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GC-MS/MS 法测定大鼠血浆中 α-雪松烯的含量及其药代动力学应用。

GC-MS/MS method for the quantification of α-cedrene in rat plasma and its pharmacokinetic application.

机构信息

Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon, Korea; College of Pharmacy, Kyung Hee University, Seoul, Korea.

出版信息

J Sep Sci. 2013 Nov;36(21-22):3558-62. doi: 10.1002/jssc.201300828. Epub 2013 Sep 18.

DOI:10.1002/jssc.201300828
PMID:23996797
Abstract

α-Cedrene is a pharmacologically active ingredient isolated from the essential oil of cedar. A selective and sensitive GC-MS/MS method was developed for the quantification of α-cedrene in rat plasma for the first time. α-Cedrene was extracted from rat plasma using ethyl acetate at neutral pH. The analytes were determined in selective reaction monitoring mode using MS/MS: m/z 204.3→119.0 for α-cedrene and m/z 146.0→111.0 for 1,4-dichlorobenzene (internal standard). The standard curve was linear (r(2) ≥ 0.995) over the concentration ranges of 5-800 ng/mL. The lower limit of quantification was 5 ng/mL using 50 μL of rat plasma. The coefficient of variation and relative error for intra- and interassays at four quality control levels were 3.1-13.9% and -4.0-2.6%, respectively. The stability of processing (freeze-thaw, long-term storage at -80°C, and short-term storage at room temperature) and chromatography (reinjection) was shown to be of insignificant effect. The present method was applied successfully to the pharmacokinetic study of α-cedrene after its intravenous (10 mg/kg) and oral (25 mg/kg) administration in male Sprague-Dawley rats.

摘要

α-雪松烯是从雪松精油中分离得到的一种具有药理活性的成分。首次建立了一种用于定量检测大鼠血浆中 α-雪松烯的选择性和灵敏性 GC-MS/MS 方法。采用乙酸乙酯在中性 pH 条件下从大鼠血浆中提取 α-雪松烯。采用 MS/MS 在选择反应监测模式下对分析物进行测定:m/z 204.3→119.0 用于 α-雪松烯,m/z 146.0→111.0 用于 1,4-二氯苯(内标)。标准曲线在 5-800ng/mL 浓度范围内呈线性(r(2)≥0.995)。使用 50μL 大鼠血浆,定量下限为 5ng/mL。四个质控水平的日内和日间精密度和准确度的变异系数和相对误差分别为 3.1-13.9%和-4.0-2.6%。处理(冻融、-80°C 长期储存和室温短期储存)和色谱(再进样)的稳定性表明无显著影响。该方法成功应用于雄性 Sprague-Dawley 大鼠静脉(10mg/kg)和口服(25mg/kg)给予 α-雪松烯后的药代动力学研究。

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