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LC-MS/MS 测定及口服刺五加提取物后大鼠血浆中四种木脂素成分的药代动力学研究。

LC-MS/MS determination and pharmacokinetic study of four lignan components in rat plasma after oral administration of Acanthopanax sessiliflorus extract.

机构信息

Department of Analytical Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.

出版信息

J Ethnopharmacol. 2012 Jun 14;141(3):957-63. doi: 10.1016/j.jep.2012.03.034. Epub 2012 Apr 4.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Acanthopanax sessiliflorus (Rupr. et Maxim.) Seem. is a shrub mainly present in China, Japan and Korea, the root bark of which is considered as one of the sources of Wujiapi and widely used for its various pharmacological effects.

AIM OF THE STUDY

A selective and sensitive UPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of asarinin, sesamin, helioxanthin and savinin in rat plasma.

MATERIALS AND METHODS

Sample preparation involved a liquid-liquid extraction of the analytes with methyl tert-butyl ether (MTBE). LC separation was achieved on a UPLC C(18) column at 30°C with a mobile phase consisting of methanol-2 mM ammonium acetate (68:32, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning with electrospray ionization (ESI) source operating in the positive ionization mode. The optimized mass transition ion-pairs (m/z) monitored for asarinin, sesamin, helioxanthin, savinin and IS were 372.2/233.0, 372.2/233.0, 349.1/319.0, 352.9/334.9 and 180.0/109.7, respectively.

RESULTS

The current LC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability and was suitable for pharmacokinetic studies of the four lignans after oral administration of Acanthopanax sessiliflorus extract. The time to reach the maximum plasma concentration (T(max)) was 2.50±0.15 h for asarinin, 1.94±0.28 for sesamin, 2.22±0.48 h for helioxanthin and 2.83±0.29 h for savinin. The elimination half-time (t(1/2)) of asarinin, sesamin, helioxanthin and savinin was 6.08±1.10, 11.69±0.50, 7.16±0.52 and 6.26±0.57 h, respectively.

CONCLUSION

This paper described a simple, sensitive and validated UPLC-MS/MS method for simultaneous determination of four lignans in rat plasma after oral administration of Acanthopanax sessiliflorus extract, and investigated on their pharmacokinetic studies as well.

摘要

民族药理学相关性

刺五加(Rupr. et Maxim.)是一种灌木,主要分布在中国、日本和韩国,其根皮被认为是五加皮的来源之一,具有多种药理作用,被广泛应用。

目的

建立并验证一种选择性和灵敏的 UPLC-MS/MS 方法,用于测定大鼠血浆中土木香内酯、芝麻素、银杏黄素和 savinin 的浓度并进行药代动力学研究。

材料和方法

样品制备采用甲基叔丁基醚(MTBE)进行液液萃取。LC 分离在 30°C 下采用 UPLC C(18)柱进行,流动相由甲醇-2 mM 乙酸铵(68:32,v/v)组成。检测采用电喷雾电离(ESI)源在正离子模式下进行多反应监测(MRM)扫描。监测到土木香内酯、芝麻素、银杏黄素、 savinin 和内标(IS)的优化质量转换离子对(m/z)分别为 372.2/233.0、372.2/233.0、349.1/319.0、352.9/334.9 和 180.0/109.7。

结果

当前的 LC-MS/MS 分析方法具有良好的线性、日内和日间精密度、准确度、提取回收率和稳定性,适用于口服刺五加提取物后四种木脂素的药代动力学研究。土木香内酯、芝麻素、银杏黄素和 savinin 的达峰时间(T(max))分别为 2.50±0.15 h、1.94±0.28 h、2.22±0.48 h 和 2.83±0.29 h。土木香内酯、芝麻素、银杏黄素和 savinin 的半衰期(t(1/2))分别为 6.08±1.10 h、11.69±0.50 h、7.16±0.52 h 和 6.26±0.57 h。

结论

本文描述了一种简单、灵敏和经过验证的 UPLC-MS/MS 方法,用于测定口服刺五加提取物后大鼠血浆中四种木脂素的浓度,并对其药代动力学研究进行了探讨。

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