Determination of isavuconazole concentration in human plasma by high-performance liquid chromatogra-phy and its clinical application
OBJECTIVE To develop a method of high-performance liquid chromatography(HPLC)for determining the con-centration of isavuconazole in human plasma and to provide a scientific basis for rational dosing of isavuconazole for clinical treat-ment of invasive mold infection.METHODS Protein was precipitated by acetonitrile on a Thermo HPLC separation system(UltiMate 3000)with a Hypersil ODS2(250 mm×4.6 mm,5 μm).Mobile phase was composed of acetonitrile-ammonium acetate(10 mmol·L-1)(55∶45,V/V)at a flow rate of 1 mL·min-1 and a detection wavelength of 285 nm at 25 ℃.RESULTS The method was developed based upon HPLC.It exhibited high specificity and decent linearity(r=0.999 9)within a range of 0.20-20.00 μg·mL-1.Recovery ranged from 94.09％to 102.36％,intra/inter-day RSDs of＜5％,decent stability at room temperature,4 ℃ and-20 ℃ respectively for different time periods.One patient on isavuconazole therapy showed a better thera-peutic effect after plasma concentration was adjusted from 0.79 to 1.89 μg·mL-1.CONCLUSION A rapid,stable and efficient HPLC method for determining drug concentration of isavuconazole in human plasma has been successfully established.Based upon the results of therapeutic drug monitoring(TDM),isavuconazole dosing protocol may be adjusted.It contributes to the safety,efficacy and rationalization of its clinical use.
isavuconazoleplasma concentrationhigh-performance liquid chromatographytherapeutic drug monitoringpharmacovigilance
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