Analytical and Bioanalytical Chemistry

, Volume 398, Issue 1, pp 77–92 | Cite as

Counterfeit drugs: analytical techniques for their identification

  • R. Martino
  • M. Malet-Martino
  • V. Gilard
  • S. Balayssac


In recent years, the number of counterfeit drugs has increased dramatically, including not only “lifestyle” products but also vital medicines. Besides the threat to public health, the financial and reputational damage to pharmaceutical companies is substantial. The lack of robust information on the prevalence of fake drugs is an obstacle in the fight against drug counterfeiting. It is generally accepted that approximately 10% of drugs worldwide could be counterfeit, but it is also well known that this number covers very different situations depending on the country, the places where the drugs are purchased, and the definition of what constitutes a counterfeit drug. The chemical analysis of drugs suspected to be fake is a crucial step as counterfeiters are becoming increasingly sophisticated, rendering visual inspection insufficient to distinguish the genuine products from the counterfeit ones. This article critically reviews the recent analytical methods employed to control the quality of drug formulations, using as an example artemisinin derivatives, medicines particularly targeted by counterfeiters. Indeed, a broad panel of techniques have been reported for their analysis, ranging from simple and cheap in-field ones (colorimetry and thin-layer chromatography) to more advanced laboratory methods (mass spectrometry, nuclear magnetic resonance, and vibrational spectroscopies) through chromatographic methods, which remain the most widely used. The conclusion section of the article highlights the questions to be posed before selecting the most appropriate analytical approach.


DOSY spectrum of a counterfeit artesunate tablet containing paracetamol instead of artesunate


Counterfeit drugs Colorimetry Chromatography Mass spectrometry Diffusion-ordered 1H NMR spectroscopy Vibrational spectroscopies 


