用于定量测定人血浆中茴拉西坦的灵敏且选择性的液相色谱-串联质谱法。

Sensitive and selective liquid chromatography-tandem mass spectrometry method for the quantification of aniracetam in human plasma.

作者信息

Zhang Jingjing, Liang Jiabi, Tian Yuan, Zhang Zunjian, Chen Yun

机构信息

Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 15;858(1-2):129-34. doi: 10.1016/j.jchromb.2007.08.010. Epub 2007 Aug 21.

DOI:10.1016/j.jchromb.2007.08.010

PMID:17826366

Abstract

A rapid, sensitive and selective LC-MS/MS method was developed and validated for the quantification of aniracetam in human plasma using estazolam as internal standard (IS). Following liquid-liquid extraction, the analytes were separated using a mobile phase of methanol-water (60:40, v/v) on a reverse phase C18 column and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode using the respective [M+H]+ ions, m/z 220-->135 for aniracetam and m/z 295-->205 for the IS. The assay exhibited a linear dynamic range of 0.2-100 ng/mL for aniracetam in human plasma. The lower limit of quantification (LLOQ) was 0.2 ng/mL with a relative standard deviation of less than 15%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated LC-MS/MS method has been successfully applied to study the pharmacokinetics of aniracetam in healthy male Chinese volunteers.

摘要

建立了一种快速、灵敏且选择性高的液相色谱-串联质谱（LC-MS/MS）方法，并进行了验证，用于以艾司唑仑为内标（IS）定量测定人血浆中的茴拉西坦。液-液萃取后，使用甲醇-水（60:40，v/v）流动相在反相C18柱上分离分析物，并通过三重四极杆质谱仪在选择反应监测（SRM）模式下使用各自的[M+H]+离子进行分析，茴拉西坦的m/z为220→135，内标的m/z为295→205。该测定法在人血浆中茴拉西坦的线性动态范围为0.2 - 100 ng/mL。定量下限（LLOQ）为0.2 ng/mL，相对标准偏差小于15%。在标准曲线范围内的浓度获得了可接受的精密度和准确度。验证后的LC-MS/MS方法已成功应用于研究茴拉西坦在中国健康男性志愿者中的药代动力学。