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本研究建立了一个新的、灵敏的液相色谱-串联质谱法用于测定大鼠血浆中SM-1的浓度.在简单的蛋白沉淀处理后,用乙腈-甲醇-10mM乙酸铵溶液(37.5∶37.5∶25,v/v/v)作为流动相,在C18反相色谱柱(50 mm×4.6 mm,3.5 μm)上分离SM-1和内标(吉非替尼).质谱检测使用三重四级杆串联质谱,电喷雾正离子模式、质谱多反应监测技术对待测物SM-1和内标物分别在质核比为407.3→203.4和447.3→128.3处进行检测.方法学验证的线性范围为30至6000 ng/mL,批内和批间的精密度都小于4.7％.平均回收率在98.7％-104.1％之间.在样品制备和分析程序中SM-1都是稳定的.测定结果均符合FDA生物分析方法指导原则的要求.该方法已成功地应用于测定单次口服50、100、200 mg/kg剂量后,大鼠血浆中SM-1的浓度.“,”A new and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of SM-1 in rat plasma.After a simple protein precipitation,SM-1 and internal standard (gefitinib) were separated with gradient elution on a Waters XBridge C18 (50 mm×4.6 mm,3.5 μm) using acetonitrile-methanol-10 mM ammonium acetate (37.5∶37.5∶25,v/v/v) as mobile phase.The triple quadruple mass spectrometer was set in positive electrospray ionization mode,multiple reaction monitoring was used for quantification.The precursors to produce ion transitions monitored for SM-1 and IS were m/z 407.3→203.4 and 447.3→128.3,respectively.The method validation was conducted over the curve range of 30-6000 ng/mL.The intra-and inter-day precisions were less than 4.7％,the average extraction recoveries ranged from 98.7％ to 104.1％ for each analyte.SM-1 was proved to be stable during sample storage preparation and analytical procedures.All the results met the acceptance criteria in accordance with the FDA guidance for bioanalytical method.Consequently,this method was successfully applied to determine SM-1 concentrations in rats after oral administrations at the doses of 200,100 and even 50 mg/kg.