A simple assay for determination of levetiracetam in rat dried blood spots by LC-MS/MS

作者：Luo Wenxia; Kong Sing Teang; Yang Shili; Chan Bernice Choi Wai; Ho Paul C^*

来源：Bioanalysis, 2013, 5(15): 1843-1851.

DOI：10.4155/bio.13.143

Background: A simple LC-MS/MS method was developed and validated for the quantification of levetiracetam (LEV, Keppra((R))), 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 mu g/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 (R-2 = 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.