Abstract
BackgroundArtemisinin-based combination therapy (ACT) plays an indispensable role in malaria control and elimination. However, the circulation of counterfeit, substandard drugs has greatly threatened malaria elimination campaigns. Most methods for the analysis of artemisinin and its derivatives require expensive equipment and sophisticated instrumentation. A convenient, easy-to-use diagnostic device for rapid evaluation of the quality of artemisinin drugs at the point-of-care is still lacking. In this study a lateral flow dipstick immunoassay was developed for qualitative and semi-quantitative analysis of artesunate (ATS) and dihydroartemisinin (DHA) in anti-malarial drugs.MethodsThis assay was based on a monoclonal antibody (mAb) raised against ATS. ATS-bovine serum albumin and goat anti-mouse IgG, used as the test capture reagent and the control capture reagent, were coated on the nitrocellulose membrane to form the test line and control line, respectively. The conjugate pad was saturated with the gold-labelled anti-ATS mAb.ResultsThe indicator range of the dipsticks, defined as lowest concentration of the target analytes between which the test line was not visible, were 100-200 and 200-500 ng mL-1 for ATS and DHA, respectively. No competitive inhibition was observed up to 5,000 ng mL-1 of quinine, chloroquine diphosphate salt, primaquine phosphate, pyrimethamine, lumefantrine, amodiaquine, piperaquine tetraphosphate tetrahydrate or pyronaridine tetraphosphate. Semi-quantitative analysis of ATS and DHA in commercial drugs and raw drug materials with the dipsticks produced result agreeable with those determined by high performance liquid chromatography (HPLC). Storage test showed that the indicator range for artemisinins remained unchanged after a week at 37°C and increased four-folds after six months of storage at 4°C or ambient temperature.ConclusionsThe new selected mAb 3D82G7 with high avidity and broad cross reactivity for artemisinins was used to develop and optimize a dipstick immunoassay for qualitative and semi-quantitative analysis of ATS and DHA in anti-malarial drugs. The semi-quantitative analysis of ATS and DHA in commercial drugs and raw drug materials, and the specificity test of the artemisinin-related drugs both proved the accurate performance of the developed dipsticks for semi-quantitation of ACT samples. The dipstick may be used as a point-of-care device for identifying substandard and counterfeit ATS- and DHA-containing anti-malarial drugs.
Highlights
Artemisinin-based combination therapy (ACT) plays an indispensable role in malaria control and elimination
Given that malaria-endemic populations are very familiar with the dipstick-type of malaria rapid diagnostic tests, the aim of this study is to develop a lateral flow dipstick for qualitative and semi-quantitative detection of artemisinins in anti-malarial drugs
The monoclonal antibody (mAb) with a high titer and showing broad cross reactivity against artemisinin derivatives was selected for dipstick development
Summary
Artemisinin-based combination therapy (ACT) plays an indispensable role in malaria control and elimination. The circulation of counterfeit, substandard drugs has greatly threatened malaria elimination campaigns. Counterfeit and substandard drugs greatly threaten malaria elimination campaigns. This problem is widespread in resource-poor developing countries [1]. A survey conducted in 2006 in Thailand revealed that 15.4% of artesunate (ATS), 11.1% of chloroquine, and 29.4% of quinine were substandard [7] While this problem is serious in some Southeast Asian countries, some African countries, where malaria is most prevalent, may be worrisome. A recent review of anti-malarial drug qualities in Southeast Asia and sub-Saharan Africa, which shows that at least 35% of the anti-malarials failed the chemical analysis and large proportions of them as counterfeit drugs, clearly underline the severity of the fake and substandard anti-malarial drug situation [10]
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