液相色谱-串联质谱法同时测定人血清中5种精神类药物的浓度

Simultaneous determination of five psychiatric drugs concentration in human serum by HPLC-MS/MS

目的建立一种同时测定人血清中5种精神类药物(奥氮平、利培酮、阿立哌唑、舍曲林和米氮平)浓度的液相色谱-串联质谱(HPLC-MS/MS)方法。方法以[2H3]-盐酸舍曲林为内标,用蛋白沉淀法处理样本。色谱柱:Kinetex?C18 LC Column (50. 0 mm×3. 0 mm,2. 6μm),流动相:5 mmol·L-1醋酸铵溶液-甲醇含5 mmol·L-1醋酸铵,流速:0. 60 m L·min-1,梯度洗脱,柱温:40℃,进样量:10. 0μL,正负离子分段同时采集,多反应监测(MRM)扫描分析,考察该方法的专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。结果奥氮平和舍曲林在1~500 ng·m L-1内、利培酮和米氮平在0. 2~100. 0 ng·mL-1内、阿立哌唑在0. 5~250. 0 ng·mL-1内,线性相关系数均大于0. 99;日内、日间精密度(RSD)均小于15%,提取回收率为90. 0%~98. 3%,方法准确度为85. 2%~112%。结论本方法操作简便快速、准确度高、特异性强和灵敏度好,可用于同时进行5种精神类药物的血药浓度监测。

Objective To establish a HPLC-tandem mass-mass spectrometry(HPLC-MS/MS)method to simultaneously determine the concentration of five psychiatric drugs(olanzapine,risperidone,aripiprazole,sertraline,mirtazapine)in human serum.Methods[2 H3]-sertraline hydrochloride was selected as internal standard and the samples were treated by protein precipitation method.The chromatographic column was Kinetex?C18 LC Column(50 mm×3.0 mm,2.6μm),mobile phase was 5 mmol·L-1 ammonium acetate-methanol contained with 5 mmol·L-1 ammonium acetate,flow rate was 0.60 mL·min-1,column temperature was 40℃,injection volume was 10.0μL,the protonated ions of analytes were detected in positive ionization in multiple reaction monitoring mode(MRM).The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were investigated.Results The linear ranges of olanzapine and sertraline were in 1-500 ng·m L-1,risperidone and mirtazapine were in 0.2-100.0 ng·mL-1 and aripiprazole was in 0.5-250.0 ng·m L-1,the linear dependent coefficient were all greater than 0.99.The intraday and interday relative standard deviation(RSD)were all less than 15%.The recovery rate of extraction was 90.0%-98.3%and the method accuracy was 85.2%-112%.Conclusion The method is simple,rapid,accurate,specific,sensitive,and suitable for the determination of psychiatric drugs in human serum.