用高效液相色谱测定人血浆中西达本胺的浓度  

Determination of chidamide in human plasma by high performance liquid chromatography

作　　者：于佳鑫 付强[1,2] 刘鑫[1,2] 孙卓 许婷婷 梁春苏 张波[1,2] 左玮[1,2] YU Jia-xin;FU Qiang;LIU Xin;SUN Zhuo;XU Ting-ting;LIANG Chun-su;ZHANG Bo;ZUO Wei(Department of Pharmacy,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China;State Key Laboratory of Complex Severe and Rare Disease,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院药剂科,北京100730 [2]中国医学科学院北京协和医学院北京协和医院疑难重症及罕见病国家重点实验室,北京100730

出　　处：《中国临床药理学杂志》2024年第23期3449-3452,共4页The Chinese Journal of Clinical Pharmacology

基　　金：中央高水平医院临床科研业务费基金资助项目(2022-PUMCH-B-060)。

摘　　要：目的建立一种测定人血浆中西达本胺浓度的高效液相色谱方法。方法取血浆样品500μL,以曲安西龙为内标,用叔丁基甲醚进行液液萃取后,离心取上清液,氮气吹干后以水50μL复溶,再次离心后取10μL进样。色谱柱:Shim-pack CLC-ODS柱(150 mm×60 mm,5μm),流动相:水-乙腈=74∶26(冰醋酸调节pH=3),流速:1.0 mL·min^(-1),柱温:35℃,紫外检测波长:260 nm。考察该方法的专属性、标准曲线、定量下限、精密度、回收率和稳定性。此外,应用上述高效液相色谱法测定1例患者口服西达本胺后的血浆药物浓度。结果西达本胺及内标的保留时间分别为8.00和9.40 min。测定方法在0.01~1.00μg·mL^(-1)内,线性关系良好,其标准曲线方程为y=10.28x-0.06(r=0.998),低、中、高浓度质控样品(0.02、0.15、0.75μg·mL^(-1))的日内、日间精密度(RSD)为1.00%~4.87%(n=6),准确度在-10.29%~3.37%,平均提取回收率为61.74%~69.85%。结论本方法的灵敏度高,准确性好,简便快捷,适用于西达本胺的血药浓度监测。Objective To establish a high performance liquid chromatographic(HPLC)method for the determination of chidamide in human plasma.Methods The plasma sample was taken as 500μL,and triamcinolone was used as the internal standard.After liquid-liquid extraction using methyl tert-butyl ether,the supernatant was centrifuged and blown dry under N2,then re-dissolved in 50μL of water,and then centrifuged again,and then 10μL of the supernatant was injected into the system.The separation was performed on a Shim-pack CLC-ODS(150 mm×60 mm,5μm)at 35℃using water-acetonitrile=(74∶26,v/v,adjusted to pH=3 by acetic acid)as mobile phase.The flow rate was 1.0 mL·min^(-1) and the wavelength was 260 nm.The specificity,standard curve,lower limit of quantitation,precision,recovery and stability of the method were investigated.In addition,the high performance liquid chromatography method described above was applied to determine the plasma drug concentration after oral administration of chidamide in one patient.Results The retention time of chidamide and internal standard was 8.00 and 9.40 min,respectively.The standard curve equation was y=10.28x-0.06(r=0.998).The intra-day and inter-day precision(RSD)of low,medium and high concentration qua lit y control samples(0.02,0.15,0.75μg·mL^(-1))were 1.00%-4.87%(n=6),and the accuracy was-10.29%-3.37%.The average extraction recovery was 61.74%-69.85%.Conclusion The method was simple,sensitive and accurate,suitable for monitoring the concentrations of chidamide in human plasma.

关 键 词：西达本胺 高效液相色谱法 治疗药物监测 

分 类 号：R979.1[医药卫生—药品]