  1. 1.
    Europharm Forum (2009) Framework for a guide on counterfeit medicines for pharmacists. Accessed 6 Feb 2010
  2. 2.
    World Health Organization (1999) WHO counterfeit drugs. Guidelines for the development of measures to combat counterfeit drugs, vol 99.1. World Health Organization, Geneva. Accessed 6 Feb 2010
  3. 3.
    Newton PN, Lee SJ, Goodman C, Fernandez FM, Yeung S, Phanouvong S, Kaur H, Amin AA, Whitty CJM, Kokwaro GO, Lindegardh N, Lukulay P, White LJ, Day NPJ, Green MD, White NJ (2009) PLoS Med 6:e1000052CrossRefGoogle Scholar
  4. 4.
    World Health Organization (2008) WHO world malaria report-2008. Accessed 6 Feb 2010
  5. 5.
    Newton PN, Green MD, Fernandez FM, Day NPJ, White NJ (2006) Lancet Infect Dis 6:602–613CrossRefGoogle Scholar
  6. 6.
    World Health Organization (2006) Guidelines for the treatment of malaria. Accessed 6 Feb 2010
  7. 7.
    Thomas CG, Ward SA, Edwards G (1992) J Chromatogr 583:131–136CrossRefGoogle Scholar
  8. 8.
    Green MD, Mount DL, Wirtz RA, White NJ (2000) J Pharm Biomed Anal 24:65–70CrossRefGoogle Scholar
  9. 9.
    Green MD, Mount DL, Wirtz RA (2001) Trop Med Int Health 6:980–982CrossRefGoogle Scholar
  10. 10.
    Ioset JR, Kaur H (2009) PLoS One 4:e7270CrossRefGoogle Scholar
  11. 11.
    Green MD, Nettey H, Rojas OV, Pamanivong C, Khounsaknalath L, Ortiz MG, Newton PN, Fernandez FM, Vongsack L, Manolin O (2007) J Pharm Biomed Anal 43:105–110CrossRefGoogle Scholar
  12. 12.
    Atemnkeng MA, De Cock K, Plaizier-Vercammen J (2007) Trop Med Int Health 12:68–74Google Scholar
  13. 13.
    Atemnkeng MA, Marchand E, Plaizier-Vercammen J (2007) J Pharm Biomed Anal 43:727–732CrossRefGoogle Scholar
  14. 14.
    Cesar IDC, Nogueira FHA, Pianetti GA (2008) J Pharm Biomed Anal 48:951–954CrossRefGoogle Scholar
  15. 15.
    Gaudin K, Kauss T, Lagueny AM, Millet P, Fawaz F, Dubost JP (2009) J Sep Sci 32:231–237CrossRefGoogle Scholar
  16. 16.
    Hall KA, Newton PN, Green MD, de Veij M, Vandenabeele P, Pizzanelli D, Mayxay M, Dondorp A, Fernandez FM (2006) Am J Trop Med Hyg 75:804–811Google Scholar
  17. 17.
    Lindegardh N, Dondorp AM, Singhasivanon P, White NJ, Day NPJ (2007) J Pharm Biomed Anal 45:149–153CrossRefGoogle Scholar
  18. 18.
    Fernandez FM, Cody RB, Green MD, Hampton CY, McGready R, Sengaloundeth S, White NJ, Newton PN (2006) Chemmedchem 1:702–705CrossRefGoogle Scholar
  19. 19.
    Nyadong L, Green MD, De Jesus VR, Newton PN, Fernandez FM (2007) Anal Chem 79:2150–2157CrossRefGoogle Scholar
  20. 20.
    Nyadong L, Harris GA, Balayssac S, Galhena AS, Malet-Martino M, Martino R, Parry RM, Wang MD, Fernandez FM, Gilard V (2009) Anal Chem 81:4803–4812CrossRefGoogle Scholar
  21. 21.
    Nyadong L, Late S, Green MD, Banga A, Fernandez FM (2008) J Am Soc Mass Spectrom 19:380–388CrossRefGoogle Scholar
  22. 22.
    Ricci C, Nyadong L, Fernandez FM, Newton PN, Kazarian SG (2007) Anal Bioanal Chem 387:551–559CrossRefGoogle Scholar
  23. 23.
    Ricci C, Nyadong L, Yang F, Fernandez FM, Brown CD, Newton PN, Kazarian SG (2008) Anal Chim Acta 623:178–186CrossRefGoogle Scholar
  24. 24.
    Newton PN, Fernandez FM, Plançon A, Mildenhall DC, Green MD, Ziyong L, Christophel EM, Phanouvong S, Howells S, McIntosh E, Laurin P, Blum N, Hampton CY, Faure K, Nyadong L, Soong CWR, Santoso B, Zhiguang W, Newton J, Palmer K (2008) PLoS Med 5:e32CrossRefGoogle Scholar
  25. 25.
    Ricci C, Eliasson C, Macleod NA, Newton PN, Matousek P, Kazarian SG (2007) Anal Bioanal Chem 389:1525–1532CrossRefGoogle Scholar
  26. 26.
