNIVERSITY, FACULTY OF PHARMACY)0000-0002-6973-4323
Pages
—
Publication Date
2026-07-31
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Additionally, miniaturization, biocompatibility integration, sustainable sensor design, and machine learning-enhanced voltammetric data analysis have been explored to establish a roadmap for the future clinical translation of the TCA's electrochemical detection approach.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Tricyclic antidepressants (TCAs) constitute an important class of psychotropic drugs widely prescribed for major depressive and anxiety disorders.
📊
Key Findings & Data:Owing to their narrow therapeutic range and significant toxicity at elevated plasma concentrations, the precise quantification of TCAs in pharmaceutical formulations and biological fluids is essential for therapeutic drug monitoring.
💡
Conclusion & Impact:Additionally, miniaturization, biocompatibility integration, sustainable sensor design, and machine learning-enhanced voltammetric data analysis have been explored to establish a roadmap for the future clinical translation of the TCA's electrochemical detection approach.
🔬Design:Review & Systematic Survey
📍Scope:2025 Verileri
⚙️Variables:Electrochemical sensors · Modified electrodes · Personalized medicine

Abstract

Tricyclic antidepressants (TCAs) constitute an important class of psychotropic drugs widely prescribed for major depressive and anxiety disorders. Owing to their narrow therapeutic range and significant toxicity at elevated plasma concentrations, the precise quantification of TCAs in pharmaceutical formulations and biological fluids is essential for therapeutic drug monitoring. Spanning the period from the first electrochemical reports in 1984 to the most recent developments in 2025, this review provides a comprehensive overview of the electrochemical behavior of TCAs, emphasizing structure–reactivity relationships, oxidation mechanisms, and the evolution of electrode materials used for their voltammetric detection. Particular attention is given to advances in noble-metal, carbon-based, polymer-modified, nanocomposite, molecularly imprinted, and biofunctionalized electrodes, as well as emerging hybrid biosensing and microextraction-voltammetry platforms. The review further examines analytical performance relative to conventional techniques and highlights applications in pharmaceutical and biological matrices. Additionally, miniaturization, biocompatibility integration, sustainable sensor design, and machine learning-enhanced voltammetric data analysis have been explored to establish a roadmap for the future clinical translation of the TCA's electrochemical detection approach.

🔖

Cite This Article

Mollahasanoğlu, E., Ağın, F. (2026). Electrochemical Determination of Tricyclic Antidepressants: Mechanisms, Sensor Technologies, and Analytical Trends. Journal of the Turkish Chemical Society Section A: Chemistry, Volume: 2026 Issue: 2. https://doi.org/10.18596/jotcsa.1945759

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References (98)

