Validation and clinical evaluation of an ultra-performance liquid chromatography with ultraviolet detector (UPLC-UV) method for plasma quantification of micafungin.

Factors associated with interindividual variability in the pharmacokinetics of micafungin have been identified. This variability can cause underexposure and loss of drug efficacy. For this reason, a simple, fast, cost-effective and sensitive ultra-performance liquid chromatography ultraviolet detector (UPLC-UV) method was developed and validated for the quantification of micafungin. The method involves simple plasma precipitation by UPLC with a reversed phase C18 column at 40ºC coupled with ultraviolet detection set at a wavelength of 264 nm. The mobile phase consisted of a mixture 42/58 of potassium phosphate 20mM and acetonitrile. The method was validated over the concentration range of 0.25-15.0 mg/L and proved to be reliable and reproducible with an average percentage of recoveries of 101.59 ± 3.93% and inter- and intra-day variation coefficients lower than 15% in all cases. The method was successfully applied in determining 30 samples from 10 patients being treated with micafungin. Thus, the method proposed could be useful to facilitate the implementation of therapeutic drug monitoring (TDM) for personalizing micafungin treatment in invasive fungal infections.