Therapeutic Drug Monitoring Using Two-Dimensional Chromatography System Composed of Two Types of Temperature-Responsive Chromatography Columns

Abstract

Therapeutic drug monitoring (TDM) is crucial for enhancing the effectiveness of pharmacological treatments. This study developed two types of two-dimensional (2D) chromatography systems. The primary column used a poly(N-isopropylacrylamide) (PNIPAAm) hydrogel-modified bead-packed column, while the secondary column employed either an octadecyl silyl (ODS) column or a PNIPAAm-terminally-modified column. The primary PNIPAAm-hydrogel-modified column effectively separated serum proteins and drugs, while the secondary ODS column exhibited a sharp peak owing to the drug concentration at the front of the column when an aqueous mobile phase was used. However, drug elution was slow, and the mobile phase required an organic solvent. By contrast, the column packed with PNIPAAm-terminally-modified beads reduced the analysis time, and organic solvent was unnecessary. These findings indicate that the developed two-column 2D chromatography system is advantageous for TDM. This system allows for the analysis of serum-drug samples without the need for sample preparation methods, such as deproteination. Moreover, drug concentration can be determined in a short analysis timeframe without organic solvents in the mobile phase.