Determination of norepinephrine using a glassy carbon electrode modified with graphene quantum dots and gold nanoparticles by square wave stripping voltammetry

  • A. Fajardo
  • D. Tapia
  • J. PizarroEmail author
  • R. SeguraEmail author
  • P. Jara
Research Article
Part of the following topical collections:
  1. Sensors
  2. Sensors


In this work, a glassy carbon electrode modified with graphene quantum dots and gold nanoparticles (GCE/GQDs/AuNPs) was developed for norepinephrine (NE) determination using squarewave stripping voltammetry. GQDs were synthesized by citric acid pyrolysis and characterized by UV–Vis and fluorescence spectroscopy. The chemically synthesized AuNPs were characterized by transmission electron microscopy and UV–Vis spectroscopy (Plasmon Band). GCE/GQDs surface was characterized by Raman spectroscopy and scanning electron microscopy. The conditions for the determination of NE with GCE/GQDs/AuNPs were optimized. The linear range was observed between 0.5 and 7.5 µmol L−1, with a detection limit (LOD) of 0.15 µmol L−1. The proposed methodology was validated with spiked samples for good precision and accuracy. GCE/GQDs/AuNPs were used in pharmaceutical preparations (NE ampoules) and in rat brain tissue with satisfactory results.

Graphical abstract


Graphene quantum dots Gold nanoparticles Electrochemical sensor Squarewave stripping voltammetry Norepinephrine 



The authors thank to FONDECYT Chile, for financial support under project No. 1180804, “Comisión Nacional de Investigación Científica y Tecnológica” (CONICYT) for doctoral fellowship 21150242, Dirección de Investigación Científica y Tecnológica (DICYT).


  1. 1.
    Baum B (1987) Neurotransmitter control of secretion. J Dent Res 66:628–632CrossRefGoogle Scholar
  2. 2.
    GLOWINSKI J, BALDESSARINI RJ (1966) Metabolism of norepinephrine in the central nervous system. Pharmacol Rev 18:1201–1238Google Scholar
  3. 3.
    Bard P (1929) The central representation of the sympathetic system: as indicated by certain physiologic observations. Arch Neurol Psychiatry 22:230–246CrossRefGoogle Scholar
  4. 4.
    Sofuoglu M, Sewell RA (2009) Review: norepinephrine and stimulant addiction. Addict Biol 14:119–129CrossRefGoogle Scholar
  5. 5.
    Liu A-L, Zhang S-B, Chen W, Lin X-H, Xia X-H (2008) Simultaneous voltammetric determination of norepinephrine, ascorbic acid and uric acid on polycalconcarboxylic acid modified glassy carbon electrode. Biosens Bioelectron 23:1488–1495CrossRefGoogle Scholar
  6. 6.
    De Benedetto GE, Fico D, Pennetta A, Malitesta C, Nicolardi G, Lofrumento DD, De Nuccio F, La Pesa V (2014) A rapid and simple method for the determination of 3, 4-dihydroxyphenylacetic acid, norepinephrine, dopamine, and serotonin in mouse brain homogenate by HPLC with fluorimetric detection. J Pharm Biomed Anal 98:266–270CrossRefGoogle Scholar
  7. 7.
    Wei S, Song G, Lin J-M (2005) Separation and determination of norepinephrine, epinephrine and isoprinaline enantiomers by capillary electrophoresis in pharmaceutical formulation and human serum. J Chromatogr A 1098:166–171CrossRefGoogle Scholar
  8. 8.
    Sorouraddin M, Manzoori J, Kargarzadeh E, Shabani AH (1998) Spectrophotometric determination of some catecholamine drugs using sodium bismuthate. J Pharm Biomed Anal 18:877–881CrossRefGoogle Scholar
  9. 9.
    Haque A-MJ, Park H, Sung D, Jon S, Choi S-Y, Kim K (2012) An electrochemically reduced graphene oxide-based electrochemical immunosensing platform for ultrasensitive antigen detection. Anal Chem 84:1871–1878CrossRefGoogle Scholar
  10. 10.
    Sajid M, Nazal MK, Mansha M, Alsharaa A, Jillani SMS, Basheer C (2016) Chemically modified electrodes for electrochemical detection of dopamine in the presence of uric acid and ascorbic acid: a review. TrAC Trends Anal Chem 76:15–29CrossRefGoogle Scholar
  11. 11.
