A New Rapid and Sensitive LC-MS Assay for the Determination of Sorafenib in Plasma: Application to a Patient Undergoing Hemodialysis
A New Rapid and Sensitive LC-MS Assay for the Determination of Sorafenib in Plasma: Application to a Patient Undergoing Hemodialysis
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DOI：
10.1097/ftd.0b013e3182357891
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发表时间：
2011-12-01
影响因子：
2.5
通讯作者：
Bard, Jean-Marie
中科院分区：
文献类型：
--
作者：
Bobin-Dubigeon, Christine;Heurgue-Berlot, Alexandra;Bard, Jean-Marie
开发并验证了一种简单的液相色谱-质谱法用于人血浆中索拉非尼（Nexavar）的定量。固相萃取程序后，使用由甲酸/乙腈组成的移动的流动相的等度流在2分钟内进行分离，该流动相应用于C18分析柱上。在单离子监测模式下通过质谱法检测分析物。根据美国食品药品监督管理局的建议对该方法进行了验证。方法在10 ~ 10000 ng/mL范围内线性关系良好（r（2）>0.99）。检测和定量下限分别为5和10 ng/mL。日内和日间不精密度小于10.4%，不准确度不超过8.7%。平均提取回收率为92.2%。该方法在时间稳定性和稀释完整性方面也提供了令人满意的结果。研究患者的索拉非尼血浆浓度范围为1831 - 3459 ng/mL。这种新技术是快速，灵敏，并应用于血液透析患者索拉非尼血药浓度的测定。我们的研究结果表明，索拉非尼不能通过血液透析从血浆中清除，尽管透析后应延迟分析以避免不稳定的波动。
A simple liquid chromatography-mass spectrometry method was developed and validated for quantification of sorafenib (Nexavar) in human plasma. After a solid-phase extraction procedure, the separation was performed within 2 minutes using an isocratic flow of a mobile phase consisting of formic acid/acetonitrile applied on a C18 analytical column. The analyte was detected by mass spectrometry in the single-ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r(2)>0.99) between 10 and 10,000 ng/mL. The lower limits of detection and quantification were 5 and 10 ng/mL, respectively. Within-day and between-day imprecisions were less than 10.4%, and inaccuracy did not exceed 8.7%. The mean extraction recovery was 92.2%. The method also provided satisfactory results in terms of time stability and dilution integrity. Sorafenib plasma concentrations of the studied patient ranged between 1831 and 3459 ng/mL. This new technique is rapid, sensitive, and was applied to the determination of sorafenib plasma concentrations in a patient undergoing hemodialysis. Our results indicate that sorafenib is not cleared from plasma by hemodialysis, although analysis should be delayed after dialysis to avoid erratic fluctuations.