目的 建立超高效液相色谱串联质谱法测定人血浆中拉莫三嗪、奥氮平、喹硫平的浓度,为指导临床用药提供帮助。方法 血浆样品经甲醇沉淀蛋白后进样分析,以伏立康唑为内标,采用 ACQUITY UPLC BEH C18(2.1 mm×50 mm, 1.7 μm)分离;以含0.1%甲酸的水溶液-甲醇溶液为流动相,梯度洗脱。电喷雾电离源正离子检测模式,以多反应监测(multiple reaction monitoring,MRM)方式进行分析。结果 测定人血浆中拉莫三嗪、奥氮平、喹硫平分别在0.5~20 μg·mL-1、2~200、10~1 000 ng·mL-1内线性良好。基质效应、提取回收率、准确度、精密度和稳定性均符合要求,该法成功用于45例临床患者血浆样本分析。结论 该方法操作简单快速,灵敏度高,专属性高且稳定,测定结果可靠,适用于人血浆中拉莫三嗪、奥氮平、喹硫平的分析,能够服务于临床治疗药物监测。
Abstract
OBJECTIVE To establish a highly sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of the concentrations of lamotrigine, olanzapine and quetiapine in human plasma to provide guidance for clinical drug use. METHODS The plasma samples were precipitated by methanol, voriconazole was used as internal standard, and then gradiently eluted by ACQUITY UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm) using mobile phase consisting of 0.1% formic acid solution and methanol. Multiple reaction monitoring (MRM) was conducted in ion detection mode using positive electrospray ionization source. RESULTS The linear ranges of the calibration curves for lamotrigine, olanzapine and quetiapine in human plasma were 0.5-20 μg·mL-1, 2-200 and 10-1 000 ng·mL-1, respectively. The method had good matrix effect, extraction recovery, accuracy, precision and stability, and was successfully applied to analyze plasma samples of 45 patients. CONCLUSION The UPLC-MS/MS method for determination of lamotrigine, olanzapine and quetiapine is proven to be a sensitive and reliable protocol for clinical therapeutic drug monitoring.
关键词
拉莫三嗪 /
奥氮平 /
喹硫平 /
超高效液相色谱-串联质谱法 /
治疗药物监测
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Key words
lamotrigine /
olanzapine /
quetiapine /
ultra-performance liquid chromatography-tandem mass spectrometry /
therapeutic drug monitoring
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中图分类号：
R969
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参考文献
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脚注
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基金
国家青年基金资助项目(81903700);江省药学会资助项目(2018ZYY03)
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