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采用液相色谱-串联质谱法对大鼠血浆中大戟醇进行定量测定及其在药代动力学研究中的应用。

Quantitative determination of euphol in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

作者信息

Xie Xu, Li Yongning, Gao Dongna, Zhang Yu, Ren Yanbo

出版信息

Biomed Chromatogr. 2014 Sep;28(9):1229-34. doi: 10.1002/bmc.3151.

DOI:10.1002/bmc.3151
PMID:25237707
Abstract

Euphol is a potential pharmacologically active ingredient isolated from Euphorbia kansui. A simple, rapid, and sensitive method to determine euphol in rat plasma was developed based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the first time. The analyte and internal standard (IS), oleanic acid, were extracted from plasma with methanol and chromatographied on a C18 short column eluted with a mobile phase of methanol–water–formic acid (95:5:0.1, v/v/v). Detection was performed by positive ion atmospheric pressure chemical ionization in selective reaction monitoring mode. This method monitored the transitions m/z 409.0 →109.2 and m/z 439.4 → 203.2 for euphol and IS, respectively. The assay was linear over the concentration range 27–9000 ng/mL, with a limit of quantitation of 27 ng/mL. The accuracy was between –7.04 and 4.11%, and the precision was <10.83%. This LC-MS/MS method was successfully applied to investigate the pharmacokinetic study of euphol in rats after intravenous (6 mg/kg) and oral (48 mg/kg) administration. Results showed that the absolute bioavailability of euphol was approximately 46.01%.

摘要

大戟醇是从甘遂中分离出的一种具有潜在药理活性的成分。首次基于液相色谱-串联质谱法(LC-MS/MS)开发了一种简单、快速且灵敏的测定大鼠血浆中大戟醇的方法。分析物和内标(IS)齐墩果酸用甲醇从血浆中提取,并在C18短柱上进行色谱分离,流动相为甲醇-水-甲酸(95:5:0.1,v/v/v)。采用正离子大气压化学电离在选择性反应监测模式下进行检测。该方法分别监测大戟醇和内标的m/z 409.0→109.2和m/z 439.4→203.2的跃迁。该测定在27–9000 ng/mL的浓度范围内呈线性,定量限为27 ng/mL。准确度在–7.04%至4.11%之间,精密度<10.83%。该LC-MS/MS方法成功应用于研究大戟醇在大鼠静脉注射(6 mg/kg)和口服(48 mg/kg)给药后的药代动力学研究。结果表明,大戟醇的绝对生物利用度约为46.01%。

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