LC/MS联用法测定人血浆中氟西汀的浓度

Determination of Fluoxetine in Human Plasma by LC/MS

目的：建立测定人血浆中氟西汀浓度的液／质联用方法。方法：以氯氮平为内标，血浆样品用饱和碳酸钠溶液碱化，经乙酸乙酯振荡萃取后，进样分析。其中色谱柱为C18，流动相为5mmol·L^-1乙酸铵溶液（0．5％乙酸）-甲醇-乙腈（42：22：36），流速为0．24mL·min^-1，柱温40℃；通过电喷雾离子化（ESI）质谱以扫描方式检测，选择性正离子监测质荷比（m／z）为310（氟西汀，M＋H）和327（内标，氯氮平，M＋H）。结果：氟西汀血浆药物浓度在0．5～100ng·mL^-1范围内线性关系良好（r=0．9986），最低定量浓度为0．5ng·mL^-1；方法回收率在96．0％-98．0％之间，日内、日间RSD均小于13％。结论：本方法简便、准确、灵敏度高，可用于临床氟西汀血药浓度的监测和药动学研究。

OBJECTIVE：To develop a high sensitive LC/MS method for the determination of fluoxetine in human plasma. METHODS： Fluoxetine and internal standard clozapine were extracted from plasma with ethyl acetate after being alkalized by sodium carbonate saturated solution. And the separation of fluoxetine was performed on C18 analytical column with column temperature at 40℃ .The mobile phase consisted of 5mmol· L^ -1 ammonium acetate（0.5% acetic acid） -methanol- acetonitrile （42 ： 22 ： 36） at a flow rate of 0.24mL · min^-1.A mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected ion monitoring（SIM） was performed and the m/s of ions selected for quantification were 310（fluoxetine, M ＋ H） and 327（internal standard, clozapine, M ＋ H） .RESULTS： The calibration curve was linear within the range of 0.5-100ng ·mL^-1（ r = 0.998 6）, with the minimum limit of quantification at 0.5ng·mL^-1.The recovery rate was 96.0%-98.0%, with both intra-day and inter- day at less than 13% .CONCLUSION： The method is rapid,sensitive and suitable for the monitoring of serum concentration and pharmacokinetics of fluoxetine.