LC-MS/MS法测定健康人血浆中坦洛新的浓度  

Determination of Tamsulosin in Plasma by LC-MS/MS

作　　者：梁彬彬[1] 王艳凯 胡玉钦[2] 刘建芳 

机构地区：[1]河北医科大学研究生院,河北石家庄050017 [2]白求恩国际和平医院药剂科,河北石家庄050082

出　　处：《解放军药学学报》2017年第4期311-314,共4页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：基金项目:军队特需药品临床评价技术平台研究;No.2011ZXJ09202-012

摘　　要：目的建立快速、灵敏的LC-MS/MS方法测定健康人血浆中坦洛新的浓度,并应用于盐酸坦洛新缓释制剂的药代动力学研究。方法血浆样品用甲基叔丁基醚提取浓缩后进行LC-MS/MS分析。分离柱为Zorbax SB-C18(100 mm×2.1mm,3.5μm),流动相为10mmol·L-1乙酸铵(含0.2%冰乙酸)-甲醇(52∶48,V/V),流速:0.30ml·min-1;用Qtrap 4500型质谱仪检测,APCI离子源,正离子多反应监测,监测离子对为m/z 409.1→m/z 228.1(坦洛新)和m/z 412.1→m/z 231.1(氘代坦洛新,内标)。结果血浆中坦洛新的线性范围为0.05~50ng·ml-1,最低定量限为0.05ng·ml-1,提取回收率为84.8%~95.8%,定量下限和低、中、高3个浓度质控样品的日内和日间RSD均低于8.1%。血浆样品在室温6h、3次冻融循环及-20℃冻存23d后,测定浓度的相对偏差均在±15%以内。结论本法灵敏、准确、稳定,可用于人血浆中盐酸坦洛新浓度的测定及药代动力学研究。Objective To develop a quick and sensitive LC-MS/MS method for the determination of tamsulosin in human plasma, and adopt this method in pharmacokinetic studies of tamsulosin hydrochloride sustained-release preparations. Methods The plasma samples were extracted with methyl tert-butyl ether and the concentrated solution was analyzed by LC-MS/MS method.The separation was conducted on a Zor- bax SB-C18 column（100 mm×2.1 mm,3.5μm） with a mobile phase consisting of 10 mmol .L-1 ammonium acetate（0.2 formic acid）-methanol（52 48, V/V ） at a flow rate of 0.30 ml .min-l.The detection was completed by Qtrap 4500 mass spectrometry equipped with APCI source in a positive ion and multiple reac- tion monitoring （MRM） mode. The monitoring ions were m/z 409.1---228.1 for tamsulosin and m/z 412.1--231.1 for d3-tamsulosin（internal standard）. Results The plasma standard curve was linear in the range of 0.05--50 ng .ml- and LLOQ was 0.05 ng .ml-.The plasma extraction recovery of tamsulosin was 84.80/oo--95.80//oo. The intra-day and inter-day RSD of LLOQ samples and those of QC samples were less than 8.1 %.The relative error of the determined concentration was within 4-15 when the plasma samples were placed at room temperature for 6 h after three freeze-thaw cycles or -20℃ for 23 d.Conclusion This method has been proved to be sensitive,accurate and precise.h can be applied to the pharmacokinetic study of tamsulosin preparations.

关 键 词：盐酸坦洛新 LC-MS/MS 药代动力学 血药浓度 

分 类 号：R969.1[医药卫生—药理学]