TY - JOUR
T1 - Development of monoclonal antibody-based immunoassays for quantification and rapid assessment of dihydroartemisinin contents in antimalarial drugs
AU - Ning, Xiangxue
AU - Li, Weizhi
AU - Wang, Mian
AU - Guo, Suqin
AU - Tan, Guiyu
AU - Wang, Baomin
AU - Cui, Liwang
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health ( U19AI089672 ).
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/9/10
Y1 - 2018/9/10
N2 - Dihydroartemisinin (DHA) is one of the artemisinin derivatives widely used in artemisinin-based combination therapies (ACTs) for malaria treatment. The availability of a point-of-care device for estimation of DHA quantity would allow a quick quality assessment of the DHA-containing drugs. In this study, 9-O-succinylartemisinin was obtained from microbial fermentation of artemisinin, which was hydrogenated to 9-O-succinyldihydroartemisinin as the hapten for DHA. A monoclonal antibody (mAb), designated as 2G11G4, was identified after screening the hybridoma library, which showed 52.3% cross reactivity to artemisinin, but low or no cross reactivity to artesunate, artemether, and several ACTs partner drugs. Based on this mAb, a highly-sensitive, indirect competitive enzyme-linked immunosorbent assay was designed, which showed 50% inhibition concentration of DHA at 1.16 ng/mL, a working range of 0.26–4.87 ng/mL, and limit of detection of 0.18 ng/mL. In addition, a colloidal gold-based lateral flow immunoassay (dipstick) was developed with an indicator range (indicating sensitivity) of 50–100 ng/mL. This dipstick was evaluated for determination of DHA contents in commercial drugs and the results were highly agreeable with those determined by high-performance liquid chromatography.
AB - Dihydroartemisinin (DHA) is one of the artemisinin derivatives widely used in artemisinin-based combination therapies (ACTs) for malaria treatment. The availability of a point-of-care device for estimation of DHA quantity would allow a quick quality assessment of the DHA-containing drugs. In this study, 9-O-succinylartemisinin was obtained from microbial fermentation of artemisinin, which was hydrogenated to 9-O-succinyldihydroartemisinin as the hapten for DHA. A monoclonal antibody (mAb), designated as 2G11G4, was identified after screening the hybridoma library, which showed 52.3% cross reactivity to artemisinin, but low or no cross reactivity to artesunate, artemether, and several ACTs partner drugs. Based on this mAb, a highly-sensitive, indirect competitive enzyme-linked immunosorbent assay was designed, which showed 50% inhibition concentration of DHA at 1.16 ng/mL, a working range of 0.26–4.87 ng/mL, and limit of detection of 0.18 ng/mL. In addition, a colloidal gold-based lateral flow immunoassay (dipstick) was developed with an indicator range (indicating sensitivity) of 50–100 ng/mL. This dipstick was evaluated for determination of DHA contents in commercial drugs and the results were highly agreeable with those determined by high-performance liquid chromatography.
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U2 - 10.1016/j.jpba.2018.06.051
DO - 10.1016/j.jpba.2018.06.051
M3 - Article
C2 - 29980021
AN - SCOPUS:85049343921
SN - 0731-7085
VL - 159
SP - 66
EP - 72
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
ER -