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口服千知胶囊后超高效液相色谱-电喷雾串联质谱法同时测定大鼠血浆中 4 种醌类成分及其药代动力学研究

Simultaneous determination and pharmacokinetics study of four quinones in rat plasma by ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry after the oral administration of Qianzhi capsules.

机构信息

College of Pharmacy, Harbin Medical University, Harbin, P.R. China.

Key Laboratory of Chinese Materia Medical (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China.

出版信息

J Sep Sci. 2018 May;41(10):2161-2168. doi: 10.1002/jssc.201700981. Epub 2018 Mar 12.

DOI:10.1002/jssc.201700981
PMID:29436170
Abstract

A sensitive, specific, and accurate ultra high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous quantification of purpurin, munjistin, mollugin, and alizarin from Qianzhi capsules in rat plasma. Chromatographic separation was performed on an Agilent Eclipse Plus C RRHD column with a mobile phase consisting of methanol and 5 mM ammonium acetate/water with gradient elution. The analytes were quantified on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring mode and switching the electrospray ion source polarity with positive electrospray ionization in a single run. Samples were pretreated by liquid-liquid extraction with cyclohexane. The intra- and interday precision and accuracy of the assay were within acceptable ranges. Matrix effects for all of the analytes were between 90.16 and 100.21%. The average recovery ranged from 75.38 to 88.96%. This method was successfully applied to study the pharmacokinetic parameters of the four compounds in rat plasma after oral administration of Qianzhi capsules. Four quinones could be rapidly absorbed into blood (t , 0.80-1.93 h) and eliminated relatively slowly (t , 8.07-11.97 h). The results might be helpful for guiding the clinical application of Qianzhi capsules in the future.

摘要

建立并验证了一种灵敏、特异、准确的超高效液相色谱-电喷雾串联质谱法,用于同时定量测定千知胶囊在大鼠血浆中的紫堇灵、木兰花碱、羟基茜草素和茜素。色谱分离在 Agilent Eclipse Plus C RRHD 柱上进行,流动相由甲醇和 5 mM 乙酸铵/水组成,采用梯度洗脱。分析物在三重四极杆质谱仪上进行定量分析,采用正离子电喷雾电离切换电喷雾离子源极性的多反应监测模式进行单运行。样品通过环己烷液-液萃取预处理。该测定方法的日内和日间精密度和准确度均在可接受范围内。所有分析物的基质效应均在 90.16%至 100.21%之间。平均回收率在 75.38%至 88.96%之间。该方法成功应用于研究千知胶囊灌胃给药后大鼠血浆中四种化合物的药代动力学参数。四种醌类化合物能迅速被血液吸收(t 1/2 ,0.80-1.93 h),消除相对较慢(t 1/2 ,8.07-11.97 h)。结果可能有助于指导千知胶囊在未来的临床应用。

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