HPLC-MS/MS快速测定人血浆中奥司他韦和羧酸奥司他韦的浓度

目的建立高效液相色谱联用质谱测定人血浆中奥司他韦和羧酸奥司他韦浓度的方法。方法内标选用奥司他韦-d₃和羧酸奥司他韦-d₃,血浆样品处理采用甲醇直接沉淀蛋白的方法,色谱柱为Venusil C₁₈Plus,2.1 mm×50.0 mm,5.0μm,以含0.1%乙酸水溶液和纯乙腈为流动相,梯度洗脱;应用电喷雾离子化,正离子模式下进行多反应监测奥司他韦(m/z 313→166)羧酸奥司他韦(m/z 285→197)和内标奥司他韦-d₃(m/z 285→138)和羧酸奥司他韦-d₃(m/z 339→251)。结果奥司他韦和羧酸奥司他韦分别在0.05~180 ng·m L^-1,4~720 ng·m L^-1,范围内线性关系良好,平均方法回收率均大于90%,日内及日间RSD均小于15%,稳定性考察结果良好。结论该方法灵敏、准确、简单、快速,可用于临床血药浓度检测和药动学研究。

HPLC-MS/MS Rapid Determination of Oseltamivir and Oseltamivir Carboxylic Acid in Human Plasma

OBJECTIVE To establish a HPLC method for the determination of oseltamivir and oseltamivir carboxylic acid in human plasma.METHODS The internal standard method was selected to detected oseltamivir-d₃and oseltamivir-d.The plasma samples were treated by direct precipitation of protein with methanol.The chromatographic column was Venusil C₁₈Plus(2.1 mm×50.0mm,5.0μm)with aqueous solution containing 0.1%acetic acid for 5 mmol·L-1and pure acetonitrile as mobile phase and gradient elution.Electrospray ionization was used to performed multi-reaction monitoring of oseltamivir(m/z 313→166)oseltamivir carboxylate(m/z 285→197)and oseltamivir-d₃with internal standard(m/z 285→138)and oseltamivir carboxylic acid-d₃(m/z 339→251)by positive ion mode.RESULTS The linear relationship between oseltamivir and oseltamivir were good at the range of 0.05~180 ng·m L^-1,4~720 ng·m L^-1.respectively.The average sample recovery was more than 90%for two analytes.The RSD of intra-day and inter-day were less than 15%.And the stability results were good.CONCLUSION This method is sensitive,accurate,simple and rapid,and can be used in clinical blood concentration detection and pharmacokinetic study.