Development and validation of miniaturized turbidimetric method for the analysis of daptomycin for injection

Abstract

Daptomycin is a cyclic lipopeptide antimicrobial obtained through the fermentation of Streptomyces roseosporus and whose mechanism of action occurs through the inhibition of membrane potential and subsequent inhibition of protein synthesis and cell death. Reports of bacterial resistance to daptomycin are not common, and this antimicrobial is very active against Gram-positive bacteria, including resistant strains such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. For this reason, it is an extremely important drug for clinical practice nowadays. It is administrated intravenously and its commercialization is made under the tradename CubicinTM in the pharmaceutical dosage form of lyophilized powder for solution for injection. There are few papers in literature that describe analytical methods for daptomycin analysis, and only the minority of them are related to environmentally friendly methods. Miniaturized microbiological methods are not found. Considering the importance of the development and validation of new methods of analysis to guarantee the quality of the drug, this project aims, based on the principles of Green Chemistry, to perform a miniaturized turbidimetric microbiological assay to analyze the potency of daptomycin in lyophilized powder. This method is interesting, since it is carried out in microplates and makes use of low volumes of culture medium, water and other materials. In addition, it does not use organic solvents for its analysis, which also contributes to the environmentally favorable aspect of the method. It is an innovative, practical and green method that can be used in routine Quality Control analyzes of this drug.