高效液相色谱法测定人血清中甲磺酸阿帕替尼谷浓度  

Determination of apatinib mesylate trough concentration in human serum by high performance liquid chromatography

作　　者：张广全 阮建清 毕延智 薛宏波 何光照 ZHANG Guang-quan;RUAN Jian-qing;BI Yan-zhi;XUE Hong-bo;HE Guang-zhao(Department of Pharmacy,Changzhou Cancer Hospital of Soochow University,Jiangsu Changzhou 213032,China;College of Pharmaceutical Sciences,Soochow University,Jiangsu Suzhou 215123,China;Department of Oncology,Changzhou Cancer Hospital of Soochow University,Jiangsu Changzhou 213032,China)

机构地区：[1]苏州大学附属常州肿瘤医院药事科,江苏常州213032 [2]苏州大学药学院,江苏苏州215123 [3]苏州大学附属常州肿瘤医院肿瘤内科,江苏常州213032

出　　处：《中国医院药学杂志》2022年第19期2024-2027,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金青年基金项目(编号:81703596);常州市科技局科技计划项目(编号:CJ20219002)。

摘　　要：目的:建立灵敏、准确的高效液相色谱法用于检测人血清中甲磺酸阿帕替尼谷浓度。方法:选用凡德他尼作为内标,以乙酸乙酯作为提取剂,采用Shim-pack GIST C_(18)色谱柱(4.6 mm×250 mm,5μm);流动A相:0.2%三氟乙酸水溶液(1:499,V/V),流动B相:乙腈,采用梯度洗脱法,总运行时间20 min;流速1.0 mL·min^(-1);柱温30℃;检测波长260 nm。结果:甲磺酸阿帕替尼在20~1000 ng·mL^(-1)范围内血清中浓度与响应值之间呈现良好线性关系,线性方程为Y=0.0179X+0.0797(r=0.9999),最低定量限为20 ng·mL^(-1),提取回收率为79.9%~85.2%,4个不同质控浓度水平(最低定量限、低、中、高浓度)的日内和日间准确度为88.6%~105.4%,日内和日间精密度为2.0%~9.2%。血样短期稳定性、长期稳定性、3次冻融循环及血样处理后室温放置12 h稳定性良好。结论:该检测方法灵敏、准确,可用于甲磺酸阿帕替尼治疗药物监测研究。OBJECTIVE To establish a sensitive and accurate high performance liquid chromatography method for the determination of apatinib mesylate trough concentration in human serum.METHODS Vandetanil was employed as the internal standard,and ethyl acetate was used as the extractant.Gradient elution was performed on a Shim-pack GIST C_(18) column(4.6 mm×250 mm,5μm)with 0.2%trifluoroacetic acid aqueous solution(1:499,V/V)as the mobile phase A and acetonitrile as the mobile phase B at the flow rate of 1.0 mL·min^(-1),the column temperature was 30℃and the detection wavelength was 260 nm.The total running time was 20 min.RESULTS There was a good linear relationship between the serum concentration of apatinib mesylate and the response value within the range of 20^(-1)000 ng·mL^(-1).The linear equation was Y=0.0179X+0.0797(r=0.9999),and the lowest limit of quantitation was 20 ng·mL^(-1).The extraction recovery ranged from 79.9%to 85.2%.The accuracy and precision of intra-and inter-day for four different quality control levels(lowest limit of quantitation,and low,medium and high concentrations)ranged from 88.6%to 105.4%and 2.0%to 9.2%,respectively.The serum samples were stable during the short-term stability test,long-term stability test and three freeze-thaw cycles,and the treated serum samples were also stable after 12 h at room temperature.CONCLUSION The method is sensitive and accurate,which can be used for the study of therapeutic drug monitoring of apatinib mesylate.

关 键 词：甲磺酸阿帕替尼 谷浓度 高效液相色谱法 治疗药物监测 

分 类 号：R969.1[医药卫生—药理学]