Development of a method for vancomycin monitoring in interstitial fluid using a novel porous microneedle array patch.

Interstitial fluid (ISF) is a promising alternative matrix for therapeutic drug monitoring; however, practical and quantitative ISF-based therapeutic drug monitoring has not been established. The aim of this study was to develop a method to quantify vancomycin concentrations in dermal ISF using novel porous poly(glycolic acid) (PGA) microneedles and characterize vancomycin pharmacokinetics in rat ISF by applying a sodium-based correction method to address evaporation-related variability in the ISF sampling volume. Porous PGA microneedles fabricated using a non-solvent-induced phase separation process passively absorbed ISF within a short insertion time (e.g., 5 min). Vancomycin extracted from MNs was quantified via LC-MS/MS, showing linearity over 0.5-100 μg/mL (R2 = 0.994), precision of <8%, and accuracy within 92-107%. Following intravenous vancomycin administration (30 mg/kg) to rats, ISF concentrations mirrored those in the plasma at the terminal elimination phase, indicating that ISF may serve as a surrogate for plasma kinetics. Sodium-based correction reduced the variability in ISF vancomycin concentrations and improved their correlation with plasma concentrations (R2 = 0.834) relative to weight-based method results. These findings indicate that ISF sampling using PGA-based porous microneedles, combined with sodium-based volume correction, provides a minimally invasive and quantitatively reliable platform for ISF-based therapeutic drug monitoring.