Editorial Feature

Identifying Drugs in Packaging Using Spectroscopy

Raman spectroscopy has been used with some success to detect drug molecules within white plastic containers. Now, researchers at Shizuoka University in Japan have found a way to use an attenuated total reflection version of terahertz spectroscopy to identify drugs in plastic packaging even for compounds with high terahertz absorption.

drug spectroscopy

Image Credit: Irina Devaeva/Shutterstock.com

One of the advantages of spectroscopy for forensic analysis is the ability to use wavelengths that can ‘see inside’ objects. In art history and restoration, shortwave infrared light is used to peer under layers of paint to reveal hidden paintings or sketches underneath, without damaging the surface layer. For art and historical applications, the non-destructive nature of the analysis is crucial, as is the lack of need for any sample preparation.

With the right choice of wavelength, spectroscopic methods can be used to look inside packaging without the need to open it. The ability to perform chemical analysis of pharmaceuticals without opening the packaging is useful for quality control in the pharmaceutical industry as well as drug testing and forensic analysis of samples.

Conventional visible Raman spectroscopy struggles with opaque containers as the material scatters the laser light making the weak backscattered Raman signal nearly impossible to detect. Spatially offset Raman methods can circumvent the scattering issue by using a series of gating techniques and collecting the Raman signal from a region away from the laser illumination zone.

However, even for methods like spatially offset Raman spectroscopy, one of the key challenges in looking for drug molecules inside plastic packaging is that the packaging has its own spectrum which may overlap and obscure the spectral response of the drug. Multivariate analysis methods go some way to solving this but another approach is to use electromagnetic radiation to which the plastic casing is more transparent.

Terahertz Spectroscopy

The terahertz region covers approximately 0.3 to 3 Terahertz. This is the frequency range that is between the infrared and microwave regions and is of great interest for many sensing applications as many common non-metallic materials, such as fabrics and plastics, are transparent to terahertz radiation.

While the lack of interference or absorption by the packaging would have clear advantages for sensing and imaging applications, one of the challenges with developing terahertz spectroscopies has been the relative underdevelopment of terahertz sources, detectors and optics.

To harness the power of terahertz sensing and imaging, there has been a recent wealth of development in the area of terahertz technologies that have led to the application of terahertz radiation in a number of areas, including food safety. While there is still a need for more cost-effective technologies, the ability to scan foodstuffs in a variety of packaging types without the need to remove them and the wealth of spectral information that can be obtained means that the methodology has a clear appeal for identifying properties such as food quality and adulteration.

Transmission and Reflection

Many spectroscopic techniques are performed in a transmission geometry – where the light passes through the sample of interest and the attenuation of the detected light is measured. The detected light levels are then used to work out how much the sample has absorbed and this can be translated into knowledge about the molecular structure.

Absorption measurements are not suitable for all sample types. It is impossible to detect light passing through very dense or strongly absorbing samples. Instead, to recover similar information as from a transmission measurement, the spectroscopy can be performed in a reflective geometry, where the light from the surface that is reflected is detected instead.

Attenuated total reflection is one such reflection method commonly used with infrared spectroscopy but can be extended to the terahertz regime as well. The sample is placed on a prism so that the incident light undergoes total internal reflection. As well as this, an evanescent wave is created at the interface between the sample and prism that can be used to probe the properties of the system of interest.

Drug Detection

By combining the attenuated total reflection approach with time-domain signal recording, the team recorded the terahertz spectra of samples within the packaging that did absorb some terahertz radiation. The team detected a lactose sample within a thin polythene bag and successfully identified the compound based on its spectral fingerprint.

The advantage of the new approach is that it can be used on samples of any thickness and, as the penetration depth of the radiation is wavelength-dependent, the team could potentially also tune the wavelength of the terahertz radiation for thicker plastic bags.

Mistakes in the dispensing process at a pharmacy can have serious consequences and the ability to record a spectrum of samples within medicine bags in a straightforward way with an analysis procedure that is easy to automate could help create standard screening procedures to identify potential dispensing mistakes. The team says its approach still needs to be tested on a wider variety of fabrics, but this is an important step in measuring the terahertz spectra of strongly absorbing species.

References and Further Reading

Hargreaves, M. D. (2006). Handheld Raman spectrometers and their applications. Encyclopedia of Analytical Chemistry: Applications, Theory and Instrumentation, 1-16. https://doi.org/10.1002/9780470027318.a9378

Wu, T., Li, G., Yang, Z., Zhang, H., Lei, Y., Wang, N., & Zhang, L. (2017). Shortwave Infrared Imaging Spectroscopy for Analysis of Ancient Paintings. Appl. Spectrosc., 71(5), 977–987. http://opg.optica.org/as/abstract.cfm?URI=as-71-5-977

Hargreaves, M. D. (2006). Handheld Raman spectrometers and their applications. Encyclopedia of Analytical Chemistry: Applications, Theory and Instrumentation, 1-16. https://doi.org/10.1002/9780470027318.a9378

Matousek, P., Clark, I. P., Draper, E. R. C., Morris, M. D., Goodship, A. E., Everall, N., Towrie, M., Finney, W. F., & Parker, A. W. (2005). Subsurface Probing in Diffusely Scattering Media Using Spatially Offset Raman Spectroscopy. Applied Spectroscopy, 59(4), 393–400.

Chan, W. L., Deibel, J., & Mittleman, D. M. (2007). Imaging with terahertz radiation. Reports on Progress in Physics, 70, 1325–1379. https://doi.org/10.1088/0034-4885/70/8/R02

Feng, C., & Otani, C. (2021). Terahertz spectroscopy technology as an innovative technique for food : Current state-of- the-Art research advances. Critical Reviews in Food Science and Nutrition, 61(15), 2523–2543. https://doi.org/10.1080/10408398.2020.1779649

Hashimoto, K., & Tripathi, S. R. (2022). Non-Destructive Identification of Drugs. Plastic Packaging Using Attenuated Total Reflection Terahertz Time Domain Spectroscopy. 99–106.

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Rebecca Ingle, Ph.D

Written by

Rebecca Ingle, Ph.D

Dr. Rebecca Ingle is a researcher in the field of ultrafast spectroscopy, where she specializes in using X-ray and optical spectroscopies to track precisely what happens during light-triggered chemical reactions.


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