, Volume 13, Issue 5, pp 1785–1793 | Cite as

Quantitative Detection of Thiopurines by Inter-particle Distance-Dependent Properties of Gold Nanoparticles

  • Shagun Kainth
  • Soumen BasuEmail author


As thiopurines are the source of chemotherapeutic drug which is helpful in treating acute lymphoblastic leukaemia, so the proper quantification of different purines is essential. As plasmonic nanoparticles (NPs) reported as colorimetric sensor due to their inter-particle variation in the presence of biomolecules. Here we have synthesised four different sizes (8–30 nm) gold nanoparticles (AuNPs) and chose as the analytical tool for the quantification of different purines. The characterisation of synthesised AuNPs was done by using FT-IR, TEM, DLS, EDS and UV-Vis spectroscopy. They showed remarkable stability for 10–15 days in the presence of long-range pH (3–12) and high concentration of the salt solution (100 μl, 0.1 M NaCl). Study of SPR variation was done for the quantification of purines. It has been seen that as the particle size, the concentration of purine and pH of the solution varies then SPR peak ~ 521 nm of AuNPs undergoes red shift and intensity of existing peak get reduced with time. The appearance of this new peak at ~ 700 nm justified the sensitivity of AuNPs towards purines. It was observed that the larger size AuNPs (30 nm) is more sensitive for detecting different purines at very low concentration (10−7 M for 6-thioguanine and 6-mercaptopurine).


Surface plasmon resonance Gold nanoparticles Aggregation Thiopurines Quantitative detection 


Funding Information

The authors are thankful to BRNS-DAE (Grant No: 34/14/63/2014) and SERB-DST (Grant No: SB/FT/CS-178/2013) for financial assistance. We are also thankful to DST-FIST, Sprint Testing solutions-Mumbai and Thapar University for providing instrumental facilities.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11468_2018_692_MOESM1_ESM.docx (115 kb)
ESM 1 (DOCX 115 kb)


