High-Speed Analysis of Voriconazole in Plasma Using Triple Quadrupole LC/MS/MS (LCMS-8050)

Significance of the topic

Voriconazole is a key antifungal agent requiring precise plasma quantification to guide dosing and ensure therapeutic efficacy. High-speed analysis enhances throughput in clinical and research laboratories.

Aims and overview of the study

This work demonstrates a fast and straightforward method to quantify voriconazole in human plasma using a triple quadrupole LC/MS/MS system. The study establishes calibration, validates accuracy and precision, and highlights rapid sample processing.

Methodology and sample preparation

A simple deproteinization protocol was applied:

• Mix 50 µL plasma with 50 µL internal standard (voriconazole-d3, 1 µg/mL) and 150 µL acetonitrile
• Vortex and centrifuge at 14 000 rpm, 4 °C, 5 min
• Inject 1 µL supernatant for analysis

Used instrumentation

The analysis employed a Shimadzu LCMS-8050 triple quadrupole mass spectrometer with:

• Shim-pack GIS column (75×2.1 mm, 3 µm)
• Mobile phase A: 10 mmol/L ammonium acetate in water; B: methanol
• Gradient from 30 to 100% B over 1.5 min, total run time 5 min
• ESI in positive ion mode, MRM transitions 350.20→281.20 for voriconazole and 353.20→284.20 for voriconazole-d3

Main results and discussion

Calibration was linear from 0.1 to 10 µg/mL (r ≥ 0.999). Standard samples showed repeatability ≤5% and accuracy within 100 ±10%. QC samples (0.2, 4, 8 µg/mL) achieved repeatability ≤2% and accuracy between 95 and 105%. Chromatographic separation was complete within 2.5 min per run.

Benefits and practical applications

The method offers:

• Rapid turnaround with minimal sample preparation
• Cost-effective deproteinization without solid phase extraction
• High sensitivity and reproducibility suitable for therapeutic drug monitoring

Future trends and applications

Advances may include multiplexed antifungal panels, microflow LC to reduce solvent use, and integration with automated sample handling for higher throughput. Isotope-labeled standards will support other drug analyses.

Conclusion

This high-speed LC/MS/MS method provides reliable quantification of voriconazole in plasma with excellent linearity, precision, and accuracy, facilitating clinical and pharmacokinetic studies.

Reference

• Pharmaceutical Sciences Department, Tohoku University Hospital (cooperative contribution)