大鼠血浆中阿霉素HPLC-MS/MS测定法及其在药动学中的应用Determination of adriamycin in rats
陈思明,金艺,乔明曦,徐海燕,吴瑞阳,袁波
CHEN Si-ming,JIN Yi,QIAO Ming-xi,XU Hai-yan,WU Rui-yang,YUAN Bo(School of Pharmacy
摘要(Abstract):
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。
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.
关键词(KeyWords):
阿霉素;液相色谱-串联质谱法(LC-MS/MS);大鼠;血浆
adriamycin;liquid chromatography-tandem mass spectrometry(LC-MS/MS);rat;plasma
基金项目(Foundation): 国家自然科学基金资助项目(30801456)
作者(Author):
陈思明,金艺,乔明曦,徐海燕,吴瑞阳,袁波
CHEN Si-ming,JIN Yi,QIAO Ming-xi,XU Hai-yan,WU Rui-yang,YUAN Bo(School of Pharmacy
DOI: 10.14066/j.cnki.cn21-1349/r.2012.03.015
参考文献(References):
- [1]熊雯,蒋心惠,张丹.盐酸阿霉素脂质体与盐酸阿霉素在大鼠体内的组织分布[J].中国医院药学杂志,2010,30(5):379-382.
- [2]CARTER S K.Adriamycin-A review[J].J Natl CancerInst,1975,55(6):1265-1274.
- [3]LENAZ L,PAGE JA.Cardiotoxicity of adriamycin andrelated anthracyclines[J].Cancer Treat Rev,1976,3(3):111-120.
- [4]CHAN K K,WONG C D.Quantitative thin-layer chro-matography:Thin-film fluorescence scanning analysis ofadriamycin and metabolites in tissue[J].ChromatogrB,1979,172:343-349.
- [5]王杰民,傅江平,赵刚,等.荧光光谱法测定家兔血浆中阿霉素浓度[J].上海第一医学院学报,1984,11(3):169-173.
- [6]PIALL E,AHERNE G W,MARKES V.Evaluation of acommercially available radioimmunoassay part formeasurement of doxorubicin in plasma[J].Clin Chem,1982,28(1):119-121.
- [7]LAUBROCK N,HEMPEL G,WESTHOFF P,et al.Thestability of doxorubicin and idarubicin in plasma andwhole blood[J].Chromatographia,2000,52(2):9-15.
- [8]EKSBORG S,STENDAHL U,LONROTH U.Compara-tive pharmacokinetic study of adriamycin and 4'epi-ad-riamycin after their simultaneous intravenous adminis-tration[J].Eur J Clin Pharmacol,1986,30(5):629-631.
- [9]MOU C,GANJU N,SRIDHAR K S,et al.Simultaneousquantitation of plasma doxorubicin and prochlorperazinecontent by high performance liquid chromatography[J].Chromatogr B,1997,703(1-2):217-224.
- [10]BUEHLERP W,ROBLESS J,ADAMIG R,et al.Analy-sis of doxorubicin in cell culture media and humanplasma using solid phase extraction and HPLC[J].Chromatographia,1999,49(3):557-562.
- [11]赵雯,张宏,卢婷利,等.RP-HPLC法测定盐酸阿霉素磁性脂质体的药物含量[J].药物分析杂志,2010,30(2):244-246.
- [12]吴燕,张福成,吴诚,等.盐酸表阿霉素长循环热敏脂质体大鼠药代动力学考察[J].药学学报,2010,45(3):365-370.
- [13]XU Ling,WANG Wei,SHENG Yu-cheng,et al.Phar-macokinetics and its correlation with tozicity of pegylat-ed-liposomal doxorubicin in chinese patients withbreast tumors[J].China Academic Journal ElectronicPublishing House,2010,35(5):593-601.
- [14]钟大放.以加权最小二乘法建立生物分析标准曲线的若干问题[J].药物分析杂志,1996,16(5):343-346.
- [15]祝春来,张邦乐,宦梦蕾,等.液相色谱-串联质谱法同时测定大鼠血浆中阿霉素和塞来昔布[J].现代生物医学进展,2009,9(22):4222-4225.
- [16]龚连生,曾雅娟,张阳德,等.阿霉素纳米脂质体大鼠体内的药动学研究[J].中国现代医学杂志,2010,20(1):9-12.
- 阿霉素
- 液相色谱-串联质谱法(LC-MS/MS)
- 大鼠
- 血浆
adriamycin - liquid chromatography-tandem mass spectrometry(LC-MS/MS)
- rat
- plasma