UFLC-MS/MS法测定人血浆中阿帕替尼的药物浓度  

Determination of apatinib in human plasma by UFLC-MS/MS

作　　者：李昊[1] 孟雪 钱钊[1] 海鑫 LI Hao;MENG Xue;QIAN Zhao;HAI Xin(Department of Pharmacy,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院药学部,黑龙江哈尔滨150001

出　　处：《中国药物应用与监测》2023年第1期15-18,23,共5页Chinese Journal of Drug Application and Monitoring

基　　金：哈尔滨医科大学附属第一医院科研基金项目(2016B010)。

摘　　要：目的:建立一种灵敏度高、专属性强、便捷、高效的超快速液相色谱-质谱联用方法,用于测定人血浆中阿帕替尼药物浓度。方法:以伊马替尼作为内标物,采用乙腈沉淀血浆中的蛋白;色谱柱:Waters Bridge C_(18)柱(4.6 mm×150 mm,5μm);流动相为A-乙腈和B-1 mmol·L^(-1)甲酸铵,梯度洗脱(0~2.5 min 85%A,2.5~3 min 85%A~50%A,3~4 min 50%A);流速:1 mL·min^(-1);进样量:5μL;柱温:40℃;进样检测时间:4 min;采取ESI离子源,正离子模式下MRM扫描模式,阿帕替尼的离子对为m/z 398.2→212.2,内标的离子对为m/z 494.1→394.1。结果:阿帕替尼在20~1500 ng·mL^(-1)浓度范围内线性关系良好,r=0.999;日内、日间精密度均<15%,方法和提取回收率>90%,进样室、冻融、4℃条件下稳定性的RSD均<10%;患者血浆中阿帕替尼的浓度介于30.90~760.75 ng·mL^(-1)。结论:本实验建立的方法准确度高且操作简单,可在临床用于人血浆中阿帕替尼药物浓度的测定。Objective:To establish a high sensitive,specific,convenient and efficient method to determine the concentration of apatinib in patients’plasma by ultra fast liquid chromatography-mass spectrometry/mass spectrometry(UFLC-MS/MS).Methods:The internal standard was imatinib.Plasma pretreatment was performed by protein precipitation with acetonitrile.The chromatographic column was Waters Bridge C18(4.6 mm×150 mm,5μm).The mobile phase was A-acetonitrile and B-1 mmol·L^(-1)ammonium formate,samples were gradiently eluted(0-2.5 min elution ratio of 85%A,2.5–3 min elution ratio of 85%A-50%A,3-4 min elution ratio of 50%A).Theflow rate was 1 mL·min^(-1).The injection volume was 5μL.The column temperature was 40℃.And the total detection time was 4 min.The multiple reaction monitoring(MRM)mode under positive ion with electrospray ionization(ESI)were adopted in the detection.The ion pair of apatinib and imatinib were m/z 398.2→212.2 and m/z 494.1→394.1 respectively.Results:The linear range of regression equation was from 20 to 1500 ng·mL^(-1)for apatinib(r=0.999).The intra-and inter-day precision were less than 15%.The recoveries and extraction recoveries of the method were both more than 90%.The relative standard deviation(RSD)of the samples at room temperature,freezing and 4°C were all less than 10%.The concentration of apatinib in the plasma of patients were between 30.90 and 760.75 ng·mL-1.Conclusion:The method established in this experiment was accurate and easy to operate,which could be used in clinic for the determination of apatinib drug concentration in human plasma.

关 键 词：阿帕替尼 伊马替尼 治疗药物监测 UFLC-MS/MS 

分 类 号：R917[医药卫生—药物分析学] R979.1[医药卫生—药学]