Qiong Lou,Jun Wen,Yuanying Jiang,Jinghua Huang,Guorong Fan,Fenyun Song
A reliable liquid chromatography/tandem mass (LC-MS/MS) method was developed for quantitation of 3′, 4′-dimethoxy flavonol-3-β- d -glucopyranoside (DF3G) in rat plasma using pantoprazole as the internal standard. An Agilent C18 column (100 mm × 3 mm, 3.5 μm) was performed for chromatographic separation with the mobile phase composed of methanol-water (containing formic acid) at a flow rate of 0.4 mL/min. A triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source in positive ion mode was applied to quantitative analysis by multiple reacting monitoring (MRM). The MRM precursor-product ion transition of DF3G and Pantoprazole (IS) were m / z 461.1 → 299.2 and 383.9 → 200.2, respectively. Calibration curves were recovered in a concentration range of 1–500 ng/mL for plasma with a limit of lower quantification (LLOQ) of 1 ng/mL. The intra-day and inter-day precision were not >10%. The accuracy of DF3G ranged from −10% to 0.53% in quality control (QC) samples at three concentrations. DF3G was not degraded during the analysis and the storage period. All the data were validated in accordance with the FDA bioanalytical method validation guideline. The LC-MS/MS method was successfully employed in the pharmacokinetic study of the DF3G after oral administration and intravenous injection in rats.
Lin Tang,Ao Wang,Hecheng Wu,Wenkai Liu,Feng Luo,Jiehua Li,Zhen Li,Hong Tan
Polyurethanes are predominant materials for medical catheter manufacturing owing to their favorable physicochemical properties and biocompatibility. However, the drug-polyurethane interactions compromise therapeutic infusion efficacy and restrict its application in intravenous tubing. There are gaps in systematic research on sorption mechanisms pertaining to polyurethane infusion systems. This study investigates the structure–sorption relationship between polyurethane and active pharmaceutical ingredients (APIs), through combined investigations of dynamic sorption kinetics, static equilibrium sorption, and molecular dynamics simulations. It was revealed that enhanced molecular interactions in highly microphase-mixing polyurethanes reduced the free volume, thereby decreasing drug diffusion rates. The API sorption process exhibits three-stage Fickian diffusion behaviors. Equilibrium drug sorption concentration and equilibrium drug sorption capacity can be calculated from the initial drug concentration. Freundlich constant (Kf) and partition coefficient (K) effectively represent the drug sorption capacity. Molecular dynamics simulations further quantify binding energetics, identifying Lennard–Jones short-range (LJ-SR) interactions as the predominant driver of drug-polymer adhesion. These findings provide insights for optimizing polyurethane formulations to minimize drug sorption and maintain therapeutic efficacy.
Mengyao Mu,Mengmeng Zhang,Jie Liu,Ke Ren,Hui Liu,Lixian Yip,Kai Guo,Feifei Teng,Jian Dong,Xueli Xu,David Tai Leong,Xiao Sun
Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure. Once ineffective, patients may miss the critical window for pursuing alternative treatment options. Herein, a manganese sulfide nanoplatform loaded with proton pump inhibitor (PPI) is developed. This nanoplatform is designed for visualizing tumor acidosis degree by magnetic resonance imaging (MRI), achieving real-time therapeutic efficacy precognition. The nanoplatform releases PPI, H 2 S, and Mn 2+ within the acidic lysosome of tumor cells. PPI inhibits V-ATPase expression, leading to an increase in intracellular H + levels. H 2 S accelerates glucose consumption of tumor cells, producing more lactic acid and further inducing tumor acidosis. Tumor acidosis in turn accelerates the nanoplatform's degradation, achieving higher tumor MRI. As the tumor acidosis degree correlates positively with tumor regression, real-time visualization of acidosis degree effectively predicts future therapeutics. Interestingly, tumor acidosis achieves efficient tumor metastasis suppression rather than increases it. Overall, this work presents a nanoplatform capable of visualizing tumor acidosis in real-time and precisely predicting future therapeutics.
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