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Development of single- and multiplex immunoassays for rapid detection and quantitation of amodiaquine in ACT drugs and rat serum

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Abstract

Amodiaquine (AQ) is a commonly used antimalarial drug, and N-desethyl-AQ (N-DEAQ) is an active metabolite of AQ. Given the significance of drug quality in the management of malaria cases, this study aims to develop antibody-based assays for the detection and quantitation of AQ without the need for sophisticated equipment. Two monoclonal antibodies (mAbs) against AQ, designated as JUN7 and TE7, were selected, which showed 72.7% and 9.5% cross-reactivity to N-DEAQ, respectively. These mAbs showed <0.1% cross-reactivity to other commonly used antimalarial drugs. An indirect competitive enzyme-linked immunosorbent assay (icELISA) based on JUN7 showed a 50% inhibitory concentration (IC50) of 0.16 ng/mL and a working range of 0.06–0.46 ng/mL. A lateral flow immunoassay (LFIA) based on JUN7 was also developed with a working range of 2.58–30.86 ng/mL. The icELISA and LFIA were applied for the quantification of AQ in commercial drugs, and the results were comparable to those determined using high-performance liquid chromatography. In addition, a combination dipstick for simultaneous, qualitative analysis of AQ and artesunate was developed. All immunoassays based on JUN7 can be applied for quality control of AQ-containing artemisinin-based combination therapies. As TE7 showed low cross-reactivity to N-DEAQ, an icELISA based on TE7 was developed with an IC50 of 0.38 ng/mL and a working range of 0.14–1.67 ng/mL. The TE7 icELISA was applied for the study of pharmacokinetics of AQ in rat serum after intragastric administration, and the results were consistent with those of previous studies.

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Acknowledgments

This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (U19AI089672).

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Author notes

  1. Jingqi Qian and Mian Wang contributed equally to this work.

Authors and Affiliations

  1. College of Agriculture and Biotechnology, China Agricultural University, Beijing, 100193, China

    Jingqi Qian, Rui Feng, Jiaqi Zhang, Chencheng Ye, Man Zhang & Baomin Wang

  2. College of Food and Bioengineering, Xihua University, Chengdu, 610039, Sichuan, China

    Mian Wang

  3. College of Biological and Sciences, China Agricultural University, Beijing, 100193, China

    Zhaoxiang Wang

  4. Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, FL, 33612, USA

    Liwang Cui

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  1. Jingqi Qian
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Correspondence to Baomin Wang or Liwang Cui.

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The animal experiments were performed in compliance with the Animal Welfare Act of the U.S. Department of Agriculture. All the animal treatment procedures were approved by the Animal Care Committee of China Agricultural University.

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The authors declare that they have no competing interests.

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Qian, J., Wang, M., Wang, Z. et al. Development of single- and multiplex immunoassays for rapid detection and quantitation of amodiaquine in ACT drugs and rat serum. Anal Bioanal Chem 414, 1631–1640 (2022). https://doi.org/10.1007/s00216-021-03787-6

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  • DOI: https://doi.org/10.1007/s00216-021-03787-6

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