CHEMICAL DERIVATIZATION OF ZIDOVUDINE BASED ON CLICK REACTION FOR NOVEL ANALYTICAL METHOD DEVELOPMENT
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Date
2023-03-19
Authors
Kyan Bransi
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Abstract
ABSTRACT
Zidovudine is a drug used for the treatment of patients that are infected with the human immunodeficiency virus. It inhibits HIV-reverse transcriptase. Zidovudine has significant dose-limiting toxicities drug-specific, resulting in a small therapeutic window between the minimum and the maximum effective and tolerated doses, respectively. Serious adverse effects among them include hepatic abnormalities, myopathy, and bone marrow toxicity. Hence, a demand exists for analytical technologies that enable efficient and accurate measurements of Zidovudine. The adapted analytical techniques must have sufficient sensitivity, selectivity, or both in order to have more manageable and accurate measurements of various chemical procedures. Converting functional groups within a molecule is one of the adaptive techniques used in chemical derivatization. In this study, the development of a new analytical method for the chemical derivatization of Zidovudine was proposed. To that end, a click reaction with azide-conjugated alkyne was employed, resulting in a five-membered heterocycle (1,2,3-triazole) and an extended conjugation. The aim is to develop a sensitive and selective analytical method. The proposed analytical method has been developed using HPLC with UV/Vis detector and validated according to the International Conference of Harmonization and the Food and Drug Administration guidelines and with the use of the parameters such as accuracy, linearity, range, precision, limit of detection, and limit of quantitation. The developed method adapted max=260 nm for the measurement of the derivatized Zidovudine. The method used HPLC using mobile phase Water-ACN 70:30 v/v. The eluted peak of the derivatized Zidovudine was separated from other used derivatization reagents. The analytical method was then validated, and validation parameters were found to be within the accepted limits. The developed method was found to be linear (R2 = 0.994), precise (RSD = 0.59), and accurate (% recovery = 101.17). Moreover, the developed method was sensitive to LOD (4*10-8 mg/ml) and LOQ (4*10-7 mg/ml). Therefore, the developed method is simple and feasible with high sensitivity and selectivity. Zidovudine may be analyzed in a variety of dosage forms and raw materials, including active pharmaceutical components. This line of research may be pursued further in the future, and the technique that has been established may be adopted in the testing of Zidovudine in biological systems.
Keywords: Zidovudine; Click Reaction; HPLC; Derivatization.