  1. 1.
    Lennard L, Lilleyman JS, Van Loon J, Weinshilboum RM (1990) Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet 336(8709):225–229. CrossRefPubMedGoogle Scholar
  2. 2.
    Al-Ghobashy MA, Hassan SA, Abdelaziz DH, Elhosseiny NM, Sabry NA, Attia AS, el-Sayed MH (2016) Development and validation of LC-MS/MS assay for the simultaneous determination of methotrexate, 6-mercaptopurine and its active metabolite 6-thioguanine in plasma of children with acute lymphoblastic leukemia: correlation with genetic polymorphism. J Chromatogr B Anal Technol Biomed Life Sci 1038:88–94. CrossRefGoogle Scholar
  3. 3.
    Munshi P, Lubin M, Bertino J (2014) 6-thioguanine: a drug with unrealized potential for cancer therapy. Oncologist 19(7):760–765. CrossRefGoogle Scholar
  4. 4.
    Sean CS (2009) Martindale: the complete drug reference, 34th edn. Pharmaceutical Press, London, 884–886Google Scholar
  5. 5.
    Oancea I, Png CW, Das I, Lourie R, Winkler IG, Eri R, Subramaniam N, Jinnah HA, McWhinney BC, Levesque JP, McGuckin MA, Duley JA, Florin THJ (2013) A novel mouse model of veno-occlusive disease provides strategies to prevent thioguanine-induced hepatic toxicity. Gut 62(4):594–605. CrossRefPubMedGoogle Scholar
  6. 6.
    Tack GJ, Asseldonk DP, Wanrooij RLJ, Bodegraven AA, Mulder CJ (2012) Tioguanine in the treatment of refractory coeliac disease - a single centre experience. Aliment Pharmacol Ther 36(3):274–281. CrossRefPubMedGoogle Scholar
  7. 7.
    Fishman M, Mrozek-Orlowski M (1999) Cancer Chemotherapy Guidelines and Recommendations for Practice, 2nd edn. Oncology Nursing Press Inc, Pittsburgh PA, pp 25Google Scholar
  8. 8.
    Madueño R, Pineda T, Sevilla JM, Blázquez M (2004) An electrochemical study of 6-thioguanine monolayers on a mercury electrode in acid and neutral solutions. J Electroanal Chem 565(2):301–310. CrossRefGoogle Scholar
  9. 9.
    Rowland K, Lennard L, Lilleyman JS (1998) High-performance liquid chromatographic assay of methylthioguanine nucleotide. J Chromatogr B Biomed Sci Appl 705(1):29–37. CrossRefPubMedGoogle Scholar
  10. 10.
    Mawatari H, Kato Y, Nishimura SI et al (1998) Reversed-phase high-performance liquid chromatographic assay method for quantitating 6-mercaptopurine and its methylated and non-methylated metabolites in a single sample. J Chromatogr B Biomed Appl 716(1-2):392–396. CrossRefGoogle Scholar
  11. 11.
    Keuzenkamp-Jansen CW, De Abreu RA, Bökkerink JPM, Trijbels JMF (1995) Determination of extracellular and intracellular thiopurines and methylthiopurines by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 672(1):53–61. CrossRefGoogle Scholar
  12. 12.
    Lennard L, Singleton HJ (1992) High-performance liquid chromatographic assay of the methyl and nucleotide metabolites of 6-mercaptopurine: quantitation of red blood cell 6-thioguanine nucleotide, 6-thioinosinic acid and 6-methylmercaptopurine metabolites in a single sample. J Chromatogr B Biomed Sci Appl 583(1):83–90. CrossRefGoogle Scholar
  13. 13.
    Lennard L (1987) Assay of 6-thioinosinic acid and 6-thioguanine nucleotides, active metabolites of 6_mercaptopurine, in human red blood cells. J Chromatogr Biomed Appl Elsevier Sci Publ BV 423:169–178. CrossRefGoogle Scholar
  14. 14.
    Lennard L (1985) Assay of 6-mercaptopurine in human plasma. J Chromatogr B Biomed Sci Appl 345:441–446. CrossRefGoogle Scholar
  15. 15.
    Lavi LE, Holcenberg JS (1985) A rapid and sensitive high-performance liquid chromatographic assay for 6-mercaptopurine metabolites in red blood cells. Anal Biochem 144(2):514–521. CrossRefPubMedGoogle Scholar
  16. 16.
    Basu S, Ghosh SK, Kundu S, Panigrahi S, Praharaj S, Pande S, Jana S, Pal T (2007) Biomolecule induced nanoparticle aggregation: effect of particle size on interparticle coupling. J Colloid Interface Sci 313(2):724–734. CrossRefPubMedGoogle Scholar
  17. 17.
    Zhong Z, Patskovskyy S, Bouvrette P, Luong JHT, Gedanken A (2004) The surface chemistry of Au colloids and their interactions with functional amino acids. J Phys Chem B 108(13):4046–4052. CrossRefGoogle Scholar
  18. 18.
    Lubomirsky I, Wang TY, Gartsman K et al (2000) Biologically programmed nanoparticle assembly. Adv Mater 12(2):147–150.<147::AID-ADMA147>3.0.CO;2-U CrossRefGoogle Scholar
  19. 19.
    Mrksich M (2000) A surface chemistry approach to studying cell adhesion. Chem Soc Rev 29(4):267–273. CrossRefGoogle Scholar
  20. 20.
    Bright RM, Walter DG, Musick MD, Jackson MA, Allison KJ, Natan MJ (1996) Chemical and electrochemical Ag deposition onto preformed Au colloid monolayers: approaches to uniformly-sized surface features with Ag-like optical properties. Langmuir 12(3):810–817. CrossRefGoogle Scholar
