Solving composition of falsified artemether/lumefantrine formulation by hyperspectral imaging

The emerging internet trade and its potential significant profitability cause falsified drugs to be one of the major public health issues of the 21st century. Although some preventing measures - such as the new European Parliament Directive 2011/62/UE - have been taken during the last decade, drugs are subject to more frequent monitoring from the authorities. New techniques thus have to be developed in order to help them investigate the relationships between falsified drugs and industries.
Some preliminary tests such as visual inspection or colorimetric testing can be performed in order to check drug authenticity. When these tests are inconclusive, spectroscopy and hyperspectral imaging can be used to provide more information, especially to characterize the composition of presumed falsified samples. The efficiency of this technique has no longer to be proven. Vibrational hyperspectral imaging has many advantages such as the non-destruction of the sample and the possibility to combine spectral and spatial information. Once obtained, the hyperspectral data may be decomposed in its various spectral (qualitative) and spatial (quantitative) components using resolution algorithms such as MCR-ALS. The resolution of the spectral component allows the elucidation of the complete formulation composition without a priori knowledge, including mineral and organic compounds. This composition may be used as a production fingerprint for further forensic investigations.
In this study, six artemether/lumefantrine formulations (two batches of Combiart 20/120 and four batches of Coartem 20/120) have been analyzed for falsification suspicion. First, a handheld Raman spectroscopic analysis has been performed confirming the falsification. The analysis confirmed the supposed absence of active compounds. In order to complete the knowledge of the formulations, one tablet per sample has been further analyzed by hyperspectral imaging. The MCR-ALS decomposition of the hyperspectral data cube shows that five out of the six samples (2 Combiart and 3 Coartem) have the same composition. Those samples are composed by two active compounds: sildenafil and ciprofloxacine chlorhydrate monohydrate at traces level by same excipients (organic and inorganic). This finding seems to indicate that despite different brand names, packaging and tablet shapes, these samples come from the same production.