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

Voriconazole (VOR) is a first-line drug for the treatment of invasive aspergillosis, while its pharmacokinetic parameters exhibit significant individual variability, necessitating therapeutic drug monitoring (TDM) to ensure optimal outcomes. Given the limitations of current monitoring techniques, it is imperative to develop new point-of-care testing (POCT) methods for detecting antimicrobial drugs. Surface-enhanced Raman spectroscopy (SERS) has shown considerable potential in the field of blood antimicrobial concentration monitoring. In this study, the theoretical Raman spectra of VOR were firstly predicted using dispersion-corrected density functional theory with the B3LYP/6-311++G(d,p) basis set. Subsequently, using gold nanoparticles as the SERS substrate and a 96-well plate padded with Al foil at the bottom as the measuring carrier, the detection conditions were optimized regarding the particle size and state of the gold nanoparticles, the type, concentration, and amount of the aggregating agents, as well as the volume of the VOR solution added. Finally, a novel SERS method for determining VOR concentration was established by combining ethyl acetate extraction and enrichment techniques. The clinical utility of the SERS method was verified using 18 patient blood samples, with an enzyme-multiplied immunoassay technique serving as the control. This preliminary study developed a rapid, label-free, high-throughput, and small sample size method for TDM of VOR, representing a potential novel strategy for POCT of clinical antimicrobial drugs.