Microchimica Acta

, 186:617 | Cite as

Modification of N,S co-doped graphene quantum dots with p-aminothiophenol-functionalized gold nanoparticles for molecular imprint-based voltammetric determination of the antiviral drug sofosbuvir

  • Ashraf M. Mahmoud
  • Mohamed M. El-WekilEmail author
  • Mater H. Mahnashi
  • Marwa F. B. Ali
  • Saad A. Alkahtani
Original Paper


A molecularly imprinted polymer (MIP) was developed for the electrochemical determination of the antiviral drug sofosbuvir (SOF). The MIP was obtained by polymerization of p-aminothiophenol (p-ATP) on N,S co-doped graphene quantum dots (N,S@GQDs) in the presence of gold nanoparticles to form gold-sulfur covalent network. The presence of quantum dots improves the electron transfer rate, enhances surface activity and amplifies the signal. The nanocomposites were characterized by FTIR, TEM, EDX, and SEM. The electrochemical performance of the electrode was investigated by differential pulse voltammetry and cyclic voltammetry. The sensor uses hexacyanoferrate as the redox probe and is best operated at a potential of around 0.36 V vs. Ag/AgCl. It has a linear response over the concentration range of 1–400 nM SOF, with a detection limit of 0.36 nM. Other features include high selectivity, good reproducibility and temporal stability. The sensor was applied to the determination of SOF in spiked human plasma.

Graphical abstract

Novel sofosbuvir imprinted p-ATP polymer was synthesized by the aid of gold nanoparticles on N,S co-doped graphene quantum dots as a good conductive support. The imprinted polymer was used for detection of sofosbuvir in real samples by using the ferri/ferrocyanide redox probe.


Electrochemical sensor Gold-sulfur covalent network Characterization techniques Selectivity Temporal stability Human plasma 



The authors thank the Deanship of Scientific Research, Najran University for funding the work; Project Code [NU/MID/16/032].

Compliance with ethical standards

The author(s) declare that they have no competing interest.

Ethical standards and informed consent

Collection of samples was from healthy volunteers at Assiut University Clinics. All experimental procedures and protocols were reviewed and approved by the ethics of Assiut University clinics, Assiut, Egypt. Informed consents were obtained from the human participants for this study.

Supplementary material

604_2019_3647_MOESM1_ESM.docx (690 kb)
ESM 1 (DOCX 690 KB)


