Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma
Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma
复制标题
DOI：
10.1016/j.jchromb.2007.09.021
复制
发表时间：
2007-11-01
影响因子：
3
通讯作者：
Batra, Vijay
中科院分区：
文献类型：
--
作者：
Paliwal, Jyoti;Batra, Vijay
建立了一种简便、灵敏、快速的液相色谱/串联质谱（LC-MS/MS）法，并以抗疟药哌喹的结构类似物哌喹氯喹啉为内标物，测定了哌喹的血药浓度。该方法包括用甲醇进行简单的蛋白质沉淀，然后在Chromolith，SpeedROD RP-18 e反相色谱柱上用10 MM乙酸铵缓冲液/甲醇/甲酸/氨溶液（25/75/0.2/0.15，v/v）快速等度洗脱分析物，并在多反应监测模式（MRM）下通过质谱法进行定量。分别使用m/z 535.3 -> 288.2和m/z 409.1 -> 205.2的前体至产物离子跃迁来测量分析物和IS。该测定法显示血浆中哌喹的线性动态范围为1.0-250.2 ng/mL。血浆中的检测限（LOD）和定量下限（LLOQ）分别为0.2和1.0 ng/mL。对于标准曲线范围内的浓度，获得了可接受的精密度和准确度（LLOQ标准品与相应标称浓度的偏差为+/- 20%，其他标准品与相应标称浓度的偏差为+/- 15%）。2.5分钟的样品运行时间使得每天分析超过400份血浆样品的通量成为可能。经验证的方法已成功应用于分析I期临床研究的人血浆样品。口服1000 mg后，哌喹的平均药代动力学参数：观察到的最大血浆浓度（C-max）、达峰时间（Tmax）和消除半衰期（T-1/2）分别为46.1 ng/mL、3.8 h和13天。(C)2007 Elsevier B. V.保留所有权利。
A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of piperaquine, an antimalarial drug, in human plasma using its structural analogue, piperazine his chloroquinoline as internal standard (IS). The method involved a simple protein precipitation with methanol followed by rapid isocratic elution of analytes with 10 MM ammonium acetate buffer/methanol/formic acid/ammonia solution (25/75/0.2/0.15, v/v) on Chromolith,SpeedROD RP-18e reversed phase chromatographic column and quantification by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 535.3 -> 288.2 and mlz 409.1 -> 205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 1.0-250.2 ng/mL for piperaquine in plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) in plasma were 0.2 and 1.0 ng/mL, respectively. Acceptable precision and accuracy (+/- 20% deviation for LLOQ standard and +/- 15% deviation for other standards from the respective nominal concentration) were obtained for concentrations over the standard curve ranges. A run time of 2.5 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully applied to analyze human plasma samples from phase-1 clinical studies. The mean pharmacokinetic parameters of piperaquine following 1000 mg oral dose: observed maximum plasma concentration (C-max), time to maximum plasma concentration (T-max) and elimination half-life (T-1/2) were 46.1 ng/mL, 3.8 h and 13 days, respectively. (C) 2007 Elsevier B.V. All rights reserved.