A rapid high-throughput strategy for detecting voriconazole based on surface-enhanced Raman spectroscopy

Area of Science:

• Analytical Chemistry
• Biomedical Engineering
• Pharmacology

Background:

• Voriconazole (VOR) is crucial for invasive aspergillosis but shows high inter-individual pharmacokinetic variability.
• Therapeutic drug monitoring (TDM) is essential for optimizing VOR treatment efficacy and safety.
• Current monitoring methods have limitations, driving the need for novel point-of-care testing (POCT) solutions.

Purpose of the Study:

• To develop and validate a novel Surface-Enhanced Raman Spectroscopy (SERS) method for rapid, label-free quantification of VOR.
• To establish a point-of-care testing (POCT) strategy for voriconazole therapeutic drug monitoring (TDM).
• To assess the clinical utility of the developed SERS method using patient blood samples.

Main Methods:

• Theoretical Raman spectra of VOR were predicted using density functional theory.
• Gold nanoparticles were used as SERS substrates, optimizing detection conditions including nanoparticle characteristics and aggregating agents.
• A novel SERS method was established by combining ethyl acetate extraction and enrichment techniques for VOR detection.

Main Results:

• A sensitive and specific SERS method for VOR detection was successfully developed.
• Optimization of SERS parameters ensured reliable and reproducible measurements.
• The SERS method demonstrated clinical utility when validated against patient blood samples using enzyme-multiplied immunoassay.

Conclusions:

• A rapid, label-free, high-throughput SERS method was developed for VOR TDM.
• This SERS approach represents a promising novel strategy for POCT of clinical antimicrobial drugs.
• The method requires a small sample volume, making it suitable for routine clinical application.