, Volume 24, Issue 4, pp 1253–1263 | Cite as

Simultaneous electrochemical determination of isoniazid and ethambutol using poly-melamine/electrodeposited gold nanoparticles modified pre-anodized glassy carbon electrode

  • Zahra Sepehri
  • Hasan Bagheri
  • Elias Ranjbari
  • Mohaddeseh Amiri-Aref
  • Salimeh Amidi
  • Mohammad Reza Rouini
  • Yalda Hosseinzadeh Ardakani
Original Paper


For the first time, simultaneous voltammetric determination of two kinds of the first-line categorized anti-tuberculosis drugs including isoniazid (INZ) and ethambutol (EBL) was reported at a highly sensitive electrochemical sensor. The proposed sensor was successfully prepared based on an electroactive poly-melamine film and electrodeposited gold nanoparticles (PMel-Aunano)-modified pre-anodized glassy carbon electrode (GCE*). The morphological and electrochemical characteristics of the sensing surface (PMel-Aunano/GCE*) was well-characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The PMel-Aunano/GCE* exhibited strongly catalytic activity toward the oxidation of INZ (0.39 V potential shift) and EBL (0.29 V potential shift) in comparison with PMel/GCE* and bare GCE. Differential pulse voltammograms of INZ and EBL depicted the linear responses with their concentrations at the ranges of 0.3 to 170.0 μM and 0.5 to 150.0 μM, respectively. The detection limits for INZ and EBL were sequentially estimated as 0.08 and 0.21 μM. Furthermore, the developed electrochemical sensor was successfully implemented for the determination of INZ and EBL in real samples using standard addition method. This fabricated sensor showed to be promising for INZ and EBL detection with many desirable features including high-sensitivity, low detection limit, decrease in over-voltage, reproducible responses, and acceptable anti-interferences ability.


Electrocatalytic oxidation Simultaneous determination Poly-melamine Gold nanoparticles Isoniazid and ethambutol 



The authors gratefully acknowledge the support provided by the Researches Council of Zabol Medical Science University.


