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 Zorbax SB-C18 column(100 mm × 2.1 mm,3.5 μm) 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-1.The detection was completed by Qtrap 4500 mass spectrometry equipped with APCI source in a positive ion and multiple reaction 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-1 and LLOQ was 0.05 ng ·ml-1.The plasma extraction recovery of tamsulosin was 84.8％-95.8％.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 ±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.It can be applied to the pharmacokinetic study of tamsulosin preparations.%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×2.1 mm,3.5 μm),流动相为10 mmol·L-1乙酸铵(含0.2％冰乙酸)-甲醇(52∶48,V/V),流速:0.30 ml·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0.05～50 ng·m1-1,最低定量限为0.05 ng ·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23 d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.
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