摘要
目的建立一种测定人血浆中氯法拉滨浓度的液相色谱串联质谱(LC-MS/MS)检测方法,并用于氯法拉滨的药代动力学研究.方法血浆样品经乙腈沉淀蛋白,以替米沙坦为内标.色谱柱:Aglient TC-C18柱(150.0 mm×4.6 mm,5μm),流动相:甲醇-1 mmol·L^(-1)乙酸铵溶液,梯度洗脱,流速:1.0 mL·min^(-1);柱温:35℃,进样10μL.离子喷雾离子化源,正离子模式,多重反应监测模式.考察该方法的专属性、标准曲线与定量下限、精密度与回收率、稳定性、基质效应和稀释效应.结果氯法拉滨和内标的保留时间分别为3.71和3.80 min.血浆样本中氯法拉滨在2.00~1000.00 ng·mL^(-1)内线性关系良好,标准曲线为y=3.85×10^(-3)x+1.95×10^(-3)(r=0.9949).氯法拉滨的提取回收率在80.76%以上,其日内、日间RSD在1.00%~5.69%,稳定性、基质效应和稀释效应均符合生物样本分析的相关要求.结论本方法简便、灵敏、快速、准确,适用于氯法拉滨的血药浓度测定及药代动力学研究.
Objective To develop a liquid chromatography tandem mass spectrometry(LC-MS/MS)method suitable for the determination of clofarabine in human plasma and apply it to the pharmacokinetic study of clofarabine.Methods Telmisartan was employed as the internal standard.The plasma samples were precipitated by acetonitrile.Aglient TC-C_(18)column was used for gradient elution in methanol-1 mmol·L^(-1)ammonium acetate solutionat 35℃,the flowrate was 1.0 mL·min^(-1)and the injection volume was 10μL for each sample.Electrospray ion source was applied and operated in positive multiple reaction monitoring mode.The selectivity,standard curve,precision and accuracy,extraction recoveries,stability,matrix effect and dilutive effect were investigated.Results The standard curve was y=3.85×10^(-3)x+1.95×10^(-3)and was demonstrated to be liner in the range of 2.00-1000.00 ng·mL^(-1)(r=0.9949).The average recoveries were above 80.76%.The RSDs of inter-day and intra-day were within 1.00%-5.69%.The stability,matrix effect and dilution effect all met the requirements of biological sample analysis.Conclusion The method is simple,sensitive,rapid and accurate,and it is suitable for plasma concentration determination and pharmacokinetics study of clofarabine.
作者
张茜
童卫杭
吕亚丽
陈慧
雷宁
李广润
李鹏飞
ZHANG Xi;TONG Wei-hang;Lü Ya-li;CHEN Hui;LEI Ning;LI Guang-run;LI Peng-fei(Department of Pharmacy,West Carupus,Beijing Chao-Yang Hospital,Capital Medical Unirersity,Bejing 10000,China;Department of Pharmacy,Beijing Chao-Yang Hospital,Capital Medical Unirersity,Bejing 10000,China;Department of Pharmacy,The Rocket General Hospital People's Liberation Army,Beijing 10088,0 China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第7期711-715,共5页
The Chinese Journal of Clinical Pharmacology
基金
“十三五”重大新药创制课题基金资助项目(2017ZX09101001)。
