摘要
目的:为临床研究坦索罗辛人体药物代谢动力学建市一种特异、灵敏、快速、重现性好的同相萃取(SPE)联合 LC-MS/MS 定晶分析方法。方法:使用200 μL含待测药物的血浆,加入内标 AB289和稀释液混匀,使用 MCX 96 well 的 SPE 柱进行自动化样品前处理。HPLC 色谱柱为 XTerra RP18(2.1mm×50 mm,3.5 μm);流动相为甲醇-乙腈-10 mmol·L^(-1)醋酸铵(pH5.0)(50:20:30);进样毋10 μL;室温下测定。质谱榆测方式为 ESI^+,MRM 扫描,监测坦索罗辛 m/z 409.2→228.2,内标 m/z423.2→285.1。分析时间2.2 min。结果:在0.10～25.00ng·mL^(-1)的范围内本法线性良好(r>0.999),最低定量限为0.10ng·mL^(-1),以 RSD 表示的日内与日间精密度<5%,以相对偏差 RE 表示的准确度<±10%,萃取回收率在89.2%～87.4%(n=5)。所有稳定性考察项目结果均符合要求。结论:本法在国内首次尝试将自动化的 SPE 样品处理技术引入批量的坦索罗辛血浆样品前处理中,建立了一种可以适用于临床试验分析需求的生物样品定最方法。
Objective ： To offer a specific, sensitive, efficient and robust method using combined SPE and LC - MS/MS techniques for the quantitative determination of tamsulosin in human plasma. Method： After mixed with IS（ AB289 ） and water dilutes, 200 μL of plasma containing the test drug was applied on 96 - well plate of MCX columns to complete the solid phase extraction （ SPE ） procedure automatically. On HPLC, a reversed - phase analytical column of XTerra RPI8 （2. 1 mm× 50mm, 3.5 μm） was used and the mobile phase was methanol - acetonitrile - ammonium acetate （50： 20： 30）. 10 μL of analytes was injected onto the column. Positive electrospray ionization and multiply reaction monitoring（ MRM ） mode was employed. The transition of m/z 409.2→228.2 for tamsulosin and m/z 423.2→285. 1 for the IS was monitored. Each run was 2.2 min. Results：The linear range of the calibration curve（0. 10 -25.00 ng· mL^-1）with a good correlation coefficient（ r 〉 0. 999） was obtained. The lower limit of quantification was 0. 1 ng· mL^-1 and the intra - and inter - day precisions represented by RSD were 〈 5% and accuracies represented by RE were 〈 10%. The extraction recovery rates were from 89.2% to 87.4% （ n = 5 ）. Results for all stability tests met the acceptance criteria. Conclusion：It is the first time to introduce the automated SPE system into the preparation of plasma samples with tamsulosin domestically. The results indicate that the present quantitative method is satisfied for the analysis of tamsulosin in human plasma.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2008年第5期693-697,共5页
Chinese Journal of Pharmaceutical Analysis
作者简介
通讯作者Tel：（010）65296573；E-mail：pk．frosh@gmail．com