    Dowell FE, Maghirang EB, Fernandez FM, Newton PN, Green MD (2008) J Pharm Biomed Anal 48:1011–1014CrossRefGoogle Scholar
  27. 27.
    de Veij M, Vandenabeele P, Hall KA, Fernandez FM, Green MD, White NJ, Dondorp AM, Newton PN, Moens L (2007) J Raman Spectrosc 38:181–187CrossRefGoogle Scholar
  28. 28.
    Marchand E, Atemnkeng MA, Vanermen S, Plaizier-Vercammen J (2008) Biomed Chromatogr 22:454–459CrossRefGoogle Scholar
  29. 29.
    Gabriels M, Plaizier-Vercammen J (2004) J Chromatogr Sci 42:341–347Google Scholar
  30. 30.
    Agarwal SP, Ali A, Ahuja S (2007) Indian J Pharm Sci 69:841–844CrossRefGoogle Scholar
  31. 31.
    Tayade NG, Nagarsenker MS (2007) J Pharm Biomed Anal 43:839–844CrossRefGoogle Scholar
  32. 32.
    Jahnke RWO (2004) Pharm Ind 66:1187–1193Google Scholar
  33. 33.
    Basco LK (2004) Am J Trop Med Hyg 70:245–250Google Scholar
  34. 34.
    Global Pharma Health Fund (2010) The GPHF-Minilab® - protection against counterfeit medicines. Accessed 7 Feb 2010
  35. 35.
    Ma C, Wang H, Lu X, Xu G, Liu B (2008) J Chromatogr A 1186:412–419CrossRefGoogle Scholar
  36. 36.
    Peng CA, Ferreira JFS, Wood AJ (2006) J Chromatogr A 1133:254–258CrossRefGoogle Scholar
  37. 37.
    Liu S, Tian N, Liu Z, Huang J, Li J, Ferreira JFS (2008) J Chromatogr A 1190:302–306CrossRefGoogle Scholar
  38. 38.
    Liu S, Tian N, Li J, Huang J, Liu Z (2009) Biomed Chromatogr 23:1101–1107CrossRefGoogle Scholar
  39. 39.
    Theoharides AD, Smyth MH, Ashmore RW, Halverson JM, Zhou ZM, Ridder WE, Lin AJ (1988) Anal Chem 60:115–120CrossRefGoogle Scholar
  40. 40.
    Mohamed SS, Khalid SA, Ward SA, Wan TSM, Tang HPO, Zheng M, Haynes RK, Edwards G (1999) J Chromatogr B 731:251–260CrossRefGoogle Scholar
  41. 41.
    Russo R, Guillarme D, Rudaz S, Bicchi C, Veuthey JL (2008) J Sep Sci 31:2377–2387CrossRefGoogle Scholar
  42. 42.
    Ferreira JFS, Gonzalez JM (2009) Phytochem Anal 20:91–97CrossRefGoogle Scholar
  43. 43.
    Souppart C, Gauducheau N, Sandrenan N, Richard F (2002) J Chromatogr B 774:195–203CrossRefGoogle Scholar
  44. 44.
    Naik H, Murry DJ, Kirsch LE, Fleckenstein L (2005) J Chromatogr B 816:233–242CrossRefGoogle Scholar
  45. 45.
    Sabarinath S, Singh RP, Gupta RC (2006) J Chromatogr B 842:36–42CrossRefGoogle Scholar
  46. 46.
    Van Quekelberghe SAA, Soomro SA, Cordonnier JA, Jansen FH (2008) J Anal Toxicol 32:133–139Google Scholar
  47. 47.
    Anderson CA, Drennen JK, Ciurczak EW (2007) In: Burns DA, Ciurzak EW (eds) Handbook of near-infrared analysis. CRC, Boca Raton, pp 585–612Google Scholar
  48. 48.
    Eliasson C, Matousek P (2007) Anal Chem 79:1696–1701CrossRefGoogle Scholar
  49. 49.
    Antalek B (2002) Concepts Magn Res 14:225–258CrossRefGoogle Scholar
  50. 50.
    Trefi S, Gilard V, Balayssac S, Malet-Martino M, Martino R (2008) J Pharm Biomed Anal 46:707–722CrossRefGoogle Scholar
  51. 51.
    Trefi S, Routaboul C, Hamieh S, Gilard V, Malet-Martino M, Martino R (2008) J Pharm Biomed Anal 47:103–113CrossRefGoogle Scholar
  52. 52.
    Trefi S, Gilard V, Balayssac S, Malet-Martino M, Martino R (2009) Magn Reson Chem 47:S163–S173Google Scholar
  53. 53.
    Maurin JK, Plucinski F, Mazurek AP, Fijalek Z (2007) J Pharm Biomed Anal 43:1514–1518CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • R. Martino
    • 1
  • M. Malet-Martino
    • 1
  • V. Gilard
    • 1
  • S. Balayssac
    • 1
  1. 1.Groupe de RMN Biomédicale, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB)Université de Toulouse, UPSToulouse Cedex 9France

Personalised recommendations