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  31. Xu X, Zhou G, Li H, Liu Q, Zhang S, Kong J. A novel molecularly imprinted sensor for selectively probing imipramine created on ITO electrodes modified by Au nanoparticles. Talanta. 2009 Apr 15;78(1):26–32. Available from:.
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  53. Gao K, Oruc EB, Koparal B. Pharmacological monotherapy for depressive disorders: Current and future—A narrative review. Medicina. 2025 Mar 21;61(4):558. Available from:.
  54. Martin DM, Jones J, Costantino A, Kaushik S, Gold MS. Characteristics and laboratory testing standards for drugs of abuse. In: England JD, editor. Reference Module in Neuroscience and Biobehavioral Psychology. Elsevier; 2023. p. 277–302. Available from:.
  55. Marasine NR, Sankhi S, Lamichhane R, Marasini NR, Dangi NB. Use of antidepressants among patients diagnosed withdepression: A scoping review. Iannotti F, editor. Biomed Res Int. 2021 Jan 15;2021(1):6699028. Available from:.
  56. Mercolini L. Editorial: Advances in therapeutic drug monitoring of psychiatric subjects: Analytical strategies and clinical approaches. Front Psychiatry. 2022 Oct 18;13:1056380. Available from:.
  57. Burke MJ, Preskorn SH. Therapeutic drug monitoring of antidepressants. Clin Pharmacokinet. 1999;37(2):147–65. Available from:.
  58. Uddin MN, Samanidou VF, Papadoyannis IN. HPLC method for simultaneous determination of 1,4-benzodiazepines and tricyclic antidepressants in pharmaceutical formulations and saliva—A useful tool in medicinal chemistry. J Liq Chromatogr Relat Technol. 2009 Apr 28;32(10):1475–504. Available from:.
  59. Berlato DG, Bezerra Pacheco AL, Ugalde GA, Reginato FZ, Saldanha G de A, Oliveira TF de, et al. Dispersive liquid-liquid microextraction (DLLME) for determination of tricyclic antidepressants in whole blood and plasma samples and analysis by liquid chromatography with diode array detector (LC-DAD). Toxicol Mech Methods. 2024 Feb 12;34(2):189–202. Available from:.
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  61. Caldevilla R, Morais SL, Cruz A, Delerue-Matos C, Moreira F, Pacheco JG, et al. Electrochemical chemically based sensors and emerging enzymatic biosensors for antidepressant drug detection: A review. Int J Mol Sci. 2023 May 9;24(10):8480. Available from:.
  62. Li S, Zhang H, Zhu M, Kuang Z, Li X, Xu F, et al. Electrochemical biosensors for whole blood analysis: Recent progress, challenges, and future perspectives. Chem Rev. 2023 Jun 28;123(12):7953–8039. Available from:.
  63. Rodrigues ESB, de Macêdo IYL, da Silva Lima LL, Thomaz DV, da Cunha CEP, Teles de Oliveira M, et al. Electrochemical characterization of central action tricyclic drugs by voltammetric techniques and density functional theory calculations. Pharmaceuticals. 2019 Aug 1;12(3):116. Available from:.
  64. Smajdor J, Fendrych K, Górska-Ratusznik A. Carbon materials in voltammetry: An overview of versatile platforms for antidepressant drug detection. Micromachines. 2025 Mar 31;16(4):423. Available from:.
  65. Teymourian H, Parrilla M, Sempionatto JR, Montiel NF, Barfidokht A, Van Echelpoel R, et al. Wearable electrochemical sensors for the monitoring and screening of drugs. ACS Sensors. 2020 Sep 25;5(9):2679–700. Available from:.
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  69. Souri Z, Masoudi Khoram M, Nematollahi D, Mazloum-Ardakani M, Alizadeh H. A green protocol for the electrochemical synthesis of a fluorescent dye with antibacterial activity from imipramine oxidation. Sci Rep. 2022 Mar 22;12(1):4921. Available from:.
  70. Smotkin ES, Martin GB, Rechnitz GA. Electrochemical determination of tricyclic antidepressants. Anal Lett. 1991 May 23;24(5):797–808. Available from:.
  71. Farjami F, Fasihi F, Alimohammadi F, Moradi SE. Electrochemical behavior and highly sensitive voltammetric determination of doxepin in pharmaceutical preparations and blood serum using carbon ionic liquid electrode. Iran J Pharm Res IJPR. 2019;18(1):91–101. Available from:.
  72. Guzinski M, Lindner E, Pendley B, Chaum E. Electrochemical sensor for tricyclic antidepressants with low nanomolar detection limit: Quantitative determination of amitriptyline and nortriptyline in blood. Talanta. 2022 Mar;239:123072. Available from:.
  73. Malode SJ, Ali Alshehri M, Shetti NP. Nanomaterial-based electrochemical sensors for the detection of pharmaceutical drugs. Chemosensors. 2024 Nov 11;12(11):234. Available from:.
  74. Kipkorir E, Kimani O. Electrochemical sensing of pharmaceutical pollutants using modified glassy carbon electrodes with nanostructures: A review. Inorg Chem Commun. 2025 Sep;179:114827. Available from:.
  75. Yamuna A, Chen TW, Chen SM, Al-Mohaimeed AM, Al-onazi WA, Elshikh MS. Selective electrochemical detection of antidepressant drug imipramine in blood serum and urine samples using an antimony telluride-graphite nanofiber electrode. Microchim Acta. 2021 Feb 28;188(2):60. Available from:.
  76. Henrique Duarte E, dos Santos WP, Fantinato Hudari F, Bott Neto JL, Romão Sartori E, Dall׳Antonia LH, et al. A highly improved method for sensitive determination of amitriptyline in pharmaceutical formulations using an unmodified carbon nanotube electrode in the presence of sulfuric acid. Talanta. 2014 Sep;127:26–32. Available from:.
