This paper reports the validation of an assay for obtusifolin based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) and its application to a preclinical pharmacokinetic study in rats. After sample preparation of plasma and tissue homogenates by protein precipitation, the analyte and internal standard (IS) were separated by a reversed‐phase chromatographic system in a run time of 5.0 min and detected by negative ion electrospray ionization followed by selected reaction monitoring of the precursor‐to‐product ion transitions at m/z 283.0–268.1 for obtusifolin and m/z 329.0–314.1 for IS. The assay was linear in the concentration range 1.0–500 ng/ml with the LLOQ of 1.0 ng/ml. In the pharmacokinetic study of an intragastric administration of 1.3 mg/kg obtusifolin, the maximum plasma concentration of obtusifolin was 152.5 ± 62.3 ng/ml, reached at 0.39 ± 0.17 h. The AUC_0–t and AUC_0–∞ were 491.8 ± 256.7 and 501.7 ± 256.7 ng × h/ml, respectively, with an elimination half‐life of 3.1 ± 0.7 h. Obtusifolin was rapidly distributed into tissues, with the highest distribution in the liver and less in the brain. These results will give some insights for further pharmacological investigation of obtusifolin.

中文翻译：

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液相色谱-串联质谱法研究奥布斯替林在大鼠体内的药代动力学和组织分布

本文报道了一种基于液相色谱-串联质谱法（LC-MS / MS）的奥多斯福林测定方法的验证及其在大鼠临床前药代动力学研究中的应用。在通过蛋白质沉淀制备血浆和组织匀浆的样品后，通过反相色谱系统在5.0分钟的运行时间中分离分析物和内标（IS），并通过负离子电喷雾电离进行检测，然后对反应进行选定的监测奥布斯替林和m / z的前体离子到产品离子的跃迁在m / z 283.0–268.1适用于IS的329.0–314.1。该测定法在浓度范围为1.0–500 ng / ml时呈线性，LLOQ为1.0 ng / ml。在胃内施用1.3 mg / kg奥布斯福林的药代动力学研究中，奥布索夫林的最大血浆浓度为152.5±62.3 ng / ml，达到0.39±0.17 h。所述AUC _0-吨和AUC _0-∞分别为491.8±256.7和501.7±256.7纳克×H /毫升，分别为3.1±0.7 h的消除半衰期。Obtusifolin迅速分布到组织中，在肝脏中分布最高，而在大脑中分布较少。这些结果将为进一步的奥布索夫林药理研究提供一些见识。