Simultaneous quantitative analysis of fasudil and its active metabolite in human plasma by liquid chromatography electro-spray tandem mass spectrometry
Simultaneous quantitative analysis of fasudil and its active metabolite in human plasma by liquid chromatography electro-spray tandem mass spectrometry
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DOI：
10.1016/j.jpba.2009.12.028
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发表时间：
2010-06-05
影响因子：
3.4
通讯作者：
Wen, Shaojun
中科院分区：
文献类型：
--
作者：
Chen, Huaying;Lin, Yang;Wen, Shaojun
本研究开发并验证了一种使用 HPLC-MS/MS 快速、灵敏地定量人血浆中盐酸法舒地尔 (FH) 及其活性代谢物羟基法舒地尔 (M3) 的方法。该方法涉及简单的样品制备，使用甲醇作为蛋白质沉淀（3:1，v/v），雷尼替丁作为内标（IS）。使用梯度洗脱程序在分析柱 ZORBAX StableBond-C18（5 μm，150 mm x 4.6 mm）上分离分析物和内标。通过配备有正离子模式的 Turbo IonSpray 电离源的 AB 3200 QTRAP 串联质谱仪进行检测。使用产物离子前体的多反应监测 (MRM) 法舒地尔的 m/z 292.2/99.2，M3 的 m/z 308.2/99.2，IS 的 m/z 315.3/176.2。对于法舒地尔和 M3，该方法的线性范围均为 0.4 至 250 ng/mL。法舒地尔和 M3 的定量下限均为 0.4 ng/mL。在整个浓度范围内，法舒地尔的日内和日间相对标准偏差分别小于 7.11%，M3 的日内和日间相对标准偏差分别小于 10.6%。该方法已成功应用于12名健康中国志愿者连续静脉滴注30mg盐酸法舒地尔30min后的药代动力学评价。 (C) 2009 Elsevier B.V. 保留所有权利。
A fast and sensitive method to quantify fasudil hydrochloride (FH) and its active metabolite hydroxyfasudil (M3) in human plasma using HPLC-MS/MS has been developed and validated in present study. The method involved simple sample preparation with methanol as protein precipitation (3:1, v/v) and ranitidine as an internal standard (IS). The analytes and IS were separated using a gradient elution procedure on the analytical column ZORBAX StableBond-C18 (5 mu m, 150 mm x 4.6 mm). Detection was performed by an AB 3200 QTRAP tandem mass spectrometer equipped with a Turbo IonSpray ionization source set in positive ion mode. Multiple reaction monitoring (MRM) using the precursor to product ion was m/z 292.2/99.2 for fasudil, m/z 308.2/99.2 for M3 and m/z for 315.3/176.2 for IS. The linear range of the method was from 0.4 to 250 ng/mL for both fasudil and M3. The lower limit of quantification was 0.4 ng/mL for both fasudil and M3. The intra- and inter-day relative standard deviation over the entire concentration range was less than 7.11% for fasudil and 10.6% for M3, respectively. The validated method was Successfully applied for the evaluation of pharmacokinetic of fasudil hydrochloride after administration of 30 mg fasudil hydrochloride by continuous intravenous infusion over 30 min in 12 healthy Chinese volunteers. (C) 2009 Elsevier B.V. All rights reserved.