Counterfeit pharmaceuticals are a serious problem across the world and include products comprising potentially unsafe substances and products containing zero or diluted quantities of active pharmaceutical ingredients (API). Although the current scope of this issue is not known, nearly 10% of the pharmaceuticals available in the global supply chain are counterfeit, according to the World Health Organization.
Besides posing health and safety concerns, counterfeits will also lead to revenue loss to pharmaceutical companies worldwide. Counterfeit not only targets lifestyle drugs such as weight-loss or impotence but also lifesaving treatments such as antimalarial or even anti-cancer medication are recently being targeted.
Out-of-laboratory analysis for authenticating pharmaceuticals and other products has made possible thanks to instrument miniaturization. Raman spectroscopy is suitable for identifying pharmaceuticals because of its chemical selectivity and it is widely used in the detection of counterfeit drugs. Portable Raman devices fitted with laser excitation at 785 nm are commonly available.
In this article, a Xantus-2 portable Raman spectrometer equipped with 1064 nm laser from Rigaku Raman Technologies is compared with a competitive system equipped with a 785 nm laser excitation. Rigaku's Xantus-2-785/1064 dual wavelength spectrometer with a sample vial holder is depicted in Figure 1.
Figure 1. Rigaku's Xantus-2-785/1064 Dual Wavelength Spectrometer with Sample Vial Holder.
Samples were analyzed either on a Rigaku Xantus -2 Dual instrument (Micro 2020 software, version 2.fc2.0.4) or on a competitive system featuring a 785 nm laser. A laser power of 300 mW with auto-exposure was used in all cases and exposure times were typically 1000 ms.
Sample Preparation and Experimental Procedure
Samples of authentic and counterfeit tablets and capsule types used in this analysis included Viagra (Sildenafil Citrate) and Alii (Orlistat). Alii capsule blends were fed into a vial and then directly measured with the Rigaku Xantus -2 Raman at 1064 nm laser excitation and with the competitive system at 785 nm excitation. The measurement of Viagra tablets was performed ‘as is’ through the coating on both devices.
All spectra were observed in the optimal finger print region of 300 to 1650 cm-1. In all cases, excitation at 785 nm resulted in a powerful fluorescence background preventing comparison of counterfeit and authentic products. On the other hand, fluorescence interference was not observed with 1064 nm excitation. Utility of the Xantus-2 Raman (1064 nm laser) is illustrated in Figure 2.
Figure 2. Authentic Alii spectra acquired at 785 nm excitation (red trace) and 1064 nm excitation (blue trace = authentic and green trace = counterfeit).
Fluorescence interference makes all usable spectral data unclear when excited with 785 nm laser, while spectra acquired at 1064 nm easily differentiate between authentic and counterfeit Alii products. Authentic Viagra measured at both 785 and 1064 nm excitation is shown in Figure 3.
Figure 3. Authentic Viagra spectra acquired at 785 nm (red trace) and 1064 nm excitation (blue trace = authentic and green trace = counterfeit).
Titanium dioxide bands from the counterfeit and authentic Viagra were seen at 785 nm excitation, but superimposed with a broad fluorescence background, which makes the data unclear. Only 1064 nm excitation clearly differentiates between counterfeit and authentic products. Spectral data from the tablet coating material, Opadry Blue as well as the API, Sildenafil Citrate, were visible in Raman spectra acquired from the coated Viagra sample.
Figure 4. Viagra coated and core spectra acquired at 1064 nm n (red and blue traces) along with the Opadry Blue (green trace). API bands are labeled.
The comparison of the spectra acquired from the coated tablet and those obtained from the core of the tablet and pure Opadry Blue shows that the 1064 nm Raman excitation is able to make the measurements of the tablet core through the coating, as depicted in Figure 4. This degree of determining data was not visible in data acquired utilizing 785 nm excitation.
In several cases, 785 nm Raman excitation results in fluorescence interference that can prevent the application of Raman as an analytical instrument to detect counterfeit. On the other hand, Raman data obtained with 1064 nm excitation can yield fluorescence free, chemically specific data.
This information has been sourced, reviewed and adapted from materials provided by Rigaku Raman.
For more information on this source, please visit Rigaku Analytical Devices.