ATR-FTIR spectroscopy and chemometrics: An interesting tool to discriminate and characterize counterfeit medicines

Abstract

Counterfeit medicines pose a huge threat to public health worldwide. High amounts of counterfeit pharmaceuticals enter the European market and therefore detection of these products is essential. Attenuated Total Reflection Fourier-Transform infrared spectroscopy (ATR-FTIR) might be useful for the screening of counterfeit medicines since it is easy to use and little sample preparation is required. Furthermore, this approach might be helpful to customs to obtain a first evaluation of suspected samples. This study proposes a combination of ATR-FTIR and chemometrics to discriminate and classify counterfeit medicines. A sample set, containing 209 samples in total, was analyzed using ATR-FTIR and the obtained spectra were used as fingerprints in the chemometric data-analysis which included Principal Component Analysis (PCA), k-Nearest Neighbours (k-NN), Classification and Regression Trees (CART) and Soft Independent Modelling of Class Analogy (SIMCA). First it was verified whether the mentioned techniques are capable to distinguish samples containing different active pharmaceutical ingredients (APIs). PCA showed a clear tendency of discrimination based on the API present; k-NN, CART and SIMCA were capable to create suitable prediction models based on the presence of different APIs. However k-NN performs the least while SIMCA performs the best. Secondly, it was tested whether these three models could be expanded to discriminate between genuine and counterfeit samples as well. k-NN was not able to make the desired discrimination and therefore it was not useful. CART performed better but also this model was less suited. SIMCA, on the other hand, resulted in a model with a 100% correct discrimination between genuine and counterfeit drugs. This study shows that chemometric analysis of ATR-FTIR fingerprints is a valuable tool to discriminate genuine from counterfeit samples and to classify counterfeit medicines.

ATR-FTIR characterization of generic brand-named and counterfeit sildenafil- and tadalafil-based tablets found on the Brazilian market

“…Although several studies based on infrared profiling [12,[14][15][16][17][18][19][20] have been published over this decade concerning identification of counterfeit samples of Viagra and Cialis, most of these works do not consider nor discuss the compositional characteristics of the samples, employing spectral profiling mostly as a data source for chemometrical analysis, an approach which, although very powerful and useful, is usually beyond practical use in most forensic laboratories. The present approach was based on more direct and comparative practical analyses of the spectral profiles of tablet cores, applied not only to identify the AI of each tablet, but also the major excipients/adjuvants present.…”

Detection of Counterfeit Durateston® Using Fourier Transform Infrared Spectroscopy and Partial Least Squares - Discriminant Analysis

“…PCA is an exploratory tool to detect tendencies in a group of samples, showing which characteristics can be used for class separation, 19 and it was possible to visualize all subgroups in this study using this tool ( Figure 4B). However, since forensic results demand a high level of statistical certainty to be issued, and to avoid the visual/ subjective interpretation of the PCA score plot, PLS-DA was used to develop a method that could be implemented as a routine analysis and yield results for which confidence limits could be estimated.…”

“…Sacré et al 13 achieved similar result by combining FTIR and NIR or FTIR and Raman spectroscopy associated with PLS analysis for Viagra-like and Cialis-like samples, respectively. For the same products, Custers et al 19 achieved a 90.5% performance when discriminating genuine and counterfeit samples using FTIR and SIMCA.…”

“…[8][9][10][11][12] Spectroscopic techniques such as Raman, near infrared, and Fourier transform infrared (FTIR), together with chemometric tools, are being successfully used to analyze suspected counterfeit medicines. [13][14][15][16][17][18][19] They have the advantage of being less time-consuming than chromatographic methods, with little or no sample preparation. [13][14][15]19 However, to the best of our knowledge, only one work using spectroscopic methods to analyze anabolic steroid medicines has been published so far, describing the investigation of the composition of methandrostenolone-containing tablets by near infrared and Raman spectroscopy.…”

“…[13][14][15][16][17][18][19] They have the advantage of being less time-consuming than chromatographic methods, with little or no sample preparation. [13][14][15]19 However, to the best of our knowledge, only one work using spectroscopic methods to analyze anabolic steroid medicines has been published so far, describing the investigation of the composition of methandrostenolone-containing tablets by near infrared and Raman spectroscopy. 20 The aim of this work was to develop a simple, fast, low-cost and reliable method for the detection of Durateston ® counterfeits using FTIR and partial least squares -discriminant analysis (PLS-DA).…”