目的：建立LC-M S/M S测定人血浆中肌苷浓度的方法并应用于异丙肌苷药代动力学研究。方法以阿德福韦为内标，采用甲醇∶10 mmol/L 乙酸铵（15∶85，v/v ）为流动相，以Agilent SB-C18柱（5μm粒径，150．0 mm ×4．6 mm I ．D ．）为分析柱，通过电喷雾电离源（ESI），M RM扫描方式进行检测。用于定量分析的离子反应分别为m/z母离子为267．3，子离子为135．0（肌苷）和m/z母离子为272．0，子离子为134．1（阿德福韦）。结果血浆中肌苷定量的线性范围10～3000 ng/m L ，定量下限为10 ng/mL。日内、日间精密度（RSD）小于5％，平均回收率大于90％，无基质效应。结论本法专属性强，样品处理方便，灵敏度高，适用于肌苷临床药动学研究。
A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and re-extracted with dichloromethane, after which the analyte and triptorelin as an internal standard (IS) were separated on a 300SB-C18 column (150 mm 4.6 mm i.d., 5 mm particle size) using 0.1% formic acid:methanol (45:55, v/v) as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization (ESI) interface, was operated in the positive ion mode, and the multiple-reaction monitoring (MRM) transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5-249.3, respectively. The lower limit of quantification (LLOQ) was 1 ng/mL for 100 mL plasma sample and the assay was linear over the concentration range 1-1000 ng/mL. The accuracy was within a range from 0.4% to 0.5% in terms of relative error (RE) and the intra- and inter-day precisions in terms of relative standard deviation (RSD) were r2.92 and r3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin (0.5 mg/kg) to Chinese volunteers.
