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一种用于大鼠血浆中戈米辛 D 定量的快速 UPLC-MS 方法及其在药代动力学和生物利用度研究中的应用。

A Rapid UPLC-MS Method for Quantification of Gomisin D in Rat Plasma and Its Application to a Pharmacokinetic and Bioavailability Study.

机构信息

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.

出版信息

Molecules. 2019 Apr 10;24(7):1403. doi: 10.3390/molecules24071403.

Abstract

Gomisin D, a lignan compound isolated from , is a potential antidiabetic and anti-Alzheimer's agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry method (UPLC-MS/MS) was developed and validated to quantify gomisin D in rat plasma for a pharmacokinetic and bioavailability study. Acetonitrile was used to precipitate plasma proteins. Separations were performed on a BEH C18 column with a gradient mobile phase comprising of acetonitrile and water (0.1% formic acid). An electrospray ionization source was applied and operated in the positive ion mode. The multiple reaction monitoring mode (MRM) was utilized to quantify gomisin D and nomilin (internal standard, IS) using the transitions of / 531.2 → 383.1 and / 515.3 → 161.0, respectively. The calibration curve was linear over the working range from 1 to 4000 ng/mL ( = 0.993). The intra- and interday precision ranged from 1.9% to 12.9%. The extraction recovery of gomisin D was in the range of 79.2-86.3%. The validated UPLC-MS/MS method was then used to obtain the pharmacokinetic characteristics of gomisin D after intravenous (5 mg/kg) and intragastric (50 mg/kg) administration to rats. The bioavailability of gomisin D was 107.6%, indicating that this compound may become a promising intragastrical medication. Our results provided useful information for further preclinical studies on gomisin D.

摘要

五味子甲素 D,一种从五味子中分离得到的木脂素化合物,是一种有潜力的抗糖尿病和抗老年痴呆症药物。最近,五味子甲素 D 被用作一些中药配方的质量标志物。在这项研究中,建立并验证了一种快速超高效液相色谱/串联质谱法(UPLC-MS/MS),用于定量大鼠血浆中的五味子甲素 D,以进行药代动力学和生物利用度研究。用乙腈沉淀血浆蛋白。采用 BEH C18 柱进行分离,以包含乙腈和水(0.1%甲酸)的梯度流动相进行洗脱。采用电喷雾电离源,在正离子模式下进行操作。采用多重反应监测模式(MRM),使用 / 531.2→383.1 和 / 515.3→161.0 的转换,分别定量五味子甲素 D 和诺米林(内标,IS)。校准曲线在 1 至 4000ng/mL(r=0.993)的工作范围内呈线性。日内和日间精密度的范围为 1.9%至 12.9%。五味子甲素 D 的提取回收率在 79.2-86.3%范围内。所建立的 UPLC-MS/MS 方法随后用于测定大鼠静脉(5mg/kg)和灌胃(50mg/kg)给药后五味子甲素 D 的药代动力学特征。五味子甲素 D 的生物利用度为 107.6%,表明该化合物可能成为一种有前途的口服药物。我们的研究结果为进一步研究五味子甲素 D 提供了有用的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eed1/6479676/08604e6ba203/molecules-24-01403-g001.jpg

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