Abstract:Therapeutic drug monitoring is a key technology for effective pharmacological treatment. In the present study, a temperature-responsive chromatography column was developed for safe and simple therapeutic drug monitoring without the use of organic solvents. Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel-modified silica beads were prepared via a condensation reaction and radical polymerization. The temperature-dependent elution behavior of the drugs was observed using a PNIPAAm-modified silica-bead packed column… Show more
“…These results indicate that the three types of copolymers were successfully modified on silica beads through radical polymerization. The absorbance of aminopropyl silica beads increased with increasing wavenumber, which led to a small difference in the peak height between the copolymer-modified silica beads and aminopropyl silica beads compared with that of the previously reported FT-IR analysis of the polymer-modified beads 41 . Figure 2 ( A ) FT-IR spectra and ( B ) SEM images of the prepared beads.…”
Section: Resultsmentioning
confidence: 53%
“…In a previous study, a temperature-responsive chromatography column was investigated for applicability in TDM 41 , 42 . Drug concentrations in a sample can be analyzed using temperature-responsive chromatography with all-aqueous mobile phases 41 , 42 .…”
Section: Introductionmentioning
confidence: 99%
“…In a previous study, a temperature-responsive chromatography column was investigated for applicability in TDM 41 , 42 . Drug concentrations in a sample can be analyzed using temperature-responsive chromatography with all-aqueous mobile phases 41 , 42 . However, several analytes have ionic properties and are not effectively retained on the column through only hydrophobic interactions.…”
Therapeutic drug monitoring, which is used to determine appropriate drug doses, is critical in pharmacological therapy. In this study, we developed thermoresponsive chromatography columns with various cationic properties for effective therapeutic drug monitoring. Thermoresponsive cationic copolymer poly(N-isopropylacrylamide-co–n-butyl methacrylate-co–N,N-dimethylaminopropyl acrylamide) (P(NIPAAm-co-BMA-co-DMAPAAm))-modified silica beads, which were used as the chromatographic stationary phase, were prepared by modifying the radical initiator of the silica beads, followed by radical polymerization. Characterization of the prepared silica beads demonstrated that thermoresponsive polymers with various cationic properties successfully modified the beads. The elution behavior of several steroids in the prepared bead-packed columns at various temperatures indicated that the optimal column operating temperature was 30 °C. Appropriate measurement conditions for 13 drugs were investigated by varying the cationic properties of the columns and the pH of the mobile phase. Drug concentrations in serum samples were determined using the developed columns and mobile phases with a suitable pH. Voriconazole concentrations in human serum samples were determined using the developed columns with all-aqueous mobile phases. We anticipate that the developed chromatography columns can be used for therapeutic drug monitoring because drug concentrations can be measured using all-aqueous mobile phases that are suitable in clinical settings.
“…These results indicate that the three types of copolymers were successfully modified on silica beads through radical polymerization. The absorbance of aminopropyl silica beads increased with increasing wavenumber, which led to a small difference in the peak height between the copolymer-modified silica beads and aminopropyl silica beads compared with that of the previously reported FT-IR analysis of the polymer-modified beads 41 . Figure 2 ( A ) FT-IR spectra and ( B ) SEM images of the prepared beads.…”
Section: Resultsmentioning
confidence: 53%
“…In a previous study, a temperature-responsive chromatography column was investigated for applicability in TDM 41 , 42 . Drug concentrations in a sample can be analyzed using temperature-responsive chromatography with all-aqueous mobile phases 41 , 42 .…”
Section: Introductionmentioning
confidence: 99%
“…In a previous study, a temperature-responsive chromatography column was investigated for applicability in TDM 41 , 42 . Drug concentrations in a sample can be analyzed using temperature-responsive chromatography with all-aqueous mobile phases 41 , 42 . However, several analytes have ionic properties and are not effectively retained on the column through only hydrophobic interactions.…”
Therapeutic drug monitoring, which is used to determine appropriate drug doses, is critical in pharmacological therapy. In this study, we developed thermoresponsive chromatography columns with various cationic properties for effective therapeutic drug monitoring. Thermoresponsive cationic copolymer poly(N-isopropylacrylamide-co–n-butyl methacrylate-co–N,N-dimethylaminopropyl acrylamide) (P(NIPAAm-co-BMA-co-DMAPAAm))-modified silica beads, which were used as the chromatographic stationary phase, were prepared by modifying the radical initiator of the silica beads, followed by radical polymerization. Characterization of the prepared silica beads demonstrated that thermoresponsive polymers with various cationic properties successfully modified the beads. The elution behavior of several steroids in the prepared bead-packed columns at various temperatures indicated that the optimal column operating temperature was 30 °C. Appropriate measurement conditions for 13 drugs were investigated by varying the cationic properties of the columns and the pH of the mobile phase. Drug concentrations in serum samples were determined using the developed columns and mobile phases with a suitable pH. Voriconazole concentrations in human serum samples were determined using the developed columns with all-aqueous mobile phases. We anticipate that the developed chromatography columns can be used for therapeutic drug monitoring because drug concentrations can be measured using all-aqueous mobile phases that are suitable in clinical settings.
