Chemical-pharmaceutical analysis and stability studies of daptomycin injectable preparations

Abstract

The emergence of microorganisms resistant to a large number of clinically approved antimicrobial agents has emerged as a crisis of global proportions and it has limited the options for the treatment of bacterial infections. As a strategy for combating these microorganisms, the development of drugs with novel mechanisms of action is in evidence. In this context, a new class of antimicrobials stands out, the cyclic lipopeptides, which has the daptomycin as the first member approved. The daptomycin´s mechanism of action is unique and it is based on the drug insertion in the bacterial cytoplasmic membrane, with the aid of calcium ions, with subsequent leakage of intracellular ions, resulting in depolarization, loss of membrane potential and rapid bactericidal effect. Daptomycin is distributed commercially as CubicinTM and presents selective action against Gram-positive bacteria, including strains resistant to methicillin and vancomycin. It is indicated for the treatment of complicated skin and soft tissues infections as well as bloodstream infections caused by Staphylococcus aureus. There are few studies in the literature regarding the development of analytical methodologies for this cyclic lipopeptide. In this way, researches involving the development of analytical methods are essential and highly relevant to optimize the analysis of this drug in the industry and ensure the quality of the commercialized product. The aim of this innovative project is to develop and validate analytical methods for analysis of daptomycin in pharmaceutical formulation using spectrophotometry in the ultraviolet and infrared regions, capillary electrophoresis, high performance liquid chromatography and microbiological assay, as well as conducting stability studies, which one will have a part held in sandwich PhD at the University of South Australia (Adelaide, SA, Australia). (AU)