Volume 75, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


In southeast Asia, the widespread high prevalence of counterfeits tablets of the vital antimalarial artesunate is of great public health concern. To assess the seriousness of this problem, we quantified the amount of active ingredient present in artesunate tablets by liquid chromatography coupled to mass spectrometry. This method, in conjunction with analysis of the packaging, classified tablets as genuine, substandard, or fake and validated results of the colorimetric Fast Red TR test. Eight (35%) of 23 fake artesunate samples contained the wrong active ingredients, which were identified as different erythromycins and paracetamol. Raman spectroscopy identified calcium carbonate as an excipient in 9 (39%) of 23 fake samples. Multivariate unsupervised pattern recognition results indicated two major clusters of artesunate counterfeits, those with counterfeit foil stickers and containing calcium carbonate, erythromycin, and paracetamol, and those with counterfeit holograms and containing starch but without evidence of erythromycin or paracetamol.


Article metrics loading...

Loading full text...

Full text loading...



  1. WHO, 1999. Counterfeit Drugs. Guidelines for the Development of Measures to Combat Counterfeit Drugs. Available from http://www.who.int/medicines/publications/counterfeitguidelines/en/.
  2. O’Brien KL, Selanikio JD, Hecdivert C, Placide MF, Louis M, Barr DB, Barr JR, Hospedales CJ, Lewis MJ, Schwartz B, Philen RM, St Victor S, Espindola J, Needham LL, Denerville K, 1998. Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol poisoning. JAMA 279 : 1175–1180.
  3. Hanif M, Mobarak MR, Ronan A, Rahman D, Donovan JJ, Bennish ML, 1995. Fatal renal-failure caused by diethylene glycol in paracetamol elixir: the Bangladesh epidemic. BMJ 311 : 88–91.
  4. Newton PN, White NJ, Rozendaal JA, Green MD, 2002. Murder by fake drugs: time for international action. BMJ 324 : 800–801.
  5. Cockburn R, Newton PN, Agyarko EK, Akunyili D, White NJ, 2005. The global threat of counterfeit drugs: why industry and governments must communicate the dangers. PLoS Med 2 : 100–106.
  6. Newton P, Proux S, Green M, Smithuis F, Rozendaal J, Prakongpan S, Chotivanich K, Mayxay M, Looareesuwan S, Farrar J, Nosten F, White NJ, 2001. Fake artesunate in southeast Asia. Lancet 357 : 1948–1950.
  7. Newton PN, Green M, Fernandez FM, Day NP, White NJ, 2006. Counterfeit anti-infective drugs. Lancet Infect Dis. 6 : 602–613.
  8. Basco LK, 2004. Molecular epidemiology of malaria in Cameroon. XIX. Quality of antimalarial drugs used for self-medication. Am J Trop Med Hyg 70 : 245–250.
  9. Daviss B, 2005. Malaria, science, and social responsibility. Scientist 19 : 42–43.
  10. White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113 : 1084–1092.
  11. van Agtmael MA, Eggelte TA, van Boxtel CJ, 1999. Artemisinin drugs in the treatment of malaria: From medicinal herb to registered medication. Trends Pharmacol Sci 20 : 199–205.
  12. Aldhous P, 2005. Murder by medicine. Nature 434 : 132–136.
  13. Dondorp AM, Newton PN, Mayxay M, van Damme W, Smithuis FM, Yeung S, Petit A, Lynam AJ, Johnson A, Hien TT, McGready R, Farrar JJ, Looareesuwan S, Day NPJ, Green MD, White NJ, 2004. Fake antimalarials in southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials. Trop Med Int Health 9 : 1241–1246.
  14. Newton PN, Dondorp A, Green M, Mayxay M, White NJ, 2003. Counterfeit artesunate antimalarials in southeast Asia. Lancet 362 : 169.
  15. Newton PN, McGready R, Fernandez FM, Green MD, Sunjio M, Bruneton C, Phanouvong S, Millet P, Whitty CJ, Talisuna AO, Proux S, Christophel EM, Malenga G, Singhasivanon P, Bojang K, Kaur H, Palmer K, Day NPJ, Greenwood BM, Nosten F, White NJ, 2006. Manslaughter by fake artesunate in Asia: will Africa be next? PLoS Med 3 : 1–4.
  16. Green M, Mount DL, Wirtz RA, 2001. Authentication of Artemether, Artesunate and dihydroartemisin antimalarial tablets using a simple colorimetric method. Trop Med Int Health 6 : 980–982.
  17. Lim CK, Lord G, 2002. Current developments in LC-MS for pharmaceutical analysis. Biol Pharm Bull 25 : 547–557.
  18. NIST Scientific and Technical Databases, 2002. Available from http://www.nist.gov/srd/nist1a.htm.
  19. Vankeirsbilck T, Vercauteren A, Baeyens W, Van der Weken G, Verpoort F, Vergote G, Remon JP, 2002. Applications of Raman spectroscopy in pharmaceutical analysis. TrAC Trends Anal Chem 21 : 869–877.
  20. Massart DL, Vandeginste BG, Buydens LM, De Jong S, Lewi PJ, Smeyers-Verbeke J, 1997. Handbook of Chemometrics and Qualimetrics. Amsterdam: Elsevier.
  21. World Health Organization, 2006. What Are Substandard Drugs? Available from http://www.who.int/medicines/services/counterfeit/faqs/06/en/.
  22. Gates P, Kearney G, Jones R, Leadlay P, Staunton J, 1999. Structural elucidation studies of erythromycins by electrospray tandem mass spectrometry. Rapid Commun Mass Spectrom 13 : 242–246.
  23. Wardrop J, Ficker D, Franklin S, Gorski R, 2000. Determination of erythromycin and related substances in enteric-coated tablet formulations by reversed-phase liquid chromatography. J Pharm Sci 89 : 1097–1105.
  24. Allen LV Jr, Popovich NG, Ansel HC, Allen LV, 2004. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lippincott Williams and Wilkins.
  25. Jähnke RW, Küsters G, 2001. Detecting counterfeit drugs-protection against counterfeit medicines using the GPHF-Minilab. Bull Mekong Malaria Forum 8 : 118–124.
  26. Rozendaal J, 2000. Fake antimalarials circulating in Cambodia. Bull Mekong Malaria Forum 7 : 62–68.
  27. United States Pharmacopeia, 2006. Fake Malarials Found in Yunnan Province, China. Available from http://www.uspdqi.org/pubs/other/FakeAntimalarialsinChina.pdf.
  28. Hartl DL, 2004. The origin of malaria: mixed messages from genetic diversity. Nat Rev Microbiol 2 : 15–22.
  29. Fernandez FM, Cody RB, Green M, Hampton CY, McGready R, Sengaloundeth S, White NJ, Newton PN, 2006. Characterization of solid counterfeit drug samples by desorption electro-spray ionization and direct-analysis-in-real-time coupled to time-of-flight mass spectrometry. Chem Med Chem 1 : 702–705.
  30. Wolff JC, Thomson LA, Eckers C, 2003. Identification of the ‘wrong’ active pharmaceutical ingredient in a counterfeit Hal-fan(TM) drug product using accurate mass electrospray ionisation mass spectrometry, accurate mass tandem mass spectrometry and liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom 17 : 215–221.

Data & Media loading...

Supplementary Data

Supplemental information

  • Received : 04 Mar 2006
  • Accepted : 11 Jun 2006

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error