Rapid Screening Methods to Identify Substandard and Falsified Medicines
Substandard and falsified medicines (SF) are a major global public health problem and occur throughout healthcare systems worldwide. With an average occurrence of 10% of all medicines globally, the specific levels range from ~1% of all medicines in high-income countries (HIC) to as much as 30-40% in low-income countries (LIC) and low-middle income countries (LMIC). Current detection methods for SF medicines range from ‘low tech’ approaches, for example, visual appearance, thin layer chromatography (TLC) to those that are technically refined, such as, Raman spectroscopy, Near Infrared (NIR) spectroscopy and Mass Spectrometry (MS). In order to counteract the increasing complexity of anti-counterfeit measures, counterfeiters are finding ever more sophisticated ways to bypass existing screening techniques. Therefore, the aim of this research is to develop a novel rapid screening method to identify SF medicines. The performance of seven different benchtop instruments has been investigated with respect to their potential to deliver rapid assessment of the identity and to quantify the level of Active Pharmaceutical Ingredient’s (API’s) present in tablet samples. The materials used in this research comprised of 29 reference samples and 64 individual group samples from 8 countries, totaling some 867 tablets. Tablets were analysed in both whole and powdered forms. Mass Spectrometry provided the least complex data, followed by Raman and then Attenuated Total Reflectance Fourier Transform Infrared (ATR FTIR). The mass spectrometer was the least reliable instrument, but provided the greatest sensitivity. Successful identification of the API was obtained from ATR FTIR and Raman analysis and from Direct Insertion Probe (DIP) Mass Spectrometry. Quantitative levels of API could be obtained from Ultraviolet (UV) and ATR FTIR measurements, whilst some excipient levels could be determined by Elemental Dispersive X-ray (EDX) spectroscopy. Handheld Raman systems produced some erroneous quantitative information. The majority of samples examined were within ±10% of the stated level, as per the British Pharmacopeia specifications; however, there was some evidence of substandard medication. Substandard medication was suspected in 2 of the 64 pharmaceutical products assessed. At the present state of development, the Raman and ATR FTIR equipment could be used in LMIC’s for the screening of tablet samples. PCA in conjunction with Raman spectroscopy identified an anomalous sample in a set of proprietary preparations from different countries. A combination of the techniques cited confirmed the inclusion of a non-standard excipients into this formulation.
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