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目的建立一种同时检测人血浆中格列美脲、氟西汀及其代谢物羟基格列美脲、去甲氟西汀浓度的超高液相色谱-质谱的方法。方法以咪达唑仑为内标,血浆样品用乙腈沉淀后检测。用Acquity UPLC BEH C18柱为分离柱,流动相:乙腈-0.1%甲酸,梯度洗脱,流速:0.45 m L·min-1,柱温:40℃;用Acquity Xevo TQD三重四级杆质谱仪(电喷雾离子源)质谱检测,用多反应监测法测定样品中的药物浓度。考察该方法的专属性、标准曲线和定量下限、精密度和回收率、基质效应及稳定性。结果格列美脲、羟基格列美脲、氟西汀和羟基氟西汀的标准曲线分别为y=1.49×10-2x+4.23×10-2(r=0.999 7),y=0.97×10-2x-0.26×10-2(r=0.999 5),y=1.72×10-2x+9.48×10-2(r=0.999 3),y=8.66×10-2x-1.05×10-2(r=0.999 4),分别在5~1000,2.5~500,1~200,0.5~100 ng·m L-1线性关系良好。药物及其代谢物的回收率均大于90%,日内、日间精密度均小于15%。结论该方法简便、快速,可用于人血浆格列美脲、氟西汀及其代谢产物的检测、药代动力学研究和药物相互作用研究。
OBJECTIVE To establish a method for simultaneous determination of glomeruline, fluoxetine and their metabolites hydroxyglmeline and nifacil in human plasma by ultra performance liquid chromatography-mass spectrometry. Methods Midazolam was used as an internal standard, and plasma samples were detected by acetonitrile precipitation. Using an Acquity UPLC BEH C18 column with a mobile phase of acetonitrile-0.1% formic acid, gradient elution at a flow rate of 0.45 m L · min-1 at a column temperature of 40 ° C; using an Acquity Xevo TQD triple quadrupole mass spectrometer Electrospray Ionization) mass spectrometry, multi-reaction monitoring method for the determination of drug concentration in the sample. The method specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability were investigated. Results The calibration curves of glimepiride, hydroxyglmeline, fluoxetine and hydroxyfluoxetine were y = 1.49 × 10-2x + 4.23 × 10-2 (r = 0.999 7) and y = 0.97 × 10 (R = 0.999 5), y = 1.72 × 10 -2x + 9.48 × 10 -2 (r = 0.999 3), y = 8.66 × 10 -2 × -1.0 × 10 -2 (r = 0.999 4), respectively, with a good linear relationship at 5 ~ 1000, 2.5 ~ 500, 1 ~ 200 and 0.5 ~ 100 ng · m L -1, respectively. Drugs and their metabolites were greater than 90% recovery, intraday, day precision were less than 15%. Conclusion The method is simple and rapid and can be used for the determination of glimepiride, fluoxetine and its metabolites, pharmacokinetics and drug interactions in human plasma.