Analytical Methods for Daptomycin Determination: Applications in Biological Matrices and Pharmaceutical Formulations

Daptomycin (DAP) is a cyclic lipopeptide antibiotic indicated for the treatment of serious Gram-positive infections, including complicated skin and soft tissue infections, <i>Staphylococcus aureus</i> bacteremia, and right-sided infective endocarditis. Due to its clinical significance, the reliable quantification of DAP in both biological and pharmaceutical matrices is essential for therapeutic drug monitoring, pharmacokinetic studies, and quality control. This review provides a comprehensive and structured overview of analytical methods developed for DAP determination, based on literature search of Web of Science, PubMed, and ScienceDirect encompassing publications from 2008 to 2025, and including fifty-one studies involving biological matrices - such as plasma, serum, urine, bone, wound fluid, and muscle - and eight studies focused on pharmaceutical formulations. The reviewed methods include liquid chromatography coupled with ultraviolet or mass spectrometric detection, as well as alternative techniques such as spectrofluorimetry, spectrophotometry, voltammetry, and capillary-zone electrophoresis. Sample preparation strategies for analyzing biological matrices, <i>viz.</i> protein precipitation and solid-phase extraction, have also been systematically discussed. By offering a comparative perspective grounded in experimental evidence, this review aims to guide researchers and laboratory professionals in selecting appropriate DAP quantification strategies for both clinical and pharmaceutical applications.