    Sanghavi BJ, Wolfbeis OS, Hirsch T, Swami NS (2015) Nanomaterial-based electrochemical sensing of neurological drugs and neurotransmitters. Microchim Acta 182:1–41CrossRefGoogle Scholar
  12. 12.
    Wang J (2005) Nanomaterial-based electrochemical biosensors. Analyst 130:421–426CrossRefGoogle Scholar
  13. 13.
    Zhao Q, Gan Z, Zhuang Q (2002) Electrochemical sensors based on carbon nanotubes. Electroanalysis 14:1609–1613CrossRefGoogle Scholar
  14. 14.
    Yang W, Ratinac KR, Ringer SP, Thordarson P, Gooding JJ, Braet F (2010) Carbon nanomaterials in biosensors: should you use nanotubes or graphene? Angew Chem Int Ed 49:2114–2138CrossRefGoogle Scholar
  15. 15.
    Elyasi M, Khalilzadeh MA, Karimi-Maleh H (2013) High sensitive voltammetric sensor based on Pt/CNTs nanocomposite modified ionic liquid carbon paste electrode for determination of Sudan I in food samples. Food Chem 141:4311–4317CrossRefGoogle Scholar
  16. 16.
    Keyvanfard M, Shakeri R, Karimi-Maleh H, Alizad K (2013) Highly selective and sensitive voltammetric sensor based on modified multiwall carbon nanotube paste electrode for simultaneous determination of ascorbic acid, acetaminophen and tryptophan. Mater Sci Eng: C 33:811–816CrossRefGoogle Scholar
  17. 17.
    Dogan-Topal B, Bozal-Palabıyık B, Uslu B, Ozkan SA (2013) Multi-walled carbon nanotube modified glassy carbon electrode as a voltammetric nanosensor for the sensitive determination of anti-viral drug valganciclovir in pharmaceuticals. Sens Actuators B 177:841–847CrossRefGoogle Scholar
  18. 18.
    Gupta VK, Jain AK, Shoora SK (2013) Multiwall carbon nanotube modified glassy carbon electrode as voltammetric sensor for the simultaneous determination of ascorbic acid and caffeine. Electrochim Acta 93:248–253CrossRefGoogle Scholar
  19. 19.
    Ensafi AA, Izadi M, Karimi-Maleh H (2013) Sensitive voltammetric determination of diclofenac using room-temperature ionic liquid-modified carbon nanotubes paste electrode. Ionics 19:137–144CrossRefGoogle Scholar
  20. 20.
    Kerman K, Saito M, Tamiya E, Yamamura S, Takamura Y (2008) Nanomaterial-based electrochemical biosensors for medical applications. TrAC Trends Anal Chem 27:585–592CrossRefGoogle Scholar
  21. 21.
    Li Y, Jiang Y, Mo T, Zhou H, Li Y, Li S (2016) Highly selective dopamine sensor based on graphene quantum dots self-assembled monolayers modified electrode. J Electroanal Chem 767:84–90CrossRefGoogle Scholar
  22. 22.
    Jian X, Liu X, Yang H-M, Guo M-M, Song X-L, Dai H-Y, Liang Z-H (2016) Graphene quantum dots modified glassy carbon electrode via electrostatic self-assembly strategy and its application. Electrochim Acta 190:455–462CrossRefGoogle Scholar
  23. 23.
    Bacon M, Bradley SJ, Nann T (2014) Graphene quantum dots. Part Part Syst Charact 31:415–428CrossRefGoogle Scholar
  24. 24.
    Jin SH, Kim DH, Jun GH, Hong SH, Jeon S (2013) Tuning the photoluminescence of graphene quantum dots through the charge transfer effect of functional groups. ACS Nano 7:1239–1245CrossRefGoogle Scholar
  25. 25.
    Zhang S, Wang N, Yu H, Niu Y, Sun C (2005) Covalent attachment of glucose oxidase to an Au electrode modified with gold nanoparticles for use as glucose biosensor. Bioelectrochemistry 67:15–22CrossRefGoogle Scholar
  26. 26.
