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采用液相色谱-串联质谱法研究丹参酮IIA在大鼠体内的组织分布

Study of tanshinone IIA tissue distribution in rat by liquid chromatography-tandem mass spectrometry method.

作者信息

Bi Hui-chang, Law Francis C P, Zhong Guo-ping, Xu Chen-shu, Pan Ying, Ding Liang, Chen Xiao, Zhao Li-zi, Xu Qiong, Huang Min

机构信息

Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, People's Republic of China.

出版信息

Biomed Chromatogr. 2007 May;21(5):473-9. doi: 10.1002/bmc.778.

Abstract

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for determining tanshinone IIA in rat tissues. After a single step liquid-liquid extraction with diethyl ether, tanshinone IIA and loratadine (internal standard) was subjected to LC/MS/MS analysis using positive electro-spray ionization under selected reaction monitoring mode. Chromatographic separation of tanshinone IIA and loratadine was achieved on a Hypersil BDS C(18) column (i.d. 2.1 x 50 mm, 5 microm) with a mobile phase consisting of methanol-1% formic acid (90:10, v/v) at a flow rate of 300 microL/min. The intra-day and inter-day precision of the method were less than 10.2 and 12.4%, respectively. The intra-day and inter-day accuracies ranged from 99.7 to 109.7%. The lowest limit of quantification for tanshinone IIA was 1 ng/mL. The method was applied to a tanshinone IIA tissue distribution study after an oral dose of 60 mg/kg to rats. Tanshinone IIA tissue concentrations decreased in the order of stomach > small intestine > lung > liver > fat > muscle > kidneys > spleen > heart > plasma > brain > testes. Tanshinone IIA still could be detected in most of the tissues at 20 h post-dosing. These results indicate that the LC/MS/MS method was rapid and sensitive to quantify tanshinone IIA in different rat tissues.

摘要

建立并验证了一种液相色谱/串联质谱(LC/MS/MS)法,用于测定大鼠组织中的丹参酮IIA。用乙醚进行单步液-液萃取后,将丹参酮IIA和氯雷他定(内标)在选择反应监测模式下采用正电喷雾电离进行LC/MS/MS分析。在Hypersil BDS C(18)柱(内径2.1×50 mm,5μm)上实现了丹参酮IIA和氯雷他定的色谱分离,流动相为甲醇-1%甲酸(90:10,v/v),流速为300μL/min。该方法的日内和日间精密度分别小于10.2%和12.4%。日内和日间准确度范围为99.7%至109.7%。丹参酮IIA的最低定量限为1 ng/mL。该方法应用于大鼠口服60 mg/kg剂量后的丹参酮IIA组织分布研究。丹参酮IIA在各组织中的浓度顺序为胃>小肠>肺>肝>脂肪>肌肉>肾>脾>心>血浆>脑>睾丸。给药后20小时,大多数组织中仍可检测到丹参酮IIA。这些结果表明,LC/MS/MS法可快速、灵敏地定量测定大鼠不同组织中的丹参酮IIA。

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