论文部分内容阅读
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–10 mM乙酸铵溶液(37.5:37.5:25,v/v/v)作为流动相,在C_(18)反相色谱柱(50 mm×4.6 mm,3.5μm)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/m L,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。
This study established a new, sensitive liquid chromatography-tandem mass spectrometry method for the determination of plasma concentrations of SM-1 in rats. After a simple protein precipitation treatment, the column was eluted with acetonitrile-methanol-10 mM ammonium acetate solution (37.5: 37.5: 25, v / v / v) as the mobile phase on a C 18 reverse phase column (50 mm × 4.6 mm , 3.5 [mu] m), SM-1 and internal standard (gefitinib). Mass Spectrometry Detection The SM-1 and the internal standard of the analyte SM-1 and the internal standard were detected at the mass-to-nucleus ratios of 407.3 → 203.4 and 447.3 → 128.3 respectively using triple quadrupole tandem mass spectrometry, electrospray positive ion mode and mass spectrometry multiple reaction monitoring. The linear range of methodological validation was 30 to 6000 ng / mL, and the intra- and inter-batch precision was less than 4.7%. The average recovery was between 98.7% and 104.1%. SM-1 is stable in sample preparation and analysis procedures. The results are in line with FDA guidelines for bioanalytical methods. This method has been successfully applied to determine the concentration of SM-1 in rat plasma after a single oral dose of 50, 100, 200 mg / kg.