Abstract: AIM: To establish an ultra high performance liquid chromatography (UPLC) method for the determination of micafungin in plasma of critically ill patients. And to establish a model for estimating the area under the concentration-time curve (AUC) of micafungin by limited sampling strategy.  METHODS: Patients with severe infection were administrated with micafungin once a day, 1 h for each infusion. The blood samples were collected before administration and 1, 2, 4, 8, 12, 24 h after administration and were measured by UPLC.The pharmacokinetic parameters were calculated by Phoenix winnonlin 6.4, and the drug concentrations at 2-4 blood collection points were analyzed with SPSS 22.0 to establish limited sampling models. RESULTS: The calibration curve was linear over a concentration range of 1.0 to 50 μg/mL (r2=0.994) and the lower limit of quantification was 1.0 mg/L.The recovery rate was 73.20%, and the precision relative standard deviation (RSD) were both lower than 15%. AUC was estimated by blood drug concentration at 2-4 time points, of which C4, C12 at 2 time points, C4, C12, C24 at 3 time points, C4, C8, C12, C24 at 4 time points had good prediction performance, and r2 was 0.986, 0.995, 0.996 respectively. Combining the prediction accuracy and operability, the recommended 3 time-point scheme equation was 4.578+7.263×C4+9.684×C12+6.411×C24.CONCLUSION: The method is simple and quick, with high specificity and sensitivity, therefore it is suitable for the detection of micafungin in the human plasma. The AUC0-24 can be accurately estimated by the concentration of micafungin at 4, 12, 24 h after administration, which can be applicable to the guidance for individualized micafungin use in clinical practice.

Key words: micafungin, ultra high performance liquid chromatography, therapeutic drug monitoring, limited sampling strategy