    Daniel M-C, Astruc D (2004) Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 104:293–346CrossRefGoogle Scholar
  27. 27.
    Khater M, de la Escosura-Muñiz A, Quesada-González D, Merkoçi A (2019) Electrochemical detection of plant virus using gold nanoparticle-modified electrodes, 1046:123–131Google Scholar
  28. 28.
    Yola ML, Atar N (2014) A novel voltammetric sensor based on gold nanoparticles involved in p-aminothiophenol functionalized multi-walled carbon nanotubes: application to the simultaneous determination of quercetin and rutin. Electrochim Acta 119:24–31CrossRefGoogle Scholar
  29. 29.
    Sanghavi BJ, Kalambate PK, Karna SP, Srivastava AK (2014) Voltammetric determination of sumatriptan based on a graphene/gold nanoparticles/nafion composite modified glassy carbon electrode. Talanta 120:1–9CrossRefGoogle Scholar
  30. 30.
    Mirmoghtadaie L, Ensafi AA, Kadivar M, Shahedi M, Ganjali MR (2013) Highly selective, sensitive and fast determination of folic acid in food samples using new electrodeposited gold nanoparticles by differential pulse voltammetry. Int J Electrochem Sci 8:3755–3767Google Scholar
  31. 31.
    Zhu L, Xu L, Huang B, Jia N, Tan L, Yao S (2014) Simultaneous determination of Cd (II) and Pb (II) using square wave anodic stripping voltammetry at a gold nanoparticle-graphene-cysteine composite modified bismuth film electrode. Electrochim Acta 115:471–477CrossRefGoogle Scholar
  32. 32.
    Han H, Pan D, Liu D, Hu X, Lin M, Li F (2015) Cathodic stripping voltammetric determination of chromium in coastal waters on cubic nano-titanium carbide loaded gold nanoparticles modified electrode. Front Mar Sci 2:75CrossRefGoogle Scholar
  33. 33.
    Wong A, Razzino CA, Silva TA, Fatibello-Filho O (2016) Square-wave voltammetric determination of clindamycin using a glassy carbon electrode modified with graphene oxide and gold nanoparticles within a crosslinked chitosan film. Sens Actuators B 231:183–193CrossRefGoogle Scholar
  34. 34.
    da Silva W, Ghica ME, Ajayi RF, Iwuoha EI, Brett CMJFC (2019) Tyrosinase based amperometric biosensor for determination of tyramine in fermented food and beverages with gold nanoparticle doped poly (8-anilino-1-naphthalene sulphonic acid) modified electrode. Food Chem 282:18–26CrossRefGoogle Scholar
  35. 35.
    Beitollahi H, Safaei M, Tajik SJA, Research BC (2019) Different electrochemical sensors for determination of dopamine as neurotransmitter in mixed and clinical samples. Review 6:81–96Google Scholar
  36. 36.
    Dong Y, Shao J, Chen C, Li H, Wang R, Chi Y, Lin X, Chen G (2012) Blue luminescent graphene quantum dots and graphene oxide prepared by tuning the carbonization degree of citric acid. Carbon 50:4738–4743CrossRefGoogle Scholar
  37. 37.
    Pande S, Ghosh SK, Praharaj S, Panigrahi S, Basu S, Jana S, Pal A, Tsukuda T, Pal T (2007) Synthesis of normal and inverted gold-silver core-shell architectures in β-cyclodextrin and their applications in SERS. J Phys Chem C 111:10806–10813CrossRefGoogle Scholar
  38. 38.
    Chi J, Odontiadis J, Franklin M (1999) Simultaneous determination of catecholamines in rat brain tissue by high-performance liquid chromatography. J Chromatogr B 731:361–367CrossRefGoogle Scholar
  39. 39.
    Cruz G (2014) Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat. Horm Metab Res 46:322–327Google Scholar
  40. 40.
    Tang L, Ji R, Cao X, Lin J, Jiang H, Li X, Teng KS, Luk CM, Zeng S, Hao J (2012) Deep ultraviolet photoluminescence of water-soluble self-passivated graphene quantum dots. ACS Nano 6:5102–5110CrossRefGoogle Scholar
  41. 41.
    Luo Z, Lu Y, Somers LA, Johnson AC (2009) High yield preparation of macroscopic graphene oxide membranes. J Am Chem Soc 131:898–899CrossRefGoogle Scholar
  42. 42.
