在线固相萃取液相色谱-三重四极杆/线性离子阱质谱法同时测定人血浆中4种抗抑郁药的含量

目的：建立在线固相萃取液相色谱-串联质谱同时测定人血浆中奥氮平、舍曲林、利培酮以及阿立哌唑4种抗抑郁药含量的检测方法。方法：用乙腈沉淀蛋白提取目标化合物，HySphere C₁₈在线固相净化柱净化，CAPCELL PAK C₁₈色谱柱分离，串联质谱采用电喷雾多反应监测正离子扫描模式进行检测，同位素内标法定量。结果：奥氮平、舍曲林、利培酮以及阿立哌唑4种抗抑郁药质量浓度在0.5～500 ng·mL^-1范围内线性关系良好，相关系数（r）均大于0.998，3个加样水平下的平均回收率为90.0%～97.3%，RSD（n=6）为2.1%～9.9%，准确度为92.0%～102.8%，4种药物在患者样品中的检测下限为2 ng·mL^-1。结论：该方法简单，准确度高，灵敏度好，可用于奥氮平、舍曲林、利培酮和阿立哌唑血药浓度的快速同时测定。

Objective: To develop a new method using online solid-phase extraction (SPE) liquid chromatography combined with tandem mass spectrometry (MS/MS) for the determination of olanzapine,sertraline,risperidone and aripiprazole in human plasma. Methods: The plasma sample was precipitated with acetonitrile. The analytes in extract were on-line purified directly on HySphere C₁₈ purification column where the sample matrices were washed away. Subsequently,the analytes which were eluted from the extraction column onto CAPCELL PAK C₁₈ column were separated with a gradient elution,and detected with electrospray ionization mass spectrometry in the positive scan mode using multiple reaction monitoring. The isotope internal standards were employed for quantification. Results: The concentrations of olanzapine,sertraline,risperidone and aripiprazole were in the range of 0.5-500 ng·mL^-1,respectively. The linear correlation coefficient(r)was greater than 0.998.Average recoveries of the analytes at three spiked concentration levels ranged from 90.0% to 97.3%,with relative standard deviations of 2.1% to 9.9%. The accuracy of four antidepressants was within the range of 92.0%-102.8%. The determination limit of four drugs in patient sample is 2 ng·mL^-1. Conclusion: The method is simple,accurate and specific,and can be used for rapid simultaneous determination of plasma concentration of olanzapine,sertraline,risperidone and aripiprazole.

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