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Pharmacokinetics and Tissue Distribution of Alnustone in Rats after Intravenous Administration by Liquid Chromatography-Mass Spectrometry

甲酸 药代动力学 色谱法 化学 最大值 液相色谱-质谱法 分布(数学) 组织分布 药理学 体内 串联质谱法 校准曲线 咖啡因 质谱法 高效液相色谱法 代谢物 选择性反应监测 口服 生物利用度 医学 分配量 蛋白质沉淀 检出限 内科学 生物 生物技术
作者
Yang Song,Yu Zhou,Xiaoting Yan,Jing-Bo Bi,Xin Qiu,B. X. Yu,Kefei Wang,Yuan Zhang,Xuesong Feng
出处
期刊:Molecules [Multidisciplinary Digital Publishing Institute]
卷期号:24 (17): 3183-3183 被引量:5
标识
DOI:10.3390/molecules24173183
摘要

Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m/z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision (RSD) ranged from 1.1–9.0 % to 3.3–8.6%, respectively and the intra- and inter-day assay accuracy (RE) was between −8.2–9.7% and −10.3–9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (Cmax) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC0–t) value was 6009.79 ± 567.30 ng/mL∙h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.
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