Oluwatobi Oladayo Olakojo^{1, 2, 3} , Eric Beitz², Marc Scherwing², Aremu Olajire Adegoke¹, Sunday Olakunle Idowu¹

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria; ²Pharmazeutisches Institut der Christian-Albrechts-Universität, 24118 Kiel, Germany; ³Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Federal University Oye-Ekiti, Ekiti, Nigeria.

For correspondence:-  Oluwatobi Olakojo   Email: oluwatobi.olakojo@fuoye.edu.ng   Tel:+2348059774566

Received: 4 March 2025        Accepted: 22 August 2025        Published: 31 August 2025

Citation: Olakojo OO, Beitz E, Scherwing M, Adegoke AO, Idowu SO. Colorimetric determination of artemisinin derivatives using 4-nitro-1-naphthalene diazonium tosylate as a coupling reagent. Trop J Pharm Res 2025; 24(8):1015-1026 doi: https://dx.doi.org/10.4314/tjpr.v24i8.6

© 2025 The authors.
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Abstract

Purpose: To present a cost-effective colorimetric method for quantifying artemisinin derivatives, and addressing detection limitations due to their weak chromophoric properties. Methods: The method utilizes 4-nitro-1-naphthalenyldiazonium tosylate as coupling reagent, which reacts with acid-decomposed artemisinin derivatives, forming colored azo adducts, which were optimized for analytical wavelength and detector response. Optimal reaction conditions, like temperature and time, were established, with stoichiometric ratios determined for each analyte. Validation confirmed the method's linearity, precision, accuracy, and limits of detection and quantitation. Results: Artemether, artesunate, and dihydroartemisinin, upon acid decomposition, coupled avidly with diazonium reagent, giving reddish adducts with maximum absorbances at 430, 440, and 430 nm, respectively. Overlaid absorption spectra relative to the reagent and analytes revealed a bathochromic effect. Optimum reaction conditions were established at 50 ?C for 15 - 25 min. Assays were linear over 0 - 16 (artemether), 7.33 - 27.33 (artesunate), 6.08 - 16.21 μg/mL (dihydroartemisinin), with limits of detection of 0.21, 0.073, and 0.068 μg/mL, and overall recovery of 100.9 ± 1.7, 101.9 ± 3.3, and 100.4 ± 3.2 %, respectively. The assay results agreed with International Pharmacopoeia methods. Conclusion: This colorimetric approach offers a reliable and sensitive alternative for artemisinin derivative analysis, enhancing antimalarial quality control where sophisticated equipment is inaccessible.

Keywords: Artemisinin derivatives, Colorimetric analysis, Diazonium coupling reagent, Azo adduct detection, Antimalarial drug quality control

Impact Factor
Thompson Reuters (ISI): 0.6 (2023)
H-5 index (Google Scholar): 49 (2023)