摘要
目的建立高效液相色谱-串联质谱法(LC-MS/MS)测定人血浆中氯法拉滨浓度。方法采用API3000串联质谱仪及Shimadzu系列液相色谱仪进行检测。血浆样品经乙酸乙酯提取处理,以克拉屈滨为内标。色谱柱为ThermoC18柱(4.6mm×150mm,5μm),流动相为乙腈-水(250∶3,其中含4mmol的乙酸铵和0.3%的甲酸),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304.0→170.0,286.1→170.0。进样体积为20μL,每个样品的分析时间为5min。结果氯法拉滨和克拉屈滨保留时间分别为4.00,4.11min。氯法拉滨在10～2000ng·mL-1内线性关系良好(r=0.9995),日内、日间RSD均低于9.60%,准确度为101.10%～102.94%。结论本法样品预处理简便快速,检测准确、灵敏、专一,适用于氯法拉滨药动学的研究。
OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the determination of clofarabine in human plasma. METHODS The drug was determinated by LC-MS/MS using electrospray ionization. The plasma samples were extracted with ethyl acetate. Cladribine was the internal standard （IS）. The analytical column was Thermo C18 column （4.6 mm×150 mm,5 μm）. The mobile phase consisted of acetonitrile-water （250：3,Which contains 4 mmol of ammonium acetate and 0.3% formic acid） 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 304.0/170.0 and m/z 286.1/170.0）. The injection volume was 20 μL and the total run time was 5.0 min. RESULTS Calibration curve showed good linearity in the range of 10-2 000 ng·mL-1 （r=0.999 5）. The intra-batch and inter-batch precisions （RSD） were all less than 9.60% and the accuracy was within 101.10%-102.94%. CONCLUSION The retention time of cladribine and clofarabine were 4.00 and 4.11 min. The established LC-MS/MS method is sensitive,accurate and simple for the determination of clofarabine in human plasma. It is suitable for the pharmacokinetics of clofarabine.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第19期1496-1499,共4页
Chinese Pharmaceutical Journal
