Buspirone, fexofenadine, and omeprazole: quantification of probe drugs and their metabolites in human plasma.
Buspirone, fexofenadine, and omeprazole: quantification of probe drugs and their metabolites in human plasma.
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丁螺环酮、非索非那定和奥美拉唑：人血浆中探针药物及其代谢物的定量。
DOI：
10.1016/j.jpba.2011.03.043
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发表时间：
2011
影响因子：
3.4
通讯作者：
Reed,GregoryA
中科院分区：
文献类型：
--
作者：
Gor,Parul;Alnouti,Yazen;Reed,GregoryA
探针药物是用于测量人类受试者中药物代谢和转运活性的关键工具。通常，几种探针药物以“鸡尾酒”形式同时施用。这种鸡尾酒方法需要有效的分析方法来同时定量多种分析物。我们建立了一种液相色谱-串联质谱法同时测定人血浆中三种探针药物及其代谢物的方法。分析物包括奥美拉唑及其代谢物奥美拉唑砜和5′-羟基奥美拉唑;丁螺环酮及其代谢物1-[2-嘧啶基]-哌嗪（1 PP）;和非索非那定。使用乙腈蛋白沉淀法从血浆中提取这些分析物和内标兰索拉唑。使用7.5 mM碳酸氢铵和乙腈进行梯度反相色谱，并在阳离子电喷雾模式下使用多反应监测对分析物进行定量。对该方法进行了验证，以定量奥美拉唑、奥美拉唑砜、5′-羟基奥美拉唑和非索非那定的浓度范围为1.0-1000 ng/ml;丁螺环酮为0.1-100 ng/ml，1 PP为1.0-100 ng/ml。这些线性范围涵盖探针药物研究中所有分析物的血浆浓度。所有分析物的日内精密度为2.1%至16.1%，准确度为86%至115%。日间精密度和准确度范围分别为0.3 - 14%和90 - 110%。丁螺环酮的定量下限为0.1 ng/ml，所有其他分析物的定量下限为1 ng/ml。该方法提供了一种快速、灵敏和选择性的分析工具，用于定量血浆中的六种分析物，以支持在临床研究中使用该探针药物鸡尾酒。
Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a “cocktail”. This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography–tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5′-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5 mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0–1000 ng/ml for omeprazole, omeprazole sulfone, 5′-hydroxyomeprazole, and fexofenadine; 0.1–100 ng/ml for buspirone, and 1.0–100 ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 and 16.1%, and the accuracy ranged from 86 to 115% for all analytes. Inter-day precision and accuracy ranged from 0.3 to 14% and from 90 to 110%, respectively. The lower limits of quantification were 0.1 ng/ml for buspirone and 1 ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies.
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