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Potential Impurities of Tigecycline: Synthesis, Isolation, Characterization and In Vitro Pharmacological Evaluation

Author(s):

S.P.N. Sharavanan, C.S. Venkatesan, S. Sathiyanarayanan and S. Kabilan*   Pages 1 - 13 ( 13 )

Abstract:


Background: Tigecycline is a known antibiotic in the tetracycline family and a chemical analog of minocycline. It may be used for treatment against drug-resistant bacteria.

Method: HPLC method was used for related substance analysis. The degraded impurities during the process were isolated and characterized by IR, HRMS (High Resolution Mass Spectrometry) and NMR spectral analysis.

Result: Four impurities of tigecycline, a broad spectrum antibacterial agent, were identified, synthesized and characterized. The in vitro biological evaluation of the isolated compounds showed significant antimicrobial and antioxidant properties to that of tigecycline. Apart from these, the tigecycline drug substance showed significant degradation under oxidation conditions.

Conclusion: The extensive investigational data confirm the structure of the four impurities. The specification limit for these impurities is applied based on toxicological data. The antimicrobial activity revealed that the impurity 4 shows excellent activity towards both Gram-positive and Gram-negative bacteria when compared to tigecycline. The results obtained for DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant activity concluded that the impurity 2 and the impurity 3 showed good antioxidant properties when compared to tigecycline. There was no activity observed on fungi for both isolated degradants as well as tigecycline.

Keywords:

Tigecycline, potential impurities, NMR, in vitro antimicrobial, antioxidant activity

Affiliation:

Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu 608002, Gland Pharma Ltd, Research and Development, D.P.Pally, Hyderabad 500 043, Gland Pharma Ltd, Research and Development, D.P.Pally, Hyderabad 500 043, Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu 608002



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