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(150mm×4.6mm,5μm),流动相:乙腈-5mmol·L“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(multiplereactionmonitoring,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1~1000μg·L-1内线性关系良好,r=0.9960;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。
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,5μm). 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: tl/2 ( 30. 5 ± 5.2 ) h,max ( 954. 3 ± 80. 6 ) .g. 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 pharmacoki- netic studies of adriamycin in rat plasma.