液相色谱-质谱联用法测定人血浆中卢比替康的浓度  

Determination of rubitecan in human plasma by liquid chromatography-mass spectrometry method

作　　者：陈磊[1] 杨劲[1] 于锋[2] 王广基[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室 [2]中国药科大学药理研究室

出　　处：《中国临床药学杂志》2007年第5期283-287,共5页Chinese Journal of Clinical Pharmacy

基　　金：国家高技术研究发展计划(863计划)课题(编号:2003AA223471;2005AA223C70)项目

摘　　要：目的建立液相-质谱(LC-MS)联用方法,用于抗肿瘤药卢比替康在肿瘤患者血浆中的定量分析。方法血浆样品用0.2 mL盐酸(0.5 mol·L^(-1))酸化后,乙酸乙酯提取,上清液在40℃水浴条件下氮气流吹干,萃取物用流动相复溶后进LC-MS联用仪分析测定。采用反相C_(18)柱进行色谱分离,流动相为:乙腈:10 mmol·L^(-1)醋酸铵水溶液(90:10,V/V)。结果本方法在5～500μg·L^(-1)内线性良好,r=0.999 4(n=4),低、中、高3种浓度质控样品的批内及批间RSD均<5%,提取回收率分别为80.66%、88.47%、85.05%,最低定量限5μg·L^(-1)。结论本方法灵敏度高,操作简便易行,能够满足该药进行临床药动学研究的要求。AIM To develope and validate a simple and sensitive liquid chromatography-mass spectrometry （LC- MS） assay for the quantitative analysis of the investigational anticancer drug rubitecan as the lactone form in patients plasma. METHODS The analytical method involoved a acidification step with adding 0.2 mL of hydrochloric acid （0.5 mol·L^-1） to plasma sample that stabilized the pH-dependent conversion of lactone form to inactive hydroxy carboxylated form. After extraction with ethyl acetate and evaporation under gentle stream of nitrogen gas （40℃）, the dry extract was dissolved in mobile phase. The separations were performed on a RP-C18 column, using a mixture of acetonitril- 10mmol·L^-1-ammonium acetate （90： 10, V/V） and MS detection. RESULT The presented assay was linear over a concentration range of 5 - 500 μg·L^-1（ r = 0. 999 4）with lower limit of quantiation of 5 μg·L^-1.Inter-day and intra-day precisions were always less than 5% in the concentration range of interest. The extraction recovery were 80.66%, 88.47 % and 85.05 %, respectively. CONCLUSION The reported assay method shows good characteristics of linearity, sensitivity, selectivity and precision allowing applying in pharmacokinetic studies.

关 键 词：卢比替康 液相色谱-质谱法 药动学 

分 类 号：R96[医药卫生—药理学]