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Molecular Docking Approach and Enantioseparation of Hydroxychloroquine by High-Performance Liquid Chromatography using Amylose Tris (3,5-dimethyl phenyl carbamate) as the Chiral Selector

1Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Jenderal Soedirman, Purwokerto, 53123, Indonesia

2Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia

3Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical and Drug Industries Research Division, National Research Center (NRC) Dokki, Cairo, 12622, Egypt

Received: 6 Jul 2023; Revised: 6 Nov 2023; Accepted: 7 Nov 2023; Published: 15 Nov 2023.
Open Access Copyright 2023 Jurnal Kimia Sains dan Aplikasi under

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The chiral separation of hydroxychloroquine, an antimalarial drug with one chiral center, has been predicted using molecular docking and was proven using the HPLC method. Docking utilized the PM3 semi-empirical method with specific grid coordinates (X = 19.977, Y = 20.069, and Z = 25.901) and a grid size of (X = 20, Y = 20, and Z = 60), employing a grid spacing of 1,000 Å, an exhaustiveness value of 8, and num_modes of 10. The analysis revealed the enhanced stability of R-hydroxychloroquine within the tris amylose complex, resulting in slower retention and elution rates compared to S-hydroxychloroquine. The HPLC experimental validation demonstrates resolution (Rs = 2.23), successfully achieved by employing amylose tris-based chiral columns. The mobile phase composition employed in this study consisted of acetonitrile:aquabidest: dimethylamine (47:52:1, v/v). Detection was performed at 343 nm, and the optimized HPLC method successfully quantitatively determined hydroxychloroquine in a liquid pharmaceutical sample with a percentage recovery of 98.47%.

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Keywords: Chiral separation; Hydroxychloroquine; High-performance liquid chromatography; Molecular docking
Funding: Ministry of Education, Culture, Research and Technology; Universitas Jenderal Soedirman; World Class Research Grants 2023

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