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液相色谱-串联质谱法测定大鼠血浆中抗癫痫药物拉科酰胺的含量及其在药代动力学研究中的应用。

Liquid chromatography-tandem mass spectrometry for quantification of lacosamide, an antiepileptic drug, in rat plasma and its application to pharmacokinetic study.

作者信息

Kim Soo-Jin, Koo Tae-Sung, Ha Dong-Jin, Baek Myoungki, Lee Sang-Kil, Shin Dong-Soo, Moon Hongsik

机构信息

Life Science R&D Park, SK Holdings Co. Ltd, Daejeon, 305-712, Korea.

出版信息

Biomed Chromatogr. 2012 Mar;26(3):371-6. doi: 10.1002/bmc.1668. Epub 2011 Jul 7.

DOI:10.1002/bmc.1668
PMID:21735462
Abstract

A rapid, simple and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) was developed for the determination of an antiepileptic drug, lacosamide, in rat plasma. The method involves the addition of acetonitrile and internal standard solution to plasma samples, followed by centrifugation. An aliquot of the supernatant was diluted with water and directly injected into the LC/MS/MS system. The separations were performed on column packed with octadecylsilica (5 µm, 2.0 × 50 mm) with 0.1% formic acid and acetonitrile as mobile phase, and the detection was performed on tandem mass spectrometry by the multiple-reaction monitoring via an electrospray ionization source. The standard curve was linear over the concentration range from 0.3 to 1000 ng/mL. The lower limit of quantification was 0.3 ng/mL using 50 μL of rat plasma sample. The intra- and inter-assay precision and accuracy were found to be less than 11.7 and 8.8%, respectively. The developed analytical method was successfully applied to the pharmacokinetic study of lacosamide in rats.

摘要

建立了一种快速、简便、灵敏的液相色谱-串联质谱法(LC/MS/MS),用于测定大鼠血浆中的抗癫痫药物拉科酰胺。该方法包括向血浆样品中加入乙腈和内标溶液,然后进行离心。取上清液的一份等分试样用水稀释,直接注入LC/MS/MS系统。采用十八烷基硅胶柱(5 µm,2.0×50 mm),以0.1%甲酸和乙腈为流动相进行分离,并通过电喷雾电离源采用多反应监测模式在串联质谱上进行检测。标准曲线在0.3至1000 ng/mL的浓度范围内呈线性。使用50 μL大鼠血浆样品时,定量下限为0.3 ng/mL。批内和批间精密度及准确度分别小于11.7%和8.8%。所建立的分析方法成功应用于拉科酰胺在大鼠体内的药代动力学研究。

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