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目的建立同时测定人血浆中9种抗抑郁类药物浓度的超高效液相色谱-质谱联用法(UPLC-MS/MS)。方法以奥沙西泮为内标,血浆经乙腈直接沉淀后进行分析。色谱柱:Acquity UPLC HSS C18柱(2.1 mm×150 mm,1.8μm);流动相:含0.01%甲酸水溶液-含0.01%甲酸甲醇溶液,梯度洗脱,流速:0.3 mL·min-1,进样量:3μL。用电喷雾离子源,多离子反应监测,正离子扫描进行测定。考察该方法的专属性、标准曲线和定量下限、精密度与回收率、基质效应和稳定性。结果西酞普兰、文拉法辛、米安色林、帕罗西汀、氟伏沙明、氟西汀、丙咪嗪、马普替林和舍曲林血药浓度分别在2.50~1003.00(r=0.999 0),2.50~1003.00(r=0.998 8),2.50~1003.00(r=0.998 9),2.50~1005.00(r=0.998 4),2.50~1003.00(r=0.998 8),2.50~1003.00(r=0.998 6),2.50~1000.00(r=0.998 8),2.52~1007.00(r=0.996 8),2.52~1007.00 ng·mL~(-1)(r=0.998 7)内线性关系良好;最低定量下限分别为0.62,0.06,0.62,0.25,0.62,0.62,0.62,0.25,0.06 ng·mL~(-1);日内、日间精密度(RSD)均<15%;提取回收率均>75%。结论本方法操作简便、专属性强、灵敏度高,可用于血药浓度的临床监测以及药代动力学研究。
Objective To establish a simultaneous determination of nine antidepressants in human plasma by ultra performance liquid chromatography-mass spectrometry (UPLC-MS / MS). Methods Osazepam was used as an internal standard and plasma was directly precipitated by acetonitrile. Column: Acquity UPLC HSS C18 column (2.1 mm × 150 mm, 1.8 μm); mobile phase: 0.01% formic acid in water with 0.01% formic acid in methanol and gradient elution at a flow rate of 0.3 mL · min -1 Amount: 3 μL. Electrospray ionization, multi-ion reaction monitoring, positive ion scan were performed. The specificity, standard curve and limit of quantification, precision and recovery, matrix effect and stability of this method were examined. Results The plasma concentrations of citalopram, venlafaxine, mianserin, paroxetine, fluvoxamine, fluoxetine, imipramine, maprotiline and sertraline were between 2.50 and 1003.00 (r = 0.998 4), 2.50-1003.00 (r = 0.998 8), 2.50-1003.00 (r = 0.998 8), 2.50-1003.00 (r = 0.998 9), 2.50-1005.00 (r = 0.998 6), 2.50-1000.00 (r = 0.998 8), 2.52-1007.00 (r = 0.996 8) and 2.52-1007.00 ng · mL -1 (r = 0.998 7) respectively. The lowest limit of quantitation (0.62,0.06,0.62,0.25,0.62,0.62,0.62,0.25,0.06 ng · mL -1). The intra-day and inter-day precision (RSD) were all less than 15% and the recovery rates were both 75%. Conclusion The method is simple, specific, sensitive and can be used for the clinical monitoring of plasma concentration and pharmacokinetic studies.