大鼠血浆中阿霉素HPLC-MS/MS测定法及其在药动学中的应用

目的建立大鼠血浆中阿霉素浓度的液相色谱-串联质谱(LC-MS/MS)测定方法。方法色谱柱:Venusil ASB C18(150 mm×4.6 mm,5μm),流动相:乙腈-5 mmol.L-1乙酸铵-甲酸(体积比为35.0∶65.0∶0.5),采用沉淀蛋白法,以多反应监测(multiple reaction monitoring,MRM)扫描方式检测,测定大鼠尾静脉注射阿霉素纳米胶束溶液后血浆中药物浓度。结果血浆中阿霉素质量浓度在1～1 000μg.L-1内线性关系良好,r=0.996 0;日内和日间精密度RSD≤13.2%;阿霉素的平均提取回收率为89.7%～95.7%;阿霉素在大鼠血浆中主要药动学参数为t1/2(30.5±5.2)h,ρmax(954.3±80.6)μg.L-1,AUC0-∞/(290.2±40.4)μg.h.L-1。结论该方法适用于阿霉素在大鼠体内药动学的研究。

Determination of adriamycin in rats

Objective To develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the determination of adriamycin and use the mathod to quantify adriamycin in rat plasma.Methods The plasma samples were deproteinated with acetonitrile,and separation was performed on a reversed-phase Venusil ASB C18 column(150 mm×4.6 mm,5 μm).The mobile phase contained acetonitrile-5 mmol · L-1 ammonium acetate-formic acid(V∶ V∶ V=35.0∶ 65.0∶ 0.5).Detection was carried out by multiple reaction monitoring.Adriamycin nanometer micelle was used in rats by inject caudal vein.Results The method has a linear calibration curve over the range of 1-1 000 μg · L-1(r=0.996 0).The intra-day and inter-day accuracy and precision were within 13.2% for the analyte.The average recoveries were between 89.7%-95.7%.Main pharmacokinetic parameters were as follows:t1/2(30.5±5.2)h,ρmax(954.3±80.6) μg · L-1,AUC0-∞/(290.2±40.4) μg · h · L-1,respectively.Conclusions It is a rapid,sensitive,and specific analytic method.The proposed method can be appied for the identification and quantification in pharmacokinetic studies of adriamycin in rat plasma.