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Published on 1 November 2004

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Techniques to identify counterfeit medicines

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Nicola Wilson
BPharm MSc PhD MRPharmS
Maplethorpe Postdoctoral Fellow
Centre for Pharmaceutical Analysis
London School of Pharmacy
London
UK
E:nic.wilson@ulsop.ac.uk
Work carried out at the Centre for Pharmaceutical Analysis has been supported in the form of a University of London Maplethorpe Fellowship. This work has been carried out with the collaboration of the MHRA and Pfizer.

This article looks at the use of near-infrared (NIR) spectroscopy and near-infrared microscopy as an aid to detect counterfeit medicines, and specifically their use to date in the detection of counterfeit Viagra (sildenafil) at the Centre for Pharmaceutical Analysis, London School of Pharmacy (UK). Medicines seized by authorities such as the Medicines and Healthcare products Regulatory Agency (MHRA) and suspected of being counterfeits are tested at the MHRA’s medicines testing facility in Middlesex. In addition, licensed medicines are routinely sampled and tested there.

Techniques such as high-performance liquid chromatography (HPLC), gas chromatography (GC) and mass spectrometry (MS) are employed, although it is also important to use simple methods such as visual inspection of the product and its packaging. Weighing of tablets is also extremely useful. Many counterfeits tablets are now very sophisticated, and visual detection is becoming increasingly difficult. The increasing sophistication of counterfeiting means that fake tablets may actually contain the correct amount of active ingredient, and a conventional test for active content would be insufficient. It is therefore also important to identify the tablet excipients, as those found in counterfeit tablets are often cheaper, fewer in number and less sophisticated than those found in authentic medicines.

NIR spectroscopy and microscopy have distinct advantages that will be of help in the fight against counterfeit medicines. NIR spectroscopy has been used for many years in the agricultural and dairy industries and has more recently become widely used in the pharmaceutical industry for many purposes, including identification and quality control of active pharmaceutical ingredients (APIs) and excipients, and content uniformity testing. Its advantage is that it requires little or no sample preparation (for example, whole tablets can be analysed), and, once a database has been set up and a method developed, it can give rapid confirmation or otherwise as to a product’s veracity. It is hoped that portable instruments can be used in the future by agencies such as the MHRA or Customs and Excise.

NIR microscopy has the potential to identify not only the API but also the excipients, and to display the distribution of these excipients within the tablet and give an approximation of their percentage content. This could be a useful tool in the comparison and tracking of counterfeit medicines seized at various locations.

The theory
Light in the near-infrared region of the electromagnetic spectrum (approximately 1,100–2,500nm) is directed onto a sample. Depending on the chemical composition of the sample, light of varying wavelengths is absorbed by the sample, and the associated energy is used to cause vibration of the chemical bonds present. A spectrum is obtained, which is a measure of absorbance against wavelength and is representative of the sample as a whole (a “macroscale” technique). NIR spectroscopy can be used on powders, solids and liquids.

NIR microscopy, a more recent technique, works on the same principle, but a tiny beam of NIR light is directed onto the sample, covering only a very small area of a tablet cross-section (a “microscale” technique). In this way, an image map consisting of many hundreds of NIR spectra can be built up. Because these areas (pixels) are so small (30mm2), individual particles can be identified within a sample.

Data analysis
NIR methods of analysis are database-based; that is, libraries containing known spectra are compiled, and incoming sample spectra are compared with those present in the library.

In the case of NIR spectroscopy, the library will contain spectra of authentic samples of the medicinal product to be studied. In the case of NIR microscopy, the library will contain spectra of pure compounds known to be present in the sample (API and excipients) and other chemicals likely to be present in a counterfeit tablet.

Current research
It has previously been demonstrated that NIR spectroscopy can be used to detect counterfeit Viagra, and, in fact, the technique is sufficiently sensitive that it can also distinguish between tablets made at different manufacturing sites.(1)

A NIR microscopy method is currently being developed that can distinguish between authentic and counterfeit tablets, suggest the identity of other components present and show their distribution within the tablet. Samples of known authentic and known counterfeit Viagra were studied, along with generic versions (eg, Kamagra, Caverta, Silagra) and Viagra obtained over the internet (see Figure 1). Generic versions were included in the study, as they should contain the same amount of API but contain different excipients. Images were stored in a database and compared.

[[HPE17_fig1_89]]

Using this new technique, approximately half of the samples obtained over the internet appeared to be counterfeit. These suspect tablets have since been identified as counterfeits by Pfizer using conventional techniques. These suspected counterfeits and the known counterfeits were found to contain other excipients, such as lactose and starch, which are not present in the authentic Viagra tablet bulk. The majority of the counterfeits contained substantially less API than the authentic Viagra. Figure 2 shows the distribution of sildenafil citrate in authentic, counterfeit, generic and internet Viagra samples; nonauthentic Viagra samples and generic versions show a greater “clumping” of the API.

[[HPE17_fig2_90]]

As anyone who has had to contend with junk emails advertising websites supplying Viagra will know, the selling of this “lifestyle” drug is big business, but current research suggests that the public is taking a gamble on ordering medicines over the internet. Notwithstanding the fact that counterfeit drugs may contain substances that are toxic, it is also likely that they will not be effective and could mean the difference between life and death in the case of products such as anticancer treatments. New analysis techniques that can help in the fight against the counterfeit drug trade should therefore be welcomed.

Reference

  1. Yoon WL, Jee RD, Charvill A, et al. Application of near-infrared spectroscopy to the determination of the sites of manufacture of proprietary products. J Pharmaceut Biomed 2004;34:933-44.

Resources
Centre for Pharmaceutical Analysis
School of Pharmacy University of London
W:www.ulsop.ac.uk/depts/pharmchem/pharm_analysis.html
Medicines and Healthcare Products Regulatory Agency
W:www.mhra.gov.uk
International Council for Near Infrared Spectroscopy
W:www.icnirs.org



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