Research Critique

Research Critique

Background of the publication

Since the late 1990s, counterfeit drugs manufactured to mimic antimalarial medicines have been detected in increasing numbers. Each year, 300-500 million people in Asia and Africa contract Plasmodium falciparum malaria and approximately 1.5 million die. The control of malaria, which is dependent on effective antimalarial drugs and bed nets, has been severely hampered by a widespread increase in the prevalence of drug-resistant malaria parasites. Artesunate, an artemisinin derivative, is widely and increasingly used in the treatment of P. falciparum malaria in many southeast Asian and African countries and is vital for the therapy of drug-resistant malaria. In Asia, artesunate has become the target of an extremely sophisticated and prolific counterfeit drug trade that includes the counterfeiting of both the artesunate tablets and packaging, which look extremely similar to the authentic product. In response to this public health problem, Green and others developed a colorimetric Fast Red TR dye test16 that rapidly and inexpensively screens for the presence of artemisinin-derived compounds such as artemether, artesunate, and dihydroartemisinin in tablets. There are at least 10 different manufacturers of artesunate tablets in Asia. The tablets produced by them have a stated artesunate content of 50 mg. Surveys conducted in 1999-2000 and 2001-2002 in Cambodia, Lao People's Democratic Republic (Laos), Burma (Myanmar), on the Thailand/Burma border, and Vietnam demonstrated that 38% and 53%, respectively, of artesunate tablets contained no active ingredient. To date, only artesunate labeled as made by Guilin Pharmaceutical Co., Ltd. (Guilin, Guangxi, People's Republic of China) has been found to be counterfeit. Visual inspection, including the examination of the holograms, bar codes, printing, crimping, color, size, weight, and consistency of the putative artesunate tablets, was in good agreement with the colorimetric test results in the first survey, but not in the second survey. The counterfeiters appear to have responded to the increase in public awareness by producing more sophisticated counterfeit holograms and packaging, making it very difficult to distinguish the counterfeit and genuine drugs.

Basic Theory of instrument used to collect data

Raman spectroscopy provides specific information on the identification of analytes, characterization of sample matrices, and molecular spectroscopic information useful in the structural elucidation of unknowns. The technique is rapid and when coupled with sample preparation methodologies (i.e., micro-extractions, fraction collections, small particle analysis), a large amount of information can be obtained from a single piece of forensic evidence.  This research uses liquid chromatography-mass spectrometry (LC-MS) method to quantitatively evaluate the contents of artesunate tablets, to validate the Fast Red TR colorimetric test results, and to investigate the presence of other active ingredients. Raman spectroscopy was used to characterize the excipients present in the tablets and complement the LC-MS analysis. We then used multivariate pattern recognition methods to examine the chemical similarities and differences between the chemical fingerprints of different types of fake tablets, and to correlate these similarities with packaging characteristics and sample origin.

A major difference between traditional HPLC and the chromatography used in LC-MS is that in the latter case the scale is usually much smaller, both with respect to ...