论文部分内容阅读
建立一种快速、灵敏的液相色谱-串联质谱法(LC-MS/MS)测定大鼠血浆中微量的盐酸表阿霉素(EPI)浓度的方法。以盐酸柔红霉素为内标,血浆样品用甲醇沉淀蛋白后进样,采用CAPCELLPAKC18色谱柱(3.0mm×50mm,3μm),甲醇-0.1%甲酸水溶液(80∶20)为流动相,以HP1200-6410QQQLC/MS型质谱仪多重监测(MRM)扫描方式检测。大鼠尾静脉注射等剂量(12mg·kg-1)的EPI溶液、普通脂质体(EPI-LIP)及长循环热敏脂质体(EPI-LTSL),采用DASver2.0软件拟合分析并求算各组药动学参数。结果血浆中EPI的线性范围为:0.01~50μg·mL-1,定量下限为0.01μg·mL1;批内和批间精密度均小于11.9%;平均萃取回收率分别为89.3%和92.1%;3组药物在大鼠体内药代动力学行为均符合三室模型,EPI-LTSL组的t1/2α、t1/2β、t1/2γ、AUC0-∞、MRT0-∞分别是EPI溶液组及EPI-LIP组的7.5、1.3、12.6、12.9、3.7倍及1.6、1.4、12.3、2.9、2.6倍,而后两组的平均清除率(CL)约为EPI-LTSL组的13.4倍。EPI-LTSL能显著提高AUC并延长药物在大鼠体内的循环时间。
A rapid and sensitive LC-MS / MS method for the determination of epirubicin hydrochloride (EPI) in rat plasma was established. To daunorubicin hydrochloride as an internal standard, the plasma samples were precipitated with methanol and then injected into the sample. CAPCELLPAKC18 column (3.0 mm × 50 mm, 3 μm) and methanol-0.1% formic acid aqueous solution (80:20) -6410QQQLC / MS mass spectrometer multiple monitoring (MRM) scan detection. The tail vein of rats were injected EPI solution (EPI-LIP) and EPI-LTSL at the same dose (12 mg · kg -1) Calculate the pharmacokinetic parameters of each group. Results The linear range of EPI in plasma was 0.01-50μg · mL-1 with a lower limit of quantitation of 0.01μg · mL1. The intra- and inter-assay precision was less than 11.9%. The average extraction recoveries were 89.3% and 92.1%, respectively. 3 The pharmacokinetics of the two drugs in rats were in accordance with the three-compartment model. The t1 / 2α, t1 / 2β, t1 / 2γ, AUC0-∞ and MRT0-∞ in EPI-LTSL group were respectively EPI solution group and EPI-LIP group 12.6, 12.9, 3.7 times and 1.6, 1.4, 12.3, 2.9, 2.6 times, respectively, while the average clearance (CL) of the latter two groups was about 13.4 times that of the EPI-LTSL group. EPI-LTSL significantly increased AUC and prolonged drug circulation in rats.