Objective: To establish the rapid

accurate and high-throughput method for the determination of voriconazole (VRC) concentration in human serum by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)

and to clarify the necessity of drug concentration monitoring for VRC in different age groups. Methods: VRC isotope (VRC-d3) was set as the internal standard

UPLC-MS/MS method was established to detect the concentration of VRC in human serum. The accuracy of the method was verified by College of American Pathologists (CAP) external quality assessment. The clinical application results were retrospectively analyzed to discuss the importance of drug concentration monitoring of VRC in different age groups. Results: The LC-MS/MS running time was 1.5 min and showed good linearity (R>0.999) in the mass concentration range from 0.2 to 80.0 μg/mL with respect to the peak area ratio of the analyte to the internal standard. The accuracy ranged from 103.5% to 107.3%

and the intra-day and inter-day precision relative standard deviation (RSD) were <10%. The extraction recoveries of VRC were from 95.20% to 98.27% with RSD<10%. The extraction recoveries of VRC-d3 were from 97.12% to 99.73% with RSD<10%. The deviation of CAP results from the mean value ranged from -7.74%~-0.85%. Nearly 50% of the clinical samples tested were out of the therapeutic range

with large individual differences

especially in pediatric patients. Conclusion: The UPLC-MS/MS method established in this study is sensitive and accurate

simple and rapid

and greatly shortens the reporting period

which is suitable for the rapid detection of VRC blood concentration in children and adults. Individual differences in VRC blood concentration in patients of different age groups are large

and VRC blood concentration monitoring is urgently needed

especially in younger children from 0 to 2 years