    Peng J, Gao W, Gupta BK, Liu Z, Romero-Aburto R, Ge L, Song L, Alemany LB, Zhan X, Gao G (2012) Graphene quantum dots derived from carbon fibers. Nano Lett 12:844–849CrossRefGoogle Scholar
  43. 43.
    Li LL, Ji J, Fei R, Wang CZ, Lu Q, Zhang JR, Jiang LP, Zhu JJ (2012) A facile microwave avenue to electrochemiluminescent two-color graphene quantum dots. Adv Func Mater 22:2971–2979CrossRefGoogle Scholar
  44. 44.
    Ting SL, Ee SJ, Ananthanarayanan A, Leong KC, Chen P (2015) Graphene quantum dots functionalized gold nanoparticles for sensitive electrochemical detection of heavy metal ions. Electrochim Acta 172:7–11CrossRefGoogle Scholar
  45. 45.
    Guo CX, Yang HB, Sheng ZM, Lu ZS, Song QL, Li CM (2010) Layered graphene/quantum dots for photovoltaic devices. Angew Chem Int Ed 49:3014–3017CrossRefGoogle Scholar
  46. 46.
    Link S, El-Sayed MA (1999) Size and temperature dependence of the plasmon absorption of colloidal gold nanoparticles. J Phys Chem B 103:4212–4217CrossRefGoogle Scholar
  47. 47.
    Eustis S, El-Sayed MA (2006) Why gold nanoparticles are more precious than pretty gold: Noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. Chem Soc Rev 35:209–217CrossRefGoogle Scholar
  48. 48.
    Chen H, Wang Y, Wang Y, Dong S, Wang E (2006) One-step preparation and characterization of PDDA-protected gold nanoparticles. Polymer 47:763–766CrossRefGoogle Scholar
  49. 49.
    Tuinstra F, Koenig JL (1970) Raman spectrum of graphite. J Chem Phys 53:1126–1130CrossRefGoogle Scholar
  50. 50.
    Tetsuka H, Asahi R, Nagoya A, Okamoto K, Tajima I, Ohta R, Okamoto A (2012) Optically tunable amino-functionalized graphene quantum dots. Adv Mater 24:5333–5338CrossRefGoogle Scholar
  51. 51.
    Li Y, Zhao Y, Cheng H, Hu Y, Shi G, Dai L, Qu L (2011) Nitrogen-doped graphene quantum dots with oxygen-rich functional groups. J Am Chem Soc 134:15–18CrossRefGoogle Scholar
  52. 52.
    Tang J, Huang R, Zheng S, Jiang S, Yu H, Li Z, Wang JJMJ (2019) A sensitive and selective electrochemical sensor based on graphene quantum dots/gold nanoparticles nanocomposite modified electrode for the determination of luteolin in peanut hulls. Microchem J 145:899–907CrossRefGoogle Scholar
  53. 53.
    Jie G, Zhou Q, Jie GJT (2019) Graphene quantum dots-based electrochemiluminescence detection of DNA using multiple cycling amplification strategy. Talenta 194:658–663CrossRefGoogle Scholar
  54. 54.
    Shetti NP, Nayak DS, Malode SJ, Kulkarni RM (2017) An electrochemical sensor for clozapine at ruthenium doped TiO2 nanoparticles modified electrode. Sens Actuators B 247:858–867CrossRefGoogle Scholar
  55. 55.
    Bagheri H, Afkhami A, Hashemi P, Ghanei M (2015) Simultaneous and sensitive determination of melatonin and dopamine with Fe3O4 nanoparticle-decorated reduced graphene oxide modified electrode. RSC Adv 5:21659–21669CrossRefGoogle Scholar
  56. 56.
    Niu X, Yang W, Guo H, Ren J, Gao J (2013) Highly sensitive and selective dopamine biosensor based on 3, 4, 9, 10-perylene tetracarboxylic acid functionalized graphene sheets/multi-wall carbon nanotubes/ionic liquid composite film modified electrode. Biosens Bioelectron 41:225–231CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Departamento de Química de los Materiales, Facultad de Química y BiologíaUniversidad de Santiago de Chile (USACH)SantiagoChile
  2. 2.Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Personalised recommendations