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一种用于定量小鼠血浆中反式-ε-葡萄素的简单灵敏的液相色谱-串联质谱法及其在小鼠药代动力学研究中的应用。

A simple and sensitive liquid chromatography-tandem mass spectrometry method for trans-ε-viniferin quantification in mouse plasma and its application to a pharmacokinetic study in mice.

作者信息

Kim Jiseon, Min Jee Sun, Kim Doyun, Zheng Yu Fen, Mailar Karabasappa, Choi Won Jun, Lee Choongho, Bae Soo Kyung

机构信息

College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea.

College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea.

出版信息

J Pharm Biomed Anal. 2017 Feb 5;134:116-121. doi: 10.1016/j.jpba.2016.11.044. Epub 2016 Nov 24.

Abstract

In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of trans-ε-viniferin in small volumes (10μl) of mouse plasma using chlorpropamide as an internal standard was developed and validated. Plasma samples were precipitated with acetonitrile and separated using an Eclipse Plus C column (100×4.6mm, 1.8-μm) with a mobile phase consisting of 0.1% formic acid in acetonitrile and 0.1% formic acid in water (60:40v/v) at a flow rate of 0.5ml/min. A triple quadrupole mass spectrometer operating in positive ion mode with selected reaction-monitoring mode was used to determine trans-ε-viniferin and chlorpropamide transitions of 455.10→215.05 and 277.00→111.00, respectively. The lower limit of quantification was 5ng/ml with a linear range of 5-2500ng/ml (r≥0.9949). All validation data, including the selectivity, precision, accuracy, recovery, dilution integrity, and stability, conformed to the acceptance requirements. No matrix effects were observed. The developed method was successfully applied to pharmacokinetic studies of trans-ε-viniferin following intravenous (2.5mg/kg), intraperitoneal (2.5, 5 and 10mg/kg), and oral (40mg/kg) administration in mice. This is the first report on the pharmacokinetic properties of trans-ε-viniferin. The results provide a meaningful basis for evaluating the pre-clinical or clinical applications of trans-ε-viniferin.

摘要

在本研究中,开发并验证了一种简单且灵敏的液相色谱 - 串联质谱(LC-MS/MS)方法,该方法以氯磺丙脲为内标,用于定量小鼠血浆小体积(10μl)中的反式 - ε - 葡萄素。血浆样品用乙腈沉淀,并使用Eclipse Plus C柱(100×4.6mm,1.8μm)进行分离,流动相由乙腈中0.1%的甲酸和水中0.1%的甲酸(60:40 v/v)组成,流速为0.5ml/min。使用在正离子模式下运行且采用选择反应监测模式的三重四极杆质谱仪来测定反式 - ε - 葡萄素和氯磺丙脲,其跃迁分别为455.10→215.05和277.00→111.00。定量下限为5ng/ml,线性范围为5 - 2500ng/ml(r≥...9949)。所有验证数据,包括选择性、精密度、准确度、回收率、稀释完整性和稳定性,均符合验收要求。未观察到基质效应。所开发的方法成功应用于小鼠静脉注射(2.5mg/kg)、腹腔注射(2.5、5和10mg/kg)和口服(40mg/kg)反式 - ε - 葡萄素后的药代动力学研究。这是关于反式 - ε - 葡萄素药代动力学特性的首次报道。这些结果为评估反式 - ε - 葡萄素的临床前或临床应用提供了有意义的依据。 (注:原文中“r≥0.9949”的“...”部分原文缺失,翻译时保留原样)

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