LC-MS/MS法测定大鼠脑微透析液中7-乙基-10-羟基喜树碱的浓度  

Determination of 7-ethyl-10-hydroxycamptothecin in microdialysates from rat brain with LC-MS/MS

作　　者：曹阳[1] 程巧鸳[2] 卢红阳[3] 张恒义[4] 

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]浙江省食品药品检验所,浙江杭州310004 [3]浙江省肿瘤医院肿瘤内科,浙江杭州310022 [4]浙江大学生物医学工程与仪器科学学院,浙江杭州310027

出　　处：《浙江大学学报（医学版）》2013年第1期98-102,共5页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省自然科学基金(No.Y2110004);浙江省中医药科技计划项目(NO.2010ZA006);浙江省医药卫生科技计划项目(No.2010KYA035)

摘　　要：目的:建立一种能够测定大鼠脑微透析液中7-乙基-10-羟基喜树碱(7-Ethyl-10-Hydroxycamptothecin,SN-38)浓度的分析方法。方法:采用LC-MS/MS法,色谱柱为Agilent EclipsePlus C18反相柱(2.1 mm×100 mm,1.8μm);流动相为乙腈-0.1%甲酸,梯度洗脱;流速为0.3 ml/min;柱温为35℃。采用电喷雾离子化,多反应监测(multiple reaction monitoring,MRM)测定大鼠脑微透析液中SN-38(m/z 393.1→349.1)的浓度。结果:空白透析液无干扰;SN-38在0.1015～1015 ng/ml范围内线性关系良好(r=0.9995),定量下限为0.1015 ng/ml;回收率为97.54%～100.60%;精密度和稳定性均良好;脑微透析液中SN-38的浓度呈明显药动学过程,给药220 min后达到顶峰。结论:本实验所建立的LC-MS/MS分析方法专属性强、灵敏度高,可用于分析大鼠脑微透析液中SN-38的浓度。Objective： To establish a method for determination of 7-ethyl-10-hydroxycamptothecin （SN-38） in microdialysates from rat brain. Methods： The concentrations of SN-38 were measured by LC-MS/MS method with Agilent Eclipse Plus Cls （2.1 mmx 100 mm, 1.8 μm）reversed phase column using acetonitrile-0.1% methanoic acid as mobile phase with gradient elution at a flow rate of 0.3 ml/ min and temperature at 35℃. Multiple reaction monitoring using the precursor to product ion combinations of rn/z 393.1±349.1 was performed to detect SN-38 in microdialysates from tat brain. Results： Blank microdialysate had non-interference. The method was linear over the concentration range of O. 1015 - 1015 ng/ml （r = 0. 9995 ） ; and the lower limit of quantification （LOQ） was 0. 1015 ng/ml. The recovery of assay for SN-38 ranged from 97.54% - 100.60%. The intra- and inter-day precision and stability were both well. The concentrations of SN-38 in brain microdialysates presented pharmacokinetics process and achieved the peak after 220 min. Conclusions： The fully validated LC-MS/MS analytical method has high specificity and sensibility, which can be used effectively to analyze SN-38 in microdialysates from rat brain.

关 键 词：微透析 脑/药物作用 喜树碱/药理学 色谱法 高压液相 串联质谱法 

分 类 号：R96[医药卫生—药理学]