“…A mixed-mode column was prepared by combining PNIPAAm and PAPTAC beads and packing them into an empty column (4.6 inner diameter × 50 mm length) 44 . Solely PNIPAAm-modified beads packed column and PNIPAAm-modified beads (0.8 g) were suspended in 20 mL of a 1:1:1 mixed solvent of water:methanol:2-propanol.…”
Section: Methodsmentioning
confidence: 99%
“…In the case of the PNIPAAm:PAPTAC = 20:1 column, PNIPAAm-modified beads (0.764 g) and PAPTAC-modified beads (0.0382 g) were suspended in the mixed solvent, while in that of PNIPAAm:PAPTAC = 10:1 column, PNIPAAm-modified beads (0.727 g) and PAPTAC-modified beads (0.0727 g) were suspended in the mixed solvent. The bead suspension was poured into the reservoir of the column packer that was connected to an empty column 44 . Beads were packed to enable a continuous flow of a mixed solvent with a continuous pressure of 350 kg/cm 2 for 1 h 43 .…”
In this study, mixed-mode chromatography columns have been investigated using multiple analyte interactions. A mixed-mode chromatography column was developed using poly(N-isopropylacrylamide) (PNIPAAm) brush-modified silica beads and poly(3-acrylamidopropyl trimethylammonium chloride) (PAPTAC) brush-modified silica beads. PNIPAAm brush-modified silica beads and PAPTAC brush-modified silica beads were prepared by atom transfer radical polymerization. The beads were then packed into a stainless-steel column in arbitrary compositions. The elution studies evaluated the column performance on hydrophobic, electrostatic, and therapeutic drug samples using steroids, adenosine nucleotide, and antiepileptic drugs as analytes, respectively. Steroids exhibited an increased retention time when the column temperature was increased. The retention of adenosine nucleotides increased with the increasing composition of the PAPTAC-modified beads in the column. The antiepileptic drugs were separated using the prepared mixed-mode columns. An effective separation of antiepileptic drugs was observed on a 10:1 PNIPAAm:PAPTAC column because the balance between the hydrophobic and electrostatic interactions with antiepileptic drugs was optimized for the bead composition. Oligonucleotides were also separated using mixed-mode columns through multiple hydrophobic and electrostatic interactions. These results demonstrate that the developed mixed-mode column can modulate multiple hydrophobic and electrostatic interactions by changing the column temperature and composition of the packed PNIPAAm and PAPTAC beads.
Temperature is a widely incorporated stimulus in pharmaceutical applications because of its efficiency as a therapeutic medium; thus, substantial evidence on temperature‐responsive polymer applications is reported. Poly(N‐isopropylacrylamide) (PNIPAAm) is a well‐established, temperature‐responsive polymer that exhibits a low critical solution temperature (LCST) at ≈ 32°C, which is close to physiological temperature. Hence, they are widely used in various pharmaceutical applications, such as drug delivery with nanocarriers and thermogels. Varying the LCST for different applications can be achieved by copolymerization with other hydrophobic or hydrophilic molecules, making it a favorable smart polymer. PNIPAAm is reported to enhance drug delivery by incorporation with nanocarriers and to facilitate prolonged drug delivery, thereby avoiding the burst release of drugs in temperature‐responsive hydrogels. The application of PNIPAAm is not limited to drug delivery, and it is also applied in biomedical applications such as chromatography systems and cell culture applications, where its incorporation in cell culture media enhances cell production. The unique and versatile properties of PNIPAAm render it a promising smart polymer for various functional applications. Hence, this review focuses on the diverse applications of PNIPAAm.This article is protected by copyright. All rights reserved
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