  77. Oliveira SN, Ribeiro FWP, Sousa CP, Soares JES, Suffredini HB, Becker H, et al. Imipramine sensing in pharmaceutical formulations using boron-doped diamond electrode. J Electroanal Chem. 2017 Mar;788:118–24. Available from:.
  78. Ghasemi L, Jahani S, Ghazizadeh M, Foroughi MM. Simultaneous determination of amitriptyline and venlafaxine using a novel voltammetric sensor of carbon paste electrode modified with octahedral Pd2+-doped Co3O4 composite. Mater Chem Phys. 2023 Feb;296:127176. Available from:.
  79. Lakshmi A, Vedhi C. Synthesis and characterization of poly (3-hexylthiophene) and used as modified electrode for determination of antidepressants in pharmaceutical formulations and urine samples. J Electrochem Soc. 2013 Feb 26;160(4):H252–7. Available from:.
  80. Xu X, Zhou G, Li H, Liu Q, Zhang S, Kong J. A novel molecularly imprinted sensor for selectively probing imipramine created on ITO electrodes modified by Au nanoparticles. Talanta. 2009 Apr 15;78(1):26–32. Available from:.
  81. Eslami E, Farjami F, Aberoomand Azar P, Saber Tehrani M. Adsorptive stripping voltammetric determination of imipramine and amitriptiline at a nanoclay composite carbon ionic liquid electrode. Electroanalysis. 2014 Feb;26(2):424–31. Available from:.
  82. Marco JP, Borges KB, Tarley CRT, Ribeiro ES, Pereira AC. Development and application of an electrochemical biosensor based on carbon paste and silica modified with niobium oxide, alumina and DNA (SiO2/Al2O3/Nb2O5/DNA) for amitriptyline determination. J Electroanal Chem. 2013 Sep;704:159–68. Available from:.
  83. Saraji M, Farajmand B, Ensafi AA, Allafchian AR, Zare ZM. Combined hollow fiber-based liquid–liquid–liquid microextraction and in-situ differential pulse voltammetry to improve selectivity, sensitivity, and interference elimination in electrochemical analysis. Talanta. 2010 Sep 15;82(4):1588–93. Available from:.
  84. Hussein W, Bishop E, Waqar D. Electro-analysis of the drugs in solid dosage form at platinum and gold electrodes. Pak J Pharm Sci. 2013;26(5):977–84. Available from:.
  85. Turhan E, Uslu B. Electroanalytical determination of opipramol in pharmaceutical preparations and biological fluids. Anal Lett. 2008 Jul 24;41(11):2013–32. Available from:.
  86. Atty SA, Sedik GA, Morsy FA, Naguib DM, Zaazaa HE. A novel sensor aluminum silicate modified carbon paste electrode for determination of anti-depressant dothiepin HCl in pharmaceutical formulation and biological fluids. Microchem J. 2019 Jul;148:725–34. Available from:.
  87. Madej M, Fendrych K, Porada R, Flacha M, Kochana J, Baś B. Application of Fe(III)-exchanged clinoptilolite/graphite nanocomposite for electrochemical sensing of amitriptyline. Microchem J. 2021 Jan;160:105648. Available from:.
  88. Sanghavi BJ, Srivastava AK. Adsorptive stripping voltammetric determination of imipramine, trimipramine and desipramine employing titanium dioxide nanoparticles and an Amberlite XAD-2 modified glassy carbon paste electrode. Analyst. 2013;138(5):1395–404. Available from:.
  89. Zad ZR, Davarani SSH, Taheri AR, Bide Y. Highly selective determination of amitriptyline using Nafion-AuNPs@branched polyethyleneimine-derived carbon hollow spheres in pharmaceutical drugs and biological fluids. Biosens Bioelectron. 2016 Dec;86:616–22. Available from:.
  90. Khan AAP. Electrocatalytic behavior and determination of amitriptyline drug with MWCNT@Celllulose composite modified glassy carbon electrode. Materials (Basel). 2020 Apr 6;13(7):1708. Available from:.
  91. Cincotto FH, Carvalho DAS, Canevari TC, Toma HE, Fatibello-Filho O, Moraes FC. A nano-magnetic electrochemical sensor for the determination of mood disorder related substances. RSC Adv. 2018;8(25):14040–7. Available from:.
  92. Fendrych K. Synergistic Fe(III)-clinoptilolite and multi-walled carbon nanotube composite for enhanced voltammetric determination of opipramol in complex matrices. J Electrochem Soc. 2025 Oct 1;172(10):107508. Available from:.
  93. Farjami F, Fasihi F, Moradi SE, Darvishi T, Shafiee GH. Electrochemical oxidation of nortriptyline and its voltammetric sensing at a carbon ionic liquid electrode. J Anal Chem. 2018 Feb 12;73(2):183–9. Available from:.
  94. Jin GY, Huang F, Kong JL. Sensitive determination of clomipramine at poly‐ABSA/Pt nano‐clusters modified glassy carbon electrode. Anal Lett. 2007 Dec 4;40(18):3392–404. Available from:.
  95. Ferancová A, Korgová E, Mikó R, Labuda J. Determination of tricyclic antidepressants using a carbon paste electrode modified with β-cyclodextrin. J Electroanal Chem. 2000 Sep;492(1):74–7. Available from:.
  96. Akhoundian M, Alizadeh T, Ganjali MR, Rafiei F. A new carbon paste electrode modified with MWCNTs and nano-structured molecularly imprinted polymer for ultratrace determination of trimipramine: The crucial effect of electrode components mixing on its performance. Biosens Bioelectron. 2018 Jul;111:27–33. Available from:.
  97. Kashi F, Ebrahimzadeh H, Nejabati F. Development and characterization of a non-enzymatic electrochemical biosensor for rapid determination of sorbent-based extracted trazodone and doxepin in complicated samples. Anal Chim Acta. 2024 Aug;1317:342902. Available from:.
  98. Lu H, Zhou W, Li Y, Yang M, Yang J, Hu C, et al. Machine-learning-optimized T3C2Tx/Bi2Se3 nanoflower-modified screen-printed electrodes for electrochemical detection of trace Pb2+ and Cd2+ in artificial sweat. Biosens Bioelectron. 2026 Apr;298:118389. Available from:.