Microdose clinical trial: Quantitative determination of fexofenadine in human plasma using liquid chromatography/electro spray ionization tandem mass spectrometry
Microdose clinical trial: Quantitative determination of fexofenadine in human plasma using liquid chromatography/electro spray ionization tandem mass spectrometry
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DOI：
10.1016/j.jchromb.2007.08.011
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发表时间：
2007-10-15
影响因子：
3
通讯作者：
Kumagai, Yuji
中科院分区：
文献类型：
--
作者：
Yamane, Naoe;Tozuka, Zenzaburou;Kumagai, Yuji
建立了一种用于人体血浆中非索非那定定量测定的样品处理程序和高灵敏度液相色谱/电喷雾串联质谱（LC/ESI-MS/MS）方法，用于感冒药的微剂量临床试验，即，一种非放射性同位素标记的药物使用96孔固相萃取板（Oasis HLB）从血浆样品中提取非索非那定和特非那定（作为内标）。在ACQUITY UPLC系统和API 5000质谱仪上通过多反应监测进行定量。在XBridge C18柱（100 mm x 2.1 mm i.d.，粒径3.5 μ m），使用乙腈/2 mM乙酸铵（91：9，v/v）作为移动的相，流速为0.6 ml/min。根据FDA生物分析方法验证指南对分析方法进行验证。使用200 μ l血浆，校准曲线在10-1000 pg/ml范围内呈线性。还进行了临床剂量的分析方法验证，其中使用20 μ l血浆，校准曲线在1-500 ng/ml范围内呈线性。在8名健康志愿者中给予微量（100 μ g溶液）和临床剂量（60 mg剂量）后，使用LC/ESI-MS/MS成功应用每种方法进行血浆测定。(C)2007 Elsevier B. V.保留所有权利。
A sample treatment procedure and high-sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESl-MS/MS) method for quantitative determination of fexofenadine in human plasma was developed for a microdose clinical trial with a cold drug, i.e., a non-radioisotope-labeled drug. Fexofenadine and terfenadine, as internal standard, were extracted from plasma samples using a 96-well solid-phase extraction plate (Oasis HLB). Quantitation was performed on an ACQUITY UPLC system and an API 5000 mass spectrometer by multiple reaction monitoring. Chromatographic separation was achieved on an XBridge C 18 column (100 mm x 2.1 mm i.d., particle size 3.5 mu n) using acetonitrile/2 mM ammonium acetate (91:9, v/v) as the mobile phase at a flow rate of 0.6 ml/min. The analytical method was validated in accordance with the FDA guideline for validation of bioanalytical methods. The calibration curve was linear in the range of 10-1000 pg/ml using 200 mu l of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 1-500 ng/ml using 20 mu l of plasma, was also conducted. Each method was successfully applied for making determinations in plasma using LC/ESI-MS/MS after administration of a microdose (100 mu g solution) and a clinical dose (60 mg dose) in eight healthy volunteers. (C) 2007 Elsevier B.V. All rights reserved.