Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry
Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry
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等度液相色谱串联质谱法同时测定人血浆中丙氯拉嗪及其代谢物
DOI：
10.1002/bmc.1725
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发表时间：
2012
影响因子：
1.8
通讯作者：
Kawakami J
中科院分区：
文献类型：
--
作者：
Tashiro M;Naito T;Kagawa Y;Kawakami J
口服异丙嗪(PCZ)是一种止吐剂，它经历了广泛的首过代谢。建立了人血浆中PCZ及其主要代谢物异丙嗪(PCZSO)、N-去甲基异丙嗪(NDPCZ)和7-羟基异丙嗪(PCZOH)的LC-MS/MS同时分析方法。去蛋白血浆样品用3 µm十八烷基硅烷色谱柱分离，运行时间为10 min。多氯联苯、邻苯二甲酸二恶英和多氯联苯的线性范围为0.0 1~40 微克/L，二恶英的线性范围为0.0 5~80 微克/L。批内和批间精密度分别为7.0%和99-104%，精密度为9.0%和99-105%。血药浓度的下限为10 ng/L，50 ng/L。将该方法应用于37例接受PCZ治疗的癌症患者的血浆样品测定。PCZ、PCZSO、NDPCZ和PCZOH的血药浓度个体间差异较大(RSD分别为89.4、88.7、86.4和78.2%)。结论：该LC-MS/MS联用方法分析性能良好，可用于评价PCZ的药代动力学，包括其在癌症患者体内代谢物的测定和临床研究。版权所有©2011 John Wiley&Sons，Ltd.
Oral prochlorperazine (PCZ), an antiemetic, undergoes extensive first‐pass metabolism. The study developed a simultaneous analytical method for PCZ and its major metabolites, prochlorperazine sulfoxide (PCZSO),N‐demethylprochlorperazine (NDPCZ) and 7‐hydroxyprochlorperazine (PCZOH), in human plasma using an isocratic liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method. Deproteinized plasma specimens were separated using a 3 µm particle size octadecylsilyl column, and the run time was 10 min. The calibration curves were linear over the concentration ranges of 0.01–40 µg/L for PCZ, NDPCZ and PCZOH, and 0.05–80 µg/L for PCZSO. The intra‐ and inter‐assay precisions and accuracies were within 7.0 and 99–104% and within 9.0 and 99–105%, respectively. The lower limits of quantification in human plasma were 10 ng/L for PCZ, NDPCZ and PCZOH, and 50 ng/L for PCZSO. The validated method was applied to the determination of plasma samples in 37 cancer patients receiving PCZ. Large interindividual variations were observed in plasma concentrations of PCZ, PCZSO, NDPCZ and PCZOH (relative standard deviation, 89.4, 88.7, 86.4 and 78.2%, respectively). In conclusion, this simultaneous LC‐MS/MS method with acceptable analytical performance can be helpful for evaluating the pharmacokinetics of PCZ, including the determination of its metabolites in cancer patients and in clinical research. Copyright © 2011 John Wiley & Sons, Ltd.