  21. 21.
    Alvarez MM, Khoury JT, Schaaff TG, Shafigullin MN, Vezmar I, Whetten RL (1997) Optical absorption spectra of nanocrystal gold molecules. J Phys Chem B 101(19):3706–3712. CrossRefGoogle Scholar
  22. 22.
    Takeuchi Y, Ida T, Kimura K (1996) Temperature effect on gold nanodispersion in organic liquids. Surf Rev Lett 3(01):1205–1208. CrossRefGoogle Scholar
  23. 23.
    Kreibig U, Genzel L (1985) Optical absorption of small metallic particles. Surf Sci 156:678–700. CrossRefGoogle Scholar
  24. 24.
    Thanh NTK, Rosenzweig Z (2002) Development of an aggregation-based immunoassay for anti-protein A using gold nanoparticles. Abstr Pap Am Chem Soc 223:U74–U74Google Scholar
  25. 25.
    Andrew Lyon L, Musick MD, Natan MJ (1998) Colloidal Au-enhanced surface plasmon resonance immunosensing. Anal Chem 70(24):5177–5183. CrossRefGoogle Scholar
  26. 26.
    Musick MD, Keating CD, Lyon LA, Botsko SL, Peña DJ, Holliway WD, McEvoy TM, Richardson JN, Natan MJ (2000) Metal films prepared by stepwise assembly. 2. Construction and characterization of colloidal Au and Ag multilayers. Chem Mater 12(10):2869–2881. CrossRefGoogle Scholar
  27. 27.
    Storhoff JJ, Mucic RC, Mirkin CA (1997) Strategies for Organizing Nanoparticles into Aggregate Structures and Functional Materials. J Clust Sci 8:179–216. CrossRefGoogle Scholar
  28. 28.
    Freeman RG, Grabar KC, Allison KJ et al (1995) Self-assembled metal colloid monolayers: an approach to SERS substrates. Science 267(80):1629–1632. CrossRefPubMedGoogle Scholar
  29. 29.
    Taton T, Mirkin C, Letsinger R (2000) Scanometric DNA array detection with nanoparticle probes. Science 289(5485):1757–1760. CrossRefPubMedGoogle Scholar
  30. 30.
    Storhoff JJ, Elghanian R, Mucic RC, Mirkin CA, Letsinger RL (1998) One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes. J Am Chem Soc 7863(9):1959–1964. CrossRefGoogle Scholar
  31. 31.
    Elghanian R, Storhoff JJ, Mucic RC et al (2010) Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science 1078(80):1078–1081. CrossRefGoogle Scholar
  32. 32.
    Templeton AC, Chen S, Gross SM, Murray RW (1999) Water-soluble, isolable gold clusters protected by tiopronin and coenzyme A monolayers. Langmuir 15(1):66–76. CrossRefGoogle Scholar
  33. 33.
    Physik ADER, Vol N (1908) Beiträge zur Optik trüber Medien, speziell kolloidaller Metallösungen; von Gustav Mie. Ann Phys 25:1–52Google Scholar
  34. 34.
    Basu S, Pande S, Jana S, et al (2008) Controlled Interparticle Spacing for Surface-Modified Gold Nanoparticle Aggregates Controlled Interparticle Spacing for Surface-Modified Gold Nanoparticle Aggregates. Langmuir 8276–8282. CrossRefGoogle Scholar
  35. 35.
    Park J, Shumaker-parry JS (2005) Structural study of citrate layers on gold nanoparticles: role of intermolecular interactions in stabilizing nanoparticles. Langmuir 21(21):1–33. CrossRefGoogle Scholar
  36. 36.
    Park JW, Shumaker-Parry JS (2014) Structural study of citrate layers on gold nanoparticles: role of intermolecular interactions in stabilizing nanoparticles. J Am Chem Soc 136(5):1907–1921. CrossRefPubMedGoogle Scholar
  37. 37.
    Olesen KM, Hansen SH, Sidenius U, Schmiegelow K (2008) Determination of leukocyte DNA 6-thioguanine nucleotide levels by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Anal Technol Biomed Life Sci 864(1-2):149–155. CrossRefGoogle Scholar
  38. 38.
    Warren DJ, Slørdal L (1993) A high-performance liquid chromatographic method for the determination of 6-thioguanine residues in DNA using precolumn derivatization and fluorescence detection. Anal Biochem 215(2):278–283. CrossRefPubMedGoogle Scholar
  39. 39.
    Thomas A (1976) Spectrofluorometric determination of thiopurines—I: 6-Thioguanine. Talanta 23(5):383–386. CrossRefPubMedGoogle Scholar
  40. 40.
    Wang W, Wang SF, Xie F (2006) An electrochemical sensor of non-electroactive drug 6-thioguanine based on the dsDNA/AET/Au. Sensors Actuators B Chem 120(1):238–244. CrossRefGoogle Scholar
  41. 41.
    Mirmomtaz E, Ensafi AA, Karimi-Maleh H (2008) Electrocatalytic determination of 6-tioguanine at a p-aminophenol modified carbon paste electrode. Electroanalysis 20(18):1973–1979. CrossRefGoogle Scholar
  42. 42.
    Ensafi AA, Karimi-Maleh H (2010) Modified multiwall carbon nanotubes paste electrode as a sensor for simultaneous determination of 6-thioguanine and folic acid using ferrocenedicarboxylic acid as a mediator. J Electroanal Chem 640(1-2):75–83. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Chemistry and BiochemistryThapar Institute of Engineering and Technology (Deemed University)PatialaIndia

Personalised recommendations