Degradation of artemisinin-based combination therapies under tropical conditions
File(s)
Published version
Author(s)
Hall, Zoe
Allan, Elizabeth Louise
van Schalkwyk, Donelly Andrew
van Wyk, Albert
Kaur, Harparkash
Type
Journal Article
Abstract
Poor quality antimalarials, including falsified, substandard, and degraded drugs, are a serious health concern in malaria-endemic countries. Guidelines are lacking on how to distinguish between substandard and degraded drugs. “Forced degradation” in an oven was carried out on three common artemisinin-based combination therapy (ACT) brands to detect products of degradation using liquid chromatography mass spectrometry and help facilitate classification of degraded drugs. “Natural aging” of 2,880 tablets each of ACTs artemether/lumefantrine and artesunate/amodiaquine was undertaken to evaluate their long-term stability in tropical climates. Samples were aged in the presence and absence of light on-site in Ghana and in a stability chamber (London), removed at regular intervals, and analyzed to determine loss of the active pharmaceutical ingredients (APIs) over time and detect products of degradation. Loss of APIs in naturally aged tablets (both in Ghana and the pharmaceutical stability chamber) was 0–7% over 3 years (∼12 months beyond expiry) with low levels of degradation products detected. Using this developed methodology, it was found that a quarter of ACTs purchased in Enugu, Nigeria (concurrent study), that would have been classified as substandard, were in fact degraded. Presence of degradation products together with evidence of insufficient APIs can be used to classify drugs as degraded.
Date Issued
2016-05-04
Date Acceptance
2016-01-13
Citation
The American Journal of Tropical Medicine and Hygiene, 2016, 94 (5), pp.993-1001
ISSN
0002-9637
Publisher
American Society of Tropical Medicine and Hygiene
Start Page
993
End Page
1001
Journal / Book Title
The American Journal of Tropical Medicine and Hygiene
Volume
94
Issue
5
Copyright Statement
© The American Society of Tropical Medicine and Hygiene. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
http://www.ajtmh.org/content/journals/10.4269/ajtmh.15-0665
Subjects
11 Medical and Health Sciences
Tropical Medicine
Publication Status
Published
Date Publish Online
2016-05-04