Simultaneous determination of four antibiotics in human plasma by high-performance LC–MS/MS: application to therapeutic drug monitoring

Background: Aimed to simultaneously measure linezolid, voriconazole, cefoperazone and fluconazole in human plasma suitable for therapeutic drug monitoring applications, a robust, rapid and easy-to-use HPLC–MS/MS approach was developed and validated. Materials & methods: Protein precipitation was used to prepare analytes from 100 μl plasma. HPLC was employed for analyte separation, and quantification was conducted via multiple-reaction monitoring in positive ion mode. The methodology was fully validated. Results & conclusion: All four antibiotics were found to be stable under the tested conditions, and accuracy values ranged from 90.96 to 113.25% and CV values were <14.0%. This HPLC–MS/MS method can be used for routine clinical therapeutic drug monitoring of linezolid, voriconazole, cefoperazone and fluconazole simultaneously.