摘要
目的建立高效液相色谱-串联质谱（LC-MS/MS）方法测定人尿样中氯法拉滨的浓度。方法采用AB SCIEX QTRAP 5500串联质谱仪及Agilent1200高效液相色谱仪进行检测。尿样经甲基叔丁基醚提取处理,以克拉屈滨为内标。色谱柱为ThermoC18柱（150mm×4.6mm,5μm）,流动相为乙腈—4mM乙酸铵（含0.3%的甲酸）（250∶3,v/v）;流速为0.5mL·min-1。氯法拉滨和克拉屈滨的MRM扫描离子通道m/z分别为304.2→170.0,286.1→170.0。进样量：10μL。结果氯法拉滨和克拉屈滨分离良好,保留时间分别为3.77min,3.88min。氯法拉滨在2.5~500ng·mL-1范围内线性关系良好（r=0.9995）,日内、日间RSD均低于6.39%,准确度（RE）均低于10.17%。结论本法样品预处理简便快捷,检测结果专属性强,灵敏度好,准确度高,适用于氯法拉滨药代动力学的研究。
Objective To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the determination of clofarabine in human urine. Method The drug was determinated by LC-MS/ MS using electrospray ionization. The urine samples were extracted with methyl tert-butyl ether, and cladribine is the internal standard （IS）. The analytical column was a Thermo C18 column （150 mm×4.6 mm,5μm）. The mobile phase, acetonitrile-4 mM ammonium acetate （contains formic acid ）（250：3, v/v）, was used at a flow rate of 0.5 mL·min-1 . Clofarabine and cladribine were detected on multiple reaction monitoring （MRM） by the transitions from the precursor to the product ion （m/z 304.2/170.0 and m/z 286.1/170.0）. The injection volume was 10μL. Results Calibration curve had good linearity in the range of 2.5 ~500 ng·mL-1 （r=0.9995）. The intrabatch and inter-batch precision （RSD） were all less than 6.39% and the relative errors were all less than 10.17%. Conclusion The separation of Cladribine and Clofarabine was good. The retention time of these analytes were 3.77 min and 3.88 min. The established LC-MS/MS method is shown to be sensitive, accurate and simple for determination of clofarabine in human urine. It is suitable for the pharmacokinetics of clofarabine.
出处
《肿瘤药学》
CAS
2011年第2期140-143,156,共5页
Anti-Tumor Pharmacy
