液相色谱-质谱联用法同时测定大鼠血浆中柔红霉素和汉防己甲素的浓度  

Simultaneous determination of daunorubicin and tetrandrine in rat plasma by LC-MS/MS method

作　　者：刘雷[1] 王永禄[1,2] 马博[1] 朱建伟[1] 刘明[1] 吴秀娟[1] 张琪[1] 

机构地区：[1]南京工业大学药学院,江苏南京211816 [2]东南大学医学院,江苏南京210009

出　　处：《中国医院药学杂志》2015年第10期882-886,共5页Chinese Journal of Hospital Pharmacy

基　　金：江苏政府留学奖学金(2013);国家自然科学基金资助项目(编号:81170492;81373478)

摘　　要：目的：建立一种灵敏快速的LC-MS/MS方法,能够同时测定大鼠血浆中的柔红霉素（DNR）和汉防己甲素（Tet）含量。方法：色谱柱使用的是BDS HYPERSIL-C8柱（2.1 mm×100 mm,3μm）;采用乙腈-5 mmo L·L^-1醋酸铵（46∶54 V/V）作为流动相,其中含千分之四的甲酸;流速设为0.2 ml·min^-1。采用醋酸乙酯对血浆样品进行液液萃取,选择阿霉素（DOX）为内标,进行HPLC-MS/MS分析,正离子扫描,MRM模式检测。DNR、Tet和IS的定量检测离子对分别为m/z 528.4→321.3,m/z 623.1→381.8,m/z 544.4→397.6。结果：大鼠血浆中检测DNR及Tet的线性范围分别为2~500 ng·ml^-1,0.5~400 ng·ml^-1,DNR与Tet高、中、低浓度提取回收率均〉86%,日内精密度RSD〈7.3%,日间精密度RSD〈4.9%,准确度RE在-0.4%-4.5%范围内。结论：本方法可灵敏、快速地测定大鼠血浆中DNR及Tet浓度。OBJECTIVE To investigate pharmacokinetics of daunorubicin （DNR） and tetrandrine （Tet） alone or in combina- tion in healthy rats by using liquid chromatography with tandem mass spectrometry method developed and validated for quantifi- cation of DNR and Tet in rat plasma. METHODS A BDS HYPERSIL-C8 column （2. 3 mm× 75 mm, 3 μm） was used with a mobile phase consisted of acetonitrile, 5 rnmoL-L-t ammonium acetate and 0. 04% formic acid （46： 54, V/V） at a flow rate of 0. 2 ml.min 1. Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate and doxorubicin as internal stand- ard （IS）. The detection was performed using a mass spectrometer by multiple reaction monitoring （MRM） using positive ioniza- tion. The transitions monitored for DNR, Tet and IS were m/z 528→363. 1, m/z 623. 4→381.1 and m/z 544. 3→397.3, re- spectively. RESULTS Calibration curve was linear and validated over a concentration range of 2 - 500 ng. ml^-1 for DNR and 0. 5- 400 ng·ml^-1 for Tet. The inter-day precisions （RSD） were within 7. 3% and intra-day preeisions （RSD） were within 4. 9%, while the accuracy （R. E. ） values were ranged from -0. 4 % to 4. 5 % in plasma. The recoveries obtained for DNR and Tet were more than 86%. CONCLUSION LC-MS/MS method is sensitive, rapid and selective for simultaneous determination of DNR and Tet in rat plasma, and can be successfully applied to pharmacokinetic study.

关 键 词：柔红霉素(DNR) 汉防己甲素(Tet) 阿霉素(DOX) 液相色谱-质谱联用法 大鼠血浆样品检测 

分 类 号：R927.2[医药卫生—药学]