中国临床药学杂志

目的建立LC-MS/MS法同时测定人血浆中西酞普兰、米氮平、舍曲林和度洛西汀浓度。方法血浆样品用乙腈沉淀蛋白后,以替米沙坦为内标,选用Agilent Eclipse Plus-C₁₈(100 mm×2.1 mm,3.5μm)色谱柱,以乙腈-10 mmol·L^-1醋酸铵溶液(均含0.1%甲酸)为流动相梯度洗脱,梯度流速恒定为0.25 mL·min^-1,柱温为30℃,进样量10μL,总分析时间为5 min,采用电喷雾离子化源,正离子方式,多反应监测(MRM)扫描方式进行监测。结果血浆中西酞普兰和米氮平的线性范围为0.50~100μg·L^-1(r>0.99),定量下限为0.50μg·L^-1;舍曲林和度洛西汀的线性范围为0.20~50μg·L^-1(r>0.99),定量下限为0.20μg·L^-1;方法回收率91.6%~109.2%;日内、日间RSD均<15%;提取回收率77.6%~92.6%,无明显基质效应。结论该方法快速、灵敏、准确,专属性强,重复性好,适用于临床测定血药浓度及药动学研究。

AIM To establish an LC-MS/MS method for simultaneous determination of citalopram,mirtazapine,sertraline and duloxetine in human plasma.METHODS The plasma samples were precipitated by acetonitrile,with telmisartan as an internal standard.The separation was achieved on Agilent Eclipse Plus-C₁₈ column(100 mm × 2.1mm,3.5 μm)and eluted with linear gradient using acetonitrile and 10 mmol·L^-1 ammonium acetate,both of which were acidified with 0.1%formic acid at the flow rate of 0.25 mL· min^-1,the injection volume was 10 μL and the column temperature was 30℃.The total time of the analysis was 5 min.Detection of the analytes were achieved using positive ion electrospray ionization(ESI) in the multiple reaction monitoring(MRM) mode.RESULTS The linear calibration curves of citalopram and mirtazapine were obtained in the concentration range of 0.50-100 μg· L^-1(r > 0.99),with the lower limit of quantitation(LLOQ) of 0.50 μg· L^-1.While the standard curves of sertraline and duloxetine were linear in the concentration range of 0.20-50 μg· L^-1(r > 0.99) with the LLOQ of 0.20 μg· L^-1.The average accuracy was between91.6%-109.2%.Intra-day and inter-day relative standard deviations were both below 15%.The recoveries of low,middle and high concentrations were 77.6%-92.6%,and no significant matrix effect was exhibited.CONCLUSION The established method is rapid,sensitive,accurate and specific repeatable,and can be used for the determination of plasma concentration and pharmacokinetic study.