一种通过液相色谱-串联质谱法测定大鼠干血斑中左乙拉西坦的简单分析方法。
A simple assay for determination of levetiracetam in rat dried blood spots by LC-MS/MS.
作者信息
Luo Wenxia, Kong Sing Teang, Yang Shili, Chan Bernice Choi Wai, Ho Paul C
机构信息
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543 Singapore.
出版信息
Bioanalysis. 2013 Aug;5(15):1843-51. doi: 10.4155/bio.13.143.
BACKGROUND
A simple LC-MS/MS method was developed and validated for the quantification of levetiracetam (LEV, Keppra®), a broad-spectrum antiepileptic drug (AED) in rat dried blood spots (DBS). LEV was simply extracted with methanol spiked with adenosine (ADE) as IS before LC-MS/MS analysis. The correlation between the DBS and plasma concentrations of LEV was also determined.
RESULTS
Linearity was from 0.067-60 µg/ml for LEV in DBS samples. The intra- and inter-day accuracy and precision of the assay met validation acceptance criteria. The developed assay was applied to monitor levetiracetam DBS levels in Sprague-Dawley rats after intravenous administration. DBS concentrations were well correlated to the plasma concentrations (R² = 0.9399), as fraction of LEV bound to blood cells remains very constant (0.466 ± 0.041) over a wide concentration range.
CONCLUSION
The study illustrated that DBS could be used as alternative matrix for monitoring LEV in preclinical studies.
背景
开发并验证了一种简单的液相色谱-串联质谱（LC-MS/MS）方法，用于定量测定大鼠干血斑（DBS）中广谱抗癫痫药物（AED）左乙拉西坦（LEV，开浦兰®）。在进行LC-MS/MS分析之前，用添加了腺苷（ADE）作为内标的甲醇简单提取LEV。还测定了LEV的DBS浓度与血浆浓度之间的相关性。
结果
DBS样品中LEV的线性范围为0.067 - 60 µg/ml。该测定方法的日内和日间准确性及精密度符合验证验收标准。所开发的测定方法用于监测静脉给药后Sprague-Dawley大鼠的左乙拉西坦DBS水平。DBS浓度与血浆浓度具有良好的相关性（R² = 0.9399），因为在很宽的浓度范围内，与血细胞结合的LEV比例保持非常恒定（0.466 ± 0.041）。
结论
该研究表明，在临床前研究中，DBS可作为监测LEV的替代基质。
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