Rapid Therapeutic Drug Monitoring of Voriconazole Based on High-Performance Liquid Chromatography: A Single-Center Pilot Study in Outpatients

<b>Background/Objectives:</b> Voriconazole (VRCZ) use requires accurate monitoring to avoid suboptimal drug levels and adverse effects. In addition, the appearance of resistant fungal strains is a problem that needs attention. Blood concentration measurement is the monitoring technique of choice; however, it is slow, limiting its clinical application. This study aimed to evaluate the clinical utility of rapid therapeutic drug monitoring (TDM) for VRCZ using high-performance liquid chromatography with ultraviolet detection (HPLC-UV) compared to conventional outsourced liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing in outpatient care. <b>Methods</b>: VRCZ blood concentrations were measured using HPLC-UV and LC-MS/MS. Reporting times, accuracy, and clinical outcomes were assessed for outpatients receiving VRCZ treatment. Safety was monitored for renal, hepatic, and visual toxicities. <b>Results</b>: HPLC-UV significantly reduced reporting times (0.433 h vs. 74.3 h, <i>p</i> < 0.001), and Deming's regression analyses showed a strong correlation with LC-MS/MS results (Pearson's r = 0.988). Bland-Altman analysis showed an average difference of 0.025 μg/mL between HPLC-UV and LC-MS/MS. Prospective monitoring of three outpatients revealed no adverse events, enabling safe and effective VRCZ dosing. <b>Conclusions</b>: Rapid VRCZ TDM using HPLC-UV is a cost-effective and feasible approach for outpatient care, significantly improving reporting times and patient safety. Further studies and cross-facility collaboration are needed to expand its application.