  1. 1.
    Thapliyal N, Karpoormath RV, Goyal RN (2015) Electroanalysis of antitubercular drugs in pharmaceutical dosage forms and biological fluids: a review. Anal Chim Acta 853:59–76CrossRefGoogle Scholar
  2. 2.
    Jindani A, Aber V, Edwards E, Mitchison D (1980) The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Revs Respir Dis 121(6):939–949Google Scholar
  3. 3.
    Belanger AE, Besra GS, Ford ME, Mikusová K, Belisle JT, Brennan PJ, Inamine JM (1996) The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc Natl Acad Sci 93(21):11919–11924CrossRefGoogle Scholar
  4. 4.
    Menzies D, Al Jahdali H, Al Otaibi B (2011) Recent developments in treatment of latent tuberculosis infection. Indian J Med Res 133(3):257Google Scholar
  5. 5.
    Caminero JA, Sotgiu G, Zumla A, Migliori GB (2010) Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis 10(9):621–629CrossRefGoogle Scholar
  6. 6.
    Balbão MS, Bertucci C, Bergamaschi MM, Queiroz RHC, Malfará WR, Dreossi SAC, de Paula ML, Queiroz MEC (2010) Rifampicin determination in plasma by stir bar-sorptive extraction and liquid chromatography. J Pharm Biomed Anal 51(5):1078–1083CrossRefGoogle Scholar
  7. 7.
    Espinosa-Mansilla A, Acedo-Valenzuela M, de la Pena AM, Cañada FC, López FS (2002) Determination of antitubercular drugs in urine and pharmaceuticals by LC using a gradient flow combined with programmed diode array photometric detection. Talanta 58(2):273–280CrossRefGoogle Scholar
  8. 8.
    Kenyon AS, Layloff T, Sherma J (2001) Rapid screening of tuberculosis pharmaceuticals by thin layer chromatography. J Liq Chromatogr Relat Technol 24(10):1479–1490CrossRefGoogle Scholar
  9. 9.
    Jiang Z, Wang H, Locke D (2002) Determination of ethambutol by ion-pair reversed phase liquid chromatography with UV detection. Anal Chim Acta 456(2):189–192CrossRefGoogle Scholar
  10. 10.
    Chenevier P, Massias L, Gueylard D, Farinotti R (1998) Determination of ethambutol in plasma by high-performance liquid chromatography after pre-column derivatization. J Chromatogr B 708(1):310–315CrossRefGoogle Scholar
  11. 11.
    Panchagnula R, Sood A, Sharda N, Kaur K, Kaul C (1999) Determination of rifampicin and its main metabolite in plasma and urine in presence of pyrazinamide and isoniazid by HPLC method. J Pharm Biomed Anal 18(6):1013–1020CrossRefGoogle Scholar
  12. 12.
    Conte JE, Lin E, Zhao Y, Zurlinden E (2002) A high-pressure liquid chromatographic-tandem mass spectrometric method for the determination of ethambutol in human plasma, bronchoalveolar lavage fluid, and alveolar cells. J Chromatogr Sci 40(2):113–118CrossRefGoogle Scholar
  13. 13.
    Fang P-F, Cai H-L, Zhu R-H, Tan Q-Y, Gao W, Xu P, Liu Y-P, Zhang W-Y, Chen Y-C, Zhang F (2010) Simultaneous determination of isoniazid, rifampicin, levofloxacin in mouse tissues and plasma by high performance liquid chromatography–tandem mass spectrometry. J Chromatogr B 878(24):2286–2291CrossRefGoogle Scholar
  14. 14.
    Breda M, Marrari P, Pianezzola E, Benedetti MS (1996) Determination of ethambutol in human plasma and urine by high-performance liquid chromatography with fluorescence detection. J Chromatogr A 729(1–2):301–307CrossRefGoogle Scholar
  15. 15.
    Bergamini MF, Santos DP, Zanoni MVB (2010) Determination of isoniazid in human urine using screen-printed carbon electrode modified with poly-L-histidine. Bioelectrochemistry 77(2):133–138CrossRefGoogle Scholar
  16. 16.
    Yang G, Wang C, Zhang R, Wang C, Qu Q, Hu X (2008) Poly (amidosulfonic acid) modified glassy carbon electrode for determination of isoniazid in pharmaceuticals. Bioelectrochemistry 73(1):37–42CrossRefGoogle Scholar
  17. 17.
    Rastogi PK, Ganesan V, Azad UP (2016) Electrochemical determination of nanomolar levels of isoniazid in pharmaceutical formulation using silver nanoparticles decorated copolymer. Electrochim Acta 188:818–824CrossRefGoogle Scholar
  18. 18.
    Absalan G, Akhond M, Soleimani M, Ershadifar H (2016) Efficient electrocatalytic oxidation and determination of isoniazid on carbon ionic liquid electrode modified with electrodeposited palladium nanoparticles. J Electroanal Chem 761:1–7CrossRefGoogle Scholar