  1. 1.
    Herbst DA, Reddy KR (2013) Sofosbuvir, a nucleotide polymerase inhibitor, for the treatment of chronic hepatitis C virus infection. Expert Opin Investig Drugs 22:527–536. CrossRefPubMedGoogle Scholar
  2. 2.
    Bhatia HK, Singh H, Grewal N, Natt NK (2014) Sofosbuvir: a novel treatment option for chronic hepatitis C infection. J Pharmacol Pharmacother 5:278–284. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    El-Wekil MM, Mahmoud AM, Marzouk AA, Alkahtani SA, Ali R (2018) A novel molecularly imprinted sensing platform based on MWCNTs/ AuNPs decorated 3D starfish like hollow nickel skeleton as a highly conductive nanocomposite for selective and ultrasensitive analysis of a novel pan-genotypic inhibitor velpatasvir in body fluids. J Mol Liq 271:105–111. CrossRefGoogle Scholar
  4. 4.
    Mansour FR (2018) A new innovative spectrophotometric method for the simultaneous determination of sofosbuvir and ledipasvir. Spectrochim Acta A Mol Biomol Spectrosc 188: 626-632. CrossRefGoogle Scholar
  5. 5.
    Salama FM, Attia KA, Abouserie AA, El-Olemy A, Abolmagd E (2017) Application of TLC densitometric method for simultaneous estimation of the newly co-formulated antiviral agents ledipasvir and sofosbuvir in their tablet dosage form. TACL 7:241–247. CrossRefGoogle Scholar
  6. 6.
    Abo-Zeid MN, El-Gizawy SM, Atia NN, El-Shaboury SR (2018) Efficient HPTLC-dual wavelength spectrodensitometric method for simultaneous determination of sofosbuvir and daclatasvir: biological and pharmaceutical analysis. J Pharm Biomed Anal 156:358–365. CrossRefPubMedGoogle Scholar
  7. 7.
    Zaman B, Siddique F, Hassan W (2016) RP-HPLC method for simultaneous determination of sofosbuvir and ledipasvir in tablet dosage form and its application to in vitro dissolution studies. Chromatographia 79:1605–1613. CrossRefGoogle Scholar
  8. 8.
    Vikas PM, Satyanarayana T, Kumar DV, Mounika E, Latha MS, Anusha R, Sathish Y (2016) Development and validation of new RP-HPLC method for the determination of sofosbuvir in pure form. World J Pharm Pharma Sci 5:775–781Google Scholar
  9. 9.
    Shi X, Zhu D, Lou J, Zhu B, Hu A, Gan D (2015) Evaluation of a rapid method for the simultaneous quantification of ribavirin, sofosbuvir and its metabolite in rat plasma by UPLC–MS/MS. J Chromatogr B 1002:353–357. CrossRefGoogle Scholar
  10. 10.
    Atta NF, Galal A, Ahmed YM (2018) Electrochemical method for the determination of three new anti-hepatitis C drugs: application in human blood serum. J Electrochem Soc 165:B442–B451. CrossRefGoogle Scholar
  11. 11.
    El-Wekil MM, Mahmoud AM, Alkahtani SS, Marzouk AA, Ali R (2018) A facile synthesis of 3D NiFe2O4 nanospheres anchored on a novel ionic liquid modified reduced graphene oxide for electrochemical sensing of ledipasvir: application to human pharmacokinetic study. Biosens Bioelectron 109:164–170. CrossRefPubMedGoogle Scholar
  12. 12.
    Wang Q, Ji J, Jiang D, Wang Y, Zhang Y, Sun Y (2014) An electrochemical sensor based on molecularly imprinted membranes on a p-ATP–AuNP modified electrode for the determination of acrylamide. Anal Methods 6:6452–6458CrossRefGoogle Scholar
  13. 13.
    Ansari S (2017) Combination of molecularly imprinted polymers and carbon nanomaterials as a versatile biosensing tool in sample analysis: recent applications and challenges. TrAC Trends Anal Chem 93:134–151CrossRefGoogle Scholar
  14. 14.
    Li H, Kang Z, Liu Y, Lee ST (2012) Carbon nanodots: synthesis, properties and applications. J Mater Chem 22:24230–24253. CrossRefGoogle Scholar
  15. 15.
    Baker SN, Baker GA (2010) Luminescent carbon nanodots: emergent nanolights. Angew Chem Int Ed 49:6726–6744. CrossRefGoogle Scholar
  16. 16.
    Liu JM, Lin LP, Wang XX, Lin SQ, Cai WL, Zhang LH, Zheng ZY (2012) Highly selective and sensitive detection of cu 2+ with lysine enhancing bovine serum albumin modified-carbon dots fluorescent probe. Analyst 137:2637–2642. CrossRefPubMedGoogle Scholar
  17. 17.
    Zhang R, Adsetts JR, Nie Y, Sun X, Ding Z (2018) Electrochemiluminescence of nitrogen- and sulfur-doped graphene quantum dots. Carbon 129:45–53. CrossRefGoogle Scholar
  18. 18.
    Liu JQ, Wulff G (2004) Molecularly imprinted polymers with strong carboxypeptidase like activity: combination of an amidinium function with a zinc-ion binding site in transition-state imprinted cavities. Angew Chem Int Ed 43:1287–1290. CrossRefGoogle Scholar
  19. 19.
    Li J, Rao X, Xiang F, Wei J, Yuan M, Liu Z (2018) A photoluminescence “switch-on” nanosensor composed of nitrogen and Sulphur co-doped carbon dots and gold nanoparticles for discriminative detection of glutathione. Analyst 143:2083–2089. CrossRefPubMedGoogle Scholar
  20. 20.
    Yola ML, Eren T, Atar N (2015) A sensitive molecular imprinted electrochemical sensor based on gold nanoparticles decorated graphene oxide: application to selective determination of tyrosine in milk. Sens Actuators B Chem 210:149–157. CrossRefGoogle Scholar
  21. 21.
    Yola ML, Atar N, Eren T (2014) Determination of amikacin in human plasma by molecular imprinted SPR nanosensor. Sens. Actuators B Chem. 198:70–76. CrossRefGoogle Scholar
  22. 22.
    Tonelli D, Ballarin B, Guadagnini L, Mignani A, Scavetta E (2011) A novel potentiometric sensor for l-ascorbic acid based on molecular imprinted polypyrrole. Electrochim Acta 56:7149–7154. CrossRefGoogle Scholar
  23. 23.
    Yang N, Wan Q, Yu J (2005) Adsorptive voltammetry of hg (II) ions at a glassy carbon electrode coated with electro-polymerized methyl-red film. Sens. Actuators B Chem. 110:246–251. CrossRefGoogle Scholar
  24. 24.
    Bruno JJB (2019) Molecularly imprinted polymers. Chem Rev 2019(119):94–119. CrossRefGoogle Scholar
  25. 25.
    Wang Y, Kim SH, Feng L (2015) Highly luminescent N, S- co-doped carbon dots and their direct use as mercury (II) sensor. Anal Chim Acta 890:134–142. CrossRefPubMedGoogle Scholar
  26. 26.
    Huang Q, Hu S, Zhang H, Chen J, He Y, Li F, Weng W, Ni J, Bao X, Lin Y (2013) Carbon dots and chitosan composite film based biosensor for the sensitive and selective determination of dopamine. Analyst 138:5417–5423. CrossRefPubMedGoogle Scholar
  27. 27.
    El-Wekil MM, Abdelhady KK, Abdel Salam RA, Hadad GM, Ali R (2019) Facile synthesis of novel nanocomposite prepared from spinel copper ferrite and reduced graphene oxide in the presence of anti-fouling agent diethyl ammonium acid sulphate for ultrasensitive detection of rosuvastatin in human plasma. Microchem J 147:1133–1140. CrossRefGoogle Scholar
  28. 28.
    Khashaba PY, Ali HRH, El-Wekil MM (2017) A new and cost effective approach for simultaneous voltammetric analysis of two related benzimidazole drugs and their determination in biological fluids. Electroanalysis 29:1643–1650CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, College of PharmacyNajran UniversityNajranSaudi Arabia
  2. 2.Department of Pharmaceutical Analytical Chemistry, Faculty of PharmacyAssiut UniversityAssiutEgypt
  3. 3.Department of Clinical Pharmacy, College of PharmacyNajran UniversityNajranSaudi Arabia

Personalised recommendations