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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 establish a rapid and sensitive LC-MS / MS method for the determination of tamsulosin in healthy human plasma and to study the pharmacokinetics of tamsulosin hydrochloride sustained-release preparation. Methods Plasma samples were extracted with methyl tert-butyl ether and concentrated for LC-MS / MS analysis. The separation column was Zorbax SB-C18 (100 mm × 2.1 mm, 3.5 μm) with a mobile phase of 10 mmol·L -1 ammonium acetate (containing 0.2% glacial acetic acid) -methanol (52:48 V / V) ml · min-1. The mass spectra of APCI ion source and positive ion were monitored by Qtrap 4500 mass spectrometer. The monitored ion pairs were m / z 409.1 → m / z 228.1 (tamsulosin) and m / z 412.1 → m / z 231.1 (deuterium tamsulosin, internal standard). Results The linear range of tamsulosin in plasma was 0.05 ~ 50ng · ml-1, the lowest limit of quantification was 0.05ng · ml-1, the recovery was 84.8% ~ 95.8%. The lower limit of quantitation and the concentrations of tamsulosin in plasma were The RSDs for both control and day samples were below 8.1%. Plasma samples at room temperature 6h, 3 freeze-thaw cycles and frozen at -20 ℃ after 23d, the relative concentrations measured were within ± 15%. Conclusion The method is sensitive, accurate and stable and can be used to determine the concentration of tamsulosin hydrochloride in human plasma and its pharmacokinetics.