Title:Potential Impurities of Tigecycline: Synthesis, Isolation, Characterization and In Vitro Pharmacological Evaluation
Volume: 16
Issue: 6
Author(s): Selliamman Palaniyandi Nallusamy Sharavanan, Chidambaram Subramanian Venkatesan, Singaram Sathiyanarayanan and Senthamaraikannan Kabilan*
Affiliation:
- Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu 608002,India
Keywords:
Tigecycline, potential impurities, NMR, in vitro antimicrobial, antioxidant activity, ICH.
Abstract:
Background: Tigecycline is a known antibiotic in the tetracycline family and a chemical
analog of minocycline. It may be used for the treatment against drug-resistant bacteria.
Methods: 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 the toxicological data. The antimicrobial activity
revealed that the impurity 4 shows excellent activity towards both Gram-positive and Gram-negative
bacteria when compared with 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 with tigecycline. There was no activity observed on fungi for both
isolated degradants as well as tigecycline.
