Simple and validated UHPLC method coupled to UV detection for determination of daptomycin in human plasma and urine

Daptomycin, a lipopeptide antibiotic with excellent activity against Gram-positive bacteria, is excreted primarily by the kidneys. Development of effective chromatographic methodologies for the determination of daptomycin in human specimens is necessary for clinical use. This study developed a simple and validated ultra-high-performance liquid chromatography method coupled to ultraviolet detection for determination of daptomycin in human plasma and urine. After the pretreatments involving protein precipitation, the supernatants were separated using a 2.3 µm particle size octadecylsilyl column, and the run time was 1 min. The calibration curves were linear over the concentration ranges of 2-200 mg/L for plasma and 25-300 mg/L for urine. Intra- and inter-assay precision and accuracy values of plasma were within 13.5 and 92-100% and within 10.7 and 100-107%, respectively. Those of urine were within 5.0 and 101-104% and within 3.7 and 100-101%, respectively. The validated method was applied to the determination of plasma and urine samples in patients receiving 4-6 mg/kg of intravenous daptomycin, resulting in sufficient sensitivity for evaluating the plasma exposure and urinary excretion. In conclusion, the present method with acceptable analytical performance can be helpful for evaluating the pharmacokinetic disposition of daptomycin in clinical settings.