高效液相色谱法测定人血浆中奥希替尼的浓度  

Determination of osimertinib in human plasma by high performance liquid chromatography

作　　者：董馨蔚 倪美鑫 夏娴娴 王慧芳 朱罗晨 顾海娟 DONG Xin-wei;NI Mei-xin;XIA Xian-xian;WANG Hui-fang;ZHU Luo-chen;GU Hai-juan(Department of Pharmacy,Affiliated Tumor Hospital of Nantong University/Nantong Tumor Hospital,Nantong Jiangsu 226300)

机构地区：[1]南通大学附属肿瘤医院/南通市肿瘤医院药剂科,江苏南通226300

出　　处：《中南药学》2023年第12期3234-3238,共5页Central South Pharmacy

基　　金：南通市卫生健康委科研课题(No.QNZ2022030,No.MSZ2023039);江苏省研究型医院学会精益化用药石药专项科研项目(No.JY202233);南通大学临床医学专项项目(No.2022LY022)。

摘　　要：目的建立一种快速、简便检测人血浆中奥希替尼浓度的高效液相色谱法(HPLC),并应用于临床。方法色谱柱:Agilent InfinityLab Poroshell 120 EC-C18柱(4.6 mm×150 mm,4μm);流动相:磷酸二氢钾(pH 3.6)-乙腈=68.5:31.5(V/V),流速:1 mL·min^(-1);柱温:30℃,进样量:20μL。结果色谱图显示奥希替尼与杂质分离良好,奥希替尼线性范围是62.50~2500.00 ng·mL^(-1)(R2=0.9991);定量下限变异系数为4.4%;日内、日间精密度相对标准偏差小于8.0%,方法回收率在85%~115%,稳定性试验相对标准偏差小于10%,方法学考察符合要求。应用该方法对10位口服甲磺酸奥希替尼的非小细胞肺癌患者进行血药浓度检测,奥希替尼血药浓度在112.694~539.877 ng·mL^(-1)。结论该方法简便准确,成本低廉,可操作性强,可应用于临床奥希替尼血药浓度的检测。Objective To establish a rapid and simple method to determine osimertinib in human plasma by high performance liquid chromatography,and use it in clinical practice.Methods The column was Agilent InfinityLab Poroshell 120 EC-C18(4.6 mm×150 mm,4μm),the mobile phase was potassium dihydrogen phosphate(pH 3.6)-acetonitrile(68.5∶31.5,V/V)with a flow rate of 1 mL·min^(-1),the column temperature was 30℃,and the injection volume was 20μL.Results The chromatogram showed that osimertinib was well separated from the impurities.The linear ranges of plasma osimertinib concentrations was 62.50~2500.00 ng·mL^(-1)(R2=0.9991);the variation coefficients of the lower limit of quantification was 4.4%;the relative standard deviation of intraday and inter-day precision was less than 8.0%;the recovery rate was 85%~115%,and the relative standard deviation of stability test was less than 10%.The methodology met the requirements.The established method was used for 10 patients with non-small cell lung cancer who received osimertinib orally.The concentration of osimertinib in the plasma ranged 112.694~539.877 ng·mL^(-1).Conclusion This method is simple,accurate with low cost and highly manipulable,which is suitable for clinical detection of plasma osimertinib concentration.

关 键 词：高效液相色谱 奥希替尼 血药浓度 临床应用 

分 类 号：R96[医药卫生—药理学]