Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato, Tokyo, 105-8512, Japan.
Department of Pharmacy, Keio University Hospital, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
Sci Rep. 2022 Jul 27;12(1):12847. doi: 10.1038/s41598-022-16928-3.
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.
治疗药物监测用于确定适当的药物剂量，在药理学治疗中至关重要。在这项研究中，我们开发了具有各种阳离子特性的温敏色谱柱，用于有效的治疗药物监测。使用作为色谱固定相的改性硅胶珠上的自由基引发剂，通过自由基聚合制备了温敏阳离子共聚物聚（N-异丙基丙烯酰胺-co-n-丁基甲基丙烯酸酯-co-N，N-二甲基氨基丙基丙烯酰胺）（P（NIPAAm-co-BMA-co-DMAPAAm））-改性硅胶珠。所制备的硅胶珠的特性表明，具有各种阳离子特性的温敏聚合物成功地修饰了珠子。在各种温度下，在制备的珠填充柱中几种甾体的洗脱行为表明最佳柱操作温度为 30°C。通过改变柱的阳离子性质和流动相的 pH 值，研究了 13 种药物的适当测量条件。使用开发的柱和具有合适 pH 值的流动相测定血清样品中的药物浓度。使用全水相流动相开发的色谱柱测定人血清样品中的伏立康唑浓度。我们预计开发的色谱柱可用于治疗药物监测，因为可以使用适合临床环境的全水相流动相测量药物浓度。
