Rapid Assay for the Therapeutic Drug Monitoring of Edoxaban

Abstract

Edoxaban is a direct oral anticoagulant (DOAC) that has been recently indicated for the treatment of pulmonary embolism (PE) in SARS-CoV-2 infections. Due to its pharmacokinetic variability and a narrow therapeutic index, the safe administration of the drug requires its therapeutic drug monitoring (TDM) in patients receiving the treatment. In this work, we present a label-free method for the TDM of edoxaban by surface enhanced Raman spectroscopy (SERS). The new method utilises the thiol chemistry of the drug to chemisorb its molecules onto a highly sensitive SERS substrate. This leads to the formation of efficient hotspots and a strong signal enhancement of the drug Raman bands, thus negating the need for a Raman reporter for its SERS quantification. The standard samples were run with a concentration range of 1.4 × 10−4 M to 10−12 M using a mobile phase comprising of methanol/acetonitrile (85:15 v/v) at 291 nm followed by the good linearity of R2 = 0.997. The lowest limit of quantification (LOQ) by the SERS method was experimentally determined to be 10−12 M, whereas LOQ for HPLC-UV was 4.5 × 10−7 M, respectively. The new method was used directly and in a simple HPLC-SERS assembly to detect the drug in aqueous solutions and in spiked human blood plasma down to 1 pM. Therefore, the SERS method has strong potential for the rapid screening of the drug at pathology labs and points of care.

A strategy for low-cost portable monitoring of plasma drug concentrations using a sustainable boron-doped-diamond chip

“…The surface plasmon resonance sensor employing a DNA aptamer can measure the concentration of an antineoplastic drug, irinotecan, with a high selectivity in a range of 0.2–12.8 μM [ 6 ]. More excellent sensitivity is described in a surface-enhanced Raman spectroscopy method with a direct anticoagulant, edoxaban, (limit of quantification: 1 pM) [ 7 ]. An electrode based on CeBiO x nanofiber detects acetaminophen with a low detection limit of 0.2 μM [ 8 ].…”