  19. 19.
    Couto RA, Quinaz MB (2016) Development of a Nafion/MWCNT-SPCE-based portable sensor for the Voltammetric analysis of the anti-tuberculosis drug ethambutol. Sensors 16(7):1015–1027CrossRefGoogle Scholar
  20. 20.
    Lima A, Luz G, Batista N, Longo E, Cavalcante L, Santos R (2016) Determination of ethambutol in aqueous medium using an inexpensive gold microelectrode array as amperometric sensor. Electroanalysis 28(5):985–989CrossRefGoogle Scholar
  21. 21.
    Su Y-L, Cheng S-H (2015) Sensitive and selective determination of gallic acid in green tea samples based on an electrochemical platform of poly (melamine) film. Anal Chim Acta 901:41–50CrossRefGoogle Scholar
  22. 22.
    Cotchim S, Thavarungkul P, Kanatharana P, Limbut W (2015) A new strategy for 2,4,6-trinitrotoluene adsorption and electrochemical reduction on poly (melamine)/graphene oxide modified electrode. Electrochim Acta 184:102–110CrossRefGoogle Scholar
  23. 23.
    Amidi S, Hosseinzadeh Ardakani Y, Amiri-Aref M, Ranjbari E, Sepehri Z, Bagheri H (2017) Sensitive electrochemical determination of rifampicin using gold nanoparticles/poly-melamine nanocomposite. RSC Adv 7:40111–40118CrossRefGoogle Scholar
  24. 24.
    Afkhami A, Hashemi P, Bagheri H, Salimian J, Ahmadi A, Madrakian T (2017) Impedimetric immunosensor for the label-free and direct detection of botulinum neurotoxin serotype A using Au nanoparticles/graphene chitosan-composite. Biosens Bioelectron 93:124–131 754:118-124CrossRefGoogle Scholar
  25. 25.
    Li L, Liu E, Wang X, Chen J, Zhang X (2015) Simultaneous determination of naphthol isomers at poly (3-methylthiophene)-nano-Au modified electrode with the enhancement of surfactant. Mater Sci Eng C 53:36–42CrossRefGoogle Scholar
  26. 26.
    Tadayon F, Vahed S, Bagheri H (2016) Au-Pd/reduced graphene oxide composite as a new sensing layer for electrochemical determination of ascorbic acid, acetaminophen and tyrosine. Mater Sci Eng C 68:805–813CrossRefGoogle Scholar
  27. 27.
    Bagheri H, Talemi R, Afkhami A (2015) Gold nanoparticles deposited on fluorine-doped tin oxide surface as an effective platform for fabricating a highly sensitive and specific digoxin aptasensor. RSC Adv 5(72):58491–58498CrossRefGoogle Scholar
  28. 28.
    Koçak S, Aslışen B (2014) Hydrazine oxidation at gold nanoparticles and poly (bromocresol purple) carbon nanotube modified glassy carbon electrode. Sensors Actuators B Chem 196:610–618CrossRefGoogle Scholar
  29. 29.
    Wildgoose GG, Banks CE, Compton RG (2006) Metal nanoparticles and related materials supported on carbon nanotubes: methods and applications. Small 2(2):182–193CrossRefGoogle Scholar
  30. 30.
    Mohanty U (2011) Electrodeposition: a versatile and inexpensive tool for the synthesis of nanoparticles, nanorods, nanowires, and nanoclusters of metals. J Appl Electrochem 41(3):257–270CrossRefGoogle Scholar
  31. 31.
    Hezard T, Fajerwerg K, Evrard D, Collière V, Behra P, Gros P (2012) Gold nanoparticles electrodeposited on glassy carbon using cyclic voltammetry: application to Hg (II) trace analysis. J Electroanal Chem 664:46–52CrossRefGoogle Scholar
  32. 32.
    Li J, Lin X (2007) Electrocatalytic oxidation of hydrazine and hydroxylamine at gold nanoparticle-polypyrrole nanowire modified glassy carbon electrode. Sensors Actuators B Chem 126(2):527–535CrossRefGoogle Scholar
  33. 33.
    Li T, Xu J, Zhao L, Shen S, Yuan M, Liu W, Tu Q, Yu R, Wang J (2016) Au nanoparticles/poly (caffeic acid) composite modified glassy carbon electrode for voltammetric determination of acetaminophen. Talanta 159:356–364CrossRefGoogle Scholar
  34. 34.
    Baskar S, Liao C-W, Chang J-L, Zen J-M (2013) Electrochemical synthesis of electroactive poly (melamine) with mechanistic explanation and its applicability to functionalize carbon surface to prepare nanotube–nanoparticles hybrid. Electrochim Acta 88:1–5CrossRefGoogle Scholar
  35. 35.
    Saberi R-S, Shahrokhian S, Marrazza G (2013) Amplified electrochemical DNA sensor based on polyaniline film and gold nanoparticles. Electroanalysis 25:1373–1380CrossRefGoogle Scholar
