Therapeutic Drug Monitoring Using a Poly(N-isopropylacrylamide) Hydrogel-Modified Bead-Packed Column with an All-Aqueous Mobile Phase without Sample Deproteinization

Abstract

Therapeutic drug monitoring (TDM) is vital for effective optimization of pharmacological treatments. In this study, we engineered a chromatography column that is sensitive to temperature fluctuations, thereby enabling safe and straightforward TDM without relying on organic solvents. Silica beads were modified by applying poly(N-isopropylacrylamide) (PNIPAAm) hydrogels, using a condensation reaction to modify the initiator, followed by radical polymerization to integrate the PNIPAAm hydrogel. We investigated the elution behavior of the drugs at varying temperatures using a PNIPAAm-modified silica bead-packed column and an aqueous mobile phase. Model samples composed of drugs and serum proteins were used to assess the elution behavior within the column. At a column temperature of 30°C, the serum proteins and drugs were successfully separated. The drug concentrations in the samples were quantified by constructing a calibration curve. Experimental results indicate that the chromatography column has significant benefits for TDM, as it allows the determination of drug concentrations in serum without requiring organic solvents in the mobile phase or sample preparation steps.