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UHPLC-ESI-MS/MS 测定及口服延胡索提取物后大鼠血浆中两种生物碱成分的药代动力学研究。

UHPLC-ESI-MS/MS determination and pharmacokinetic study of two alkaloid components in rat plasma after oral administration of the extract of Corydalis bungeana Turcz.

机构信息

College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ 08854, USA.

College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 1;960:59-66. doi: 10.1016/j.jchromb.2014.04.009. Epub 2014 Apr 18.

Abstract

Corynoline and acetycorynoline are active compounds of Corydalis bungeana Turcz. with various pharmacological effects such as sedation, anti-leptospira and liver injury protection effects. A specific, simple and sensitive UHPLC-ESI-MS/MS method was developed and validated for the pharmacokinetic study of corynoline and acetycorynoline in rat plasma. Corynoline and acetycorynoline were extracted from plasma samples by liquid-liquid extraction. The analysis was carried out on an Agilent SB-C18 column (1.8 μm, 50 mm×2.1mm) with the mobile phase of acetonitrile-0.1% formic acid (80:20, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source in positive mode. The current UHPLC-ESI-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. The lower limits of quantification were 0.10 ng/mL for corynoline and 0.353 ng/mL for acetycorynoline. Intra-day and inter-day precision were less than 12.3% and accuracy ranged from 0.18% to 14.9%. The mean extraction recoveries of analytes and internal standard (IS) from rat plasma were all more than 76.2%. This validated method was successfully applied to pharmacokinetic study in rats after oral administration of corynoline, acetycorynoline and the extract of Corydalis bungeana Turcz.

摘要

刻叶紫堇灵和乙酰刻叶紫堇灵是紫堇属植物紫堇的活性化合物,具有镇静、抗钩端螺旋体和肝损伤保护等多种药理作用。本研究建立并验证了一种专属性强、简单、灵敏的 UHPLC-ESI-MS/MS 法,用于大鼠血浆中刻叶紫堇灵和乙酰刻叶紫堇灵的药代动力学研究。采用液-液萃取法从血浆样品中提取刻叶紫堇灵和乙酰刻叶紫堇灵。采用 Agilent SB-C18 柱(1.8μm,50mm×2.1mm),以乙腈-0.1%甲酸(80:20,v/v)为流动相进行梯度洗脱,在电喷雾正离子源(ESI)下,采用多反应监测(MRM)模式进行检测。本 UHPLC-ESI-MS/MS 分析方法进行了线性、日内和日间精密度、准确度、提取回收率和稳定性验证。刻叶紫堇灵和乙酰刻叶紫堇灵的定量下限分别为 0.10ng/mL 和 0.353ng/mL。日内和日间精密度均小于 12.3%,准确度在 0.18%至 14.9%范围内。分析物和内标(IS)从大鼠血浆中的平均提取回收率均大于 76.2%。该方法已成功应用于口服刻叶紫堇灵、乙酰刻叶紫堇灵和紫堇提取物后大鼠的药代动力学研究。

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