  36. 36.
    Miao Z, Wang P, Zhong A, Yang M, Xu Q, Hao S, Hu X (2015) Development of a glucose biosensor based on electrodeposited gold nanoparticles-polyvinylpyrrolidone-polyaniline nanocomposites. J Electroanal Chem 756:153–160CrossRefGoogle Scholar
  37. 37.
    Finot M-O, Braybrook G-D, McDermott M-T (1999) Characterization of electrochemically deposited gold nanocrystals on glassy carbon electrodes. J Electroanal Chem 466:234–241CrossRefGoogle Scholar
  38. 38.
    Etesami M, Mohamed N (2011) Catalytic application of gold nanoparticles electrodeposited by fast scan cyclic voltammetry to glycerol electro-oxidation in alkaline electrolyte. Int J Electrochem Sci 6:4676–4689Google Scholar
  39. 39.
    Dai X, Nekrassova O, Hyde ME, Compton RG (2004) Anodic stripping voltammetry of arsenic (III) using gold nanoparticle-modified electrodes. Anal Chem 76(19):5924–5929CrossRefGoogle Scholar
  40. 40.
    El-Deab MS (2009) On the preferential crystallographic orientation of Au nanoparticles: effect of electrodeposition time. Electrochim Acta 54(14):3720–3725CrossRefGoogle Scholar
  41. 41.
    Shahrokhian S, Rastgar S (2012) Electrochemical deposition of gold nanoparticles on carbon nanotube coated glassy carbon electrode for the improved sensing of tinidazole. Electrochim Acta 78:422–429CrossRefGoogle Scholar
  42. 42.
    Bard AJ, Faulkner LR, Leddy J, Zoski CG (1980) Electrochemical methods: fundamentals and applications, vol 2. Wiley New York, New YorkGoogle Scholar
  43. 43.
    Bagheri H, Afkhami A, Khoshsafar H, Hajian A, Shahriyari AR (2017) Protein capped Cu nanoclusters-SWCNT nanocomposite as a novel candidate of high performance platform for organophosphates enzymeless biosensor. Biosens Bioelectron 89:829–836CrossRefGoogle Scholar
  44. 44.
    Fotouhi L, Nemati M, Heravi MM (2011) Electrochemistry and voltammetric determination of furazolidone with a multi-walled nanotube composite film-glassy carbon electrode. J Appl Electrochem 41(2):137–142CrossRefGoogle Scholar
  45. 45.
    Majidi MR, Jouyban A, Asadpour-Zeynali K (2006) Voltammetric behavior and determination of isoniazid in pharmaceuticals by using overoxidized polypyrrole glassy carbon modified electrode. J Electroanal Chem 589(1):32–37CrossRefGoogle Scholar
  46. 46.
    Devadas B, Cheemalapati S, Chen S-M, Ali MA, Al-Hemaid F-M (2015) Highly sensing graphene oxide/poly-arginine-modified electrode for the simultaneous electrochemical determination of buspirone, isoniazid and pyrazinamide drugs. Ionics 21(2):547–555CrossRefGoogle Scholar
  47. 47.
    Satyanarayana M, Reddy K-K, Gobi KV (2014) Multiwall carbon nanotube ensembled biopolymer electrode for selective determination of isoniazid in vitro. Anal Methods 6(11):3772–3778CrossRefGoogle Scholar
  48. 48.
    Shamsipur M, Fattahi N (2011) Extraction and determination of opium alkaloids in urine samples using dispersive liquid–liquid microextraction followed by high-performance liquid chromatography. J Chromatogr B 879:2978–2983CrossRefGoogle Scholar
  49. 49.
    Ranjbari E, Golbabanezhad-Azizi AA, Hadjmohammadi MR (2012) Preconcentration of trace amounts of methadone in human urine, plasma, saliva and sweat samples using dispersive liquid–liquid microextraction followed by high performance liquid chromatography. Talanta 94:116–122CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Zahra Sepehri
    • 1
  • Hasan Bagheri
    • 2
  • Elias Ranjbari
    • 3
  • Mohaddeseh Amiri-Aref
    • 3
  • Salimeh Amidi
    • 4
  • Mohammad Reza Rouini
    • 3
  • Yalda Hosseinzadeh Ardakani
    • 3
  1. 1.Department of Internal MedicineZabol University of Medical SciencesZabolIran
  2. 2.Chemical Injuries Research CenterBaqiyatallah University of Medical SciencesTehranIran
  3. 3.Biopharmaceutics and Pharmacokinetics Division, Department of Pharmaceutics, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  4. 4.Department of Medicinal Chemistry, School of PharmacyShahid Beheshti University of Medical SciencesTehranIran

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