Chemical and Bioassay Techniques to Authenticate Quality of the Anti-Leishmanial Drug Miltefosine.


Kaur, H; Seifert, K; Hawkes, GE; Coumbarides, GS; Alvar, J; Croft, SL; (2015) Chemical and Bioassay Techniques to Authenticate Quality of the Anti-Leishmanial Drug Miltefosine. The American journal of tropical medicine and hygiene, 92 (6 Suppl). pp. 31-8. ISSN 0002-9637 DOI: 10.4269/ajtmh.14-0586

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Abstract

: Miltefosine, an effective oral treatment of visceral leishmaniasis (VL), was selected in May 2005, by the governments of India, Nepal, and Bangladesh for the elimination of VL. However, abnormally high treatment failure rates reported in patients in Bangladesh, given a miltefosine generic product ("Miltefos", Popular Pharmaceuticals Ltd.) during 2008, led the World Health Organization (WHO) to procure this formulation for quality testing. Proton ((1)H) and phosphorous ((31)P) nuclear magnetic resonance (NMR) analyses of the Miltefos™ capsules did not give the peaks defined for Impavido®, the quality assured VL treatment product from Aeterna Zentaris. Contents of capsules of Impavido® yielded expected peaks for miltefosine (m/z 408.33 for the protonated parent ion and m/z 183.99 plus m/z 124.8 the fragment ions) that were absent in the Miltefos™ capsules. Furthermore, testing using an in vitro Leishmania donovani intracellular amastigote-macrophage model, yielded EC50 values of between 2.55 and 4.06 μg/mL and 3.02 to 5.92 μg/mL for extracts from the Impavido® capsules and the miltefosine standard, respectively. Lack of significant anti-leishmanial activity of Miltefos™ capsules was identified in this assay even at concentrations up to 100 μg/mL. Capsules of Miltefos™ were classified as falsified (absence of stated active pharmaceutical ingredient) by three methods-NMR and mass spectrometry analysis and bioassay.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Antimicrobial Resistance Centre (AMR)
Leishmaniasis Group
PubMed ID: 25897058
Web of Science ID: 355785600006
URI: http://researchonline.lshtm.ac.uk/id/eprint/2160258

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