摘要
目的建立超高效液相色谱-串联质谱法测定大鼠血浆中伊马替尼及其代谢产物N-去甲伊马替尼的含量。方法用Waters Acquity色谱柱BEH C18(50 mm×2.1 mm,1.7μm),流动相为0.1%甲酸水溶液(A)-乙腈(B),梯度洗脱;流速为0.4 m L·min^(-1);电喷雾离子源,多反应监测。伊马替尼m/z 494.2→m/z 394.2,N-去甲伊马替尼m/z 480.2→m/z 394.2,内标卡马西平m/z 237.1→m/z 194.2。用乙腈沉淀法处理样品。8只SD大鼠灌胃伊马替尼10mg·kg^(-1)后,进行药代动力学研究。结果伊马替尼标准曲线方程为y1=1.2×10-3x1-2.58×10-2(r=0.998),线性范围为20~5000 ng·m L^(-1);N-去甲伊马替尼标准曲线方程为y2=0.5×10-3x2-4.3×10-3(r=0.993),线性范围为2.5~500 ng·m L^(-1)。两者日间、日内精密度均小于15%,伊马替尼方法回收率大于70%,N-去甲伊马替尼方法回收率在85%以上。结论该方法灵敏度高、专属性强,适用于血浆中伊马替尼及其代谢产物含量测定及药代动力学研究。
Objective to establish a UPLC-MS/MS method for the determination of imatinib and its main metabolite N-desmethyl imatinib in rat plasma. Methods The analytical column was Acquity BEH C18（ 50 mm ×2. 1 mm,1. 7 μm）. The mobile phase consisted of water containing0. 1% formic acid（ A） and acetonitrile（ B） with a linear gradient elution. The flow rate was 0. 4 m L·min^（-1）. A tandem mass spectrometer equipped with electrospray ionization source was used as detector with multiple reaction monitoring（ MRM）. Imatinib m/z 494. 2→m/z 394. 2,N-desmethyl imatinib m/z 480. 2 → m/z 394. 2,internal standard carbamazepine m/z 237. 1 →m/z 194. 2. The samples were protein precipitated with acetonitrile. And the pharmacokinetic study was performed after single oral administration of 10 mg · kg^（-1） imatinib to eight rats.Results The calibration curve of imatinib was y1= 1. 2 × 10-3 x1-2. 58 ×10-2（ r = 0. 998）,with the linear range of 20-5000 ng·m L^（-1）. The calibration curve of N-desmethyl imatinib was y2= 0. 5 × 10-3 x2-4. 3 × 10-3（ r = 0. 993）,with the linear range of 2. 5-500 ng·m L^（-1）.Intra-day and inter-day RSD for assaying the plasma sample were both 15 %,extraction recovery was 〉70 % for imatinib and 〉85 %for N-desmethyl imatinib. Conclusion The method is proved to be highly sensitive,selective,and suitable for investigations of imatinib and its main metabolite in plasma and pharmacokinetics.
作者
曹晓静
陈瑞杰
朱光辉
CAO Xiao-jing;CHEN Rui-jie;ZHU Guang-hui(Department of Pharmacy,The Second Affiliated and Yuying Children＇s Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2018年第17期2113-2116,共4页
The Chinese Journal of Clinical Pharmacology
基金
温州市科技局基金资助项目(Y20160537)
