A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia

Paul Newton and colleagues' international, collaborative study found evidence that counterfeit artesunate was being manufactured in China, which prompted a criminal investigation

Characterization of counterfeit artesunate antimalarial tablets from southeast Asia.

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

Fast detection and identification of counterfeit antimalarial tablets by Raman spectroscopy

During the last decade there has been an apparent increase in the prevalence of counterfeit medicines in developing as well as developed countries. The pivotal antimalarial artesunate has been counterfeited on a large scale in SE Asia. In this work, the possibilities of Raman spectroscopy are explored as a fast and reliable screening method for the detection of counterfeit artesunate tablets. In this study, 50 'artesunate tablets', purchased in SE Asia, were examined. This spectroscopic method was able to distinguish between genuine and counterfeit artesunate and to identify the composition of the counterfeit tablets. These contained no detectable levels of artesunate, but consisted mostly of starch, calcite (CaCO3), and paracetamol (4-acetamidophenol). In one particular case an admixture of rutile (TiO2) and artesunate was detected. The results of the investigation by Raman spectroscopy were in agreement with those of colorimetric tests and of liquid chromatography-mass spectrometry on the artesunate. Moreover, principal components analysis (PCA) was combined with hierarchical cluster analysis to establish an automated approach for the discrimination between different groups of counterfeits and genuine artesunate tablets. These results demonstrate that Raman spectroscopy combined with multivariate analysis is a promising and reliable methodology for the fast characterization of genuine and counterfeit artesunate antimalarial tablets. Copyright © 2006 John Wiley and Sons, Ltd

Red blood cells polarize green laser light revealing hemoglobin's enhanced non-fundamental Raman modes

In general, the first overtone modes produce weak bands that appear at approximately twice the wavenumber value of the fundamental transitions in vibrational spectra. Here, we report the existence of a series of enhanced non-fundamental bands in resonance Raman (RR) spectra recorded for hemoglobin (Hb) inside the highly concentrated heme environment of the red blood cell (RBC) by exciting with a 514.5 nm laser line. Such bands are most intense when detecting parallel-polarized light. The enhancement is explained through excitonic theory invoking a type C scattering mechanism and bands have been assigned to overtone and combination bands based on symmetry arguments and polarization measurements. By using malaria diagnosis as an example, we demonstrate that combining the non-fundamental and fundamental regions of the RR spectrum improves the sensitivity and diagnostic capability of the technique. The discovery will have considerable implications for the ongoing development of Raman spectroscopy for blood disease diagnoses and monitoring heme perturbation in response to environmental stimuli

Poor quality drugs: grand challenges in high throughput detection, countrywide sampling, and forensics in developing countries.

Throughout history, poor quality medicines have been a persistent problem, with periodical crises in the supply of antimicrobials, such as fake cinchona bark in the 1600s and fake quinine in the 1800s. Regrettably, this problem seems to have grown in the last decade, especially afflicting unsuspecting patients and those seeking medicines via on-line pharmacies. Here we discuss some of the challenges related to the fight against poor quality drugs, and counterfeits in particular, with an emphasis on the analytical tools available, their relative performance, and the necessary workflows needed for distinguishing between genuine, substandard, degraded and counterfeit medicines

Resonance Raman and UV-Visible Microscopy Reveals that Conditioning Red Blood Cells with Repeated Doses of Sodium Dithionite Increases Haemoglobin Oxygen Uptake

Here we report that successive additions of fresh dithionite to a suspension of red blood cells (RBCs) increase the capacity of the cells to uptake oxygen. This effect was not observed when the RBCs were similarly preconditioned using gaseous N2 to induce short episodes of hypoxia. The effect of successive sodium dithionite and N2 gas additions on a population of functional erythrocytes was monitored using Raman confocal microscopy, with 514 nm excitation, and UV–visible microscopy. The results indicate that successive additions of sodium dithionite in a suspension of red blood cells leads to an increase in both the rate and the capacity of the RBCs to uptake oxygen. The sodium dithionite did not cause haemoglobin from lysed RBCs to uptake more oxygen after successive additions and hence this effect was only observed in functional intact RBCs. Experiments performed with polarised Raman spectroscopy suggest that sodium dithionite increases the disorder of Hb in the RBC facilitating oxygen diffusion