Clinical feasibility of a label-free SERS assay for therapeutic drug monitoring of methotrexate

We present a therapeutic drug monitoring (TDM) feasibility study using a label-free surface-enhanced Raman spectroscopy (SERS)-based assay for quantifying methotrexate (MTX) from samples collected from children with acute lymphoblastic leukemia undergoing high-dose MTX therapy. We show that, when combined with an appropriate sample preparation (solid phase extraction) and multivariate data analysis (partial least squares regression), the SERS assay demonstrated a good correlation with a reference chromatographic method (r = 0.889, p < 0.005). We also found that the SERS-based approach underestimated MTX concentration, with a 10% bias calculated, but both methods showed similar variability (RSD of 8.4% for HPLC and 11.6% for SERS). The presented results are strong evidence that SERS can be used for TDM of MTX, and this work brings us one step closer to implementing a SERS-based assay in clinics.