title: Degradation of Artemisinin-Based Combination Therapies Under Tropical Conditions.
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.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Hall
authors.forename: Elizabeth Louise
authors.initials: EL
authors.lastname: Allan
authors.forename: Donelly Andrew
authors.initials: DA
authors.lastname: van Schalkwyk
authors.forename: Albert
authors.initials: A
authors.lastname: van Wyk
authors.forename: Harparkash
authors.initials: H
authors.lastname: Kaur
mesh_terms: D000962:Antimalarials / Q000737:chemistry*; D037621:Artemisinins / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D006358:Hot Temperature; D013997:Time Factors; D014329:Tropical Climate
chemical_list: D000962:Antimalarials; D037621:Artemisinins