Discovery of miltefosine fakes highlights need for simple assays

The discovery of counterfeit generic miltefosine capsules for the treatment of visceral leishmaniasis serves to underscore the urgent need for simple, inexpensive assays to evaluate medicines quality in the field, according to a new study published in the Royal Society of Chemistry journal Analyst.

Following reports of abnormally high failure rates in hundreds of Bangladeshi patients being treated for the neglected disease, researchers from the University of Amsterdam obtained and tested samples of the locally procured miltefosine capsules that had been administered. The researchers analysed two batches of the drug, called Miltefos 50 and Miltefos 10, which had corresponding label claims of 50mg and 10mg miltefosine, respectively.

Using the following analytical techniques, the researchers assessed the Miltefos samples to establish pharmaceutical equivalency to the genuine product, Impavido:

•    Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)
•    Fourier-transform infrared (FT-IR) spectrophotometry
•    Near-red infrared (NIR) spectrophotometry
•    A simple, rapid and inexpensive colorimetric miltefosine test developed in the lab

The researchers note that the diverse set of analytical chemical techniques helped to detect and identify miltefosine, both qualitatively and quantitatively, in pharmaceutical preparations. Using these complementary techniques, they also found that neither of the Miltefos batches contained miltefosine, in contrast to the Impavido.

Characterisation of the Miltefos capsules by LC-MS/MS, FT-IR and NIR revealed the presence of two excipients – lactose and microcrystalline cellulose – but the tests could not demonstrate or identify any other active pharmaceutical ingredient.

Interestingly, the researchers successfully demonstrated the application of their colorimetric miltefosine test and its suitability for use in the field. As with the other techniques, the colorimetric test showed that it could also be used semi-quantitatively, enabling the identification of drugs containing subtherapeutic quantities of miltefosine.

As a result, the researchers conclude that their simple test could be “very useful for application in the field without the need for extensive laboratory equipment which is particularly practical in resource-poor settings”.