液相色谱-串联质谱法检测人血浆中阿兹夫定的浓度  

Determination of Azvudine Concentration in Human Plasma by Liquid Chromatography-Mass Spectrometry

作　　者：张现化[1,2] 易湛苗 熊歆[1,2] 周从亚[1,2] 王晨 杨丽 王松[4] 王悦[4] 赵立波 赵荣生[1,2] ZHANG Xian-hua;YI Zhan-miao;XIONG Xin;ZHOU Cong-ya;WANG Chen;YANG Li;WANG Song;WANG Yue;ZHAO Li-bo;ZHAO Rong-sheng(Department of Pharmacy,Peking University Third Hospital,Beijing 100191,China;Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University,Beijing 100191,China;National Institutes for Food and Drug Control,Beijing 102629,China;Department of Nephrology,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院药剂科,北京100191 [2]北京大学治疗药物监测和临床毒理中心,北京100191 [3]中国食品药品检定研究院,北京102629 [4]北京大学第三医院肾内科,北京100191

出　　处：《中国药学杂志》2023年第15期1398-1402,共5页Chinese Pharmaceutical Journal

基　　金：北京大学第三医院新冠感染患者精准用药研究项目资助(BYSYDL2023001-05);北京大学第三医院临床重点项目资助(BYSYZD2021002)。

摘　　要：目的建立液相色谱-串联质谱法(LC-MS/MS)检测人血浆中阿兹夫定(azvudine,AZV)的浓度,并应用于新型冠状病毒感染患者的临床样本测定。方法血浆经OstroTM板除蛋白及磷脂后,以15N4-次黄嘌呤为内标,采用LC-MS/MS测定。色谱柱采用HILIC Silica柱,以乙腈(0.1%甲酸)-10 mmol·L^(-1)甲酸铵(0.1%甲酸及5%乙腈)为流动相进行梯度洗脱,流速0.30 mL·min^(-1),柱温40℃,进样量0.50μL。采用电喷雾离子源,以多反应监测模式进行正离子扫描,用于定量分析的离子对为m/z 287.3→112.0(AZV)、m/z 141.0→113.0(内标)。结果血浆中AZV在0.10~20.00 ng·mL^(-1)内线性良好,定量下限日内、日间相对标准偏差(RSD)均不大于4.46%,相对误差为12.00%~15.13%;低、中、高质控样本日内、日间RSD均不高于2.88%,相对误差为3.10%~12.11%。平均提取回收率为75.69%,基质效应及残留均不影响待测物的准确定量。该方法经验证后,成功应用于慢性透析合并新型冠状病毒感染患者血浆中AZV浓度的测定。结论本试验所建立的LC-MS/MS简单、灵敏、准确,可用于AZV的治疗药物监测。OBJECTIVE To establish an LC-MS/MS method for the determination of azvudine(AZV)concentration in plasma samples from patients with corona virus disease 2019(COVID-19).METHODS After protein precipitation and phospholipid removal with 96-well OstroTM plate,AZV in human plasma was determined by LC-MS/MS method.15N4-hypoxanthine was used as the internal standard(the IS).Gradient elution was performed on a HILIC silica column.The gradient mobile phase consisted of acetonitrile(0.1%formic acid)and 10 mmol·L^(-1)ammonium formate(0.1%formic acid and 5%acetonitrile)at a flow rate of 0.3 mL·min^(-1).The column temperature was maintained at 40℃and the injection volume was 0.50μL.An ESI source was used on positive mode.MRM transitions were m/z 287.3→112.0(AZV)and m/z 141.0→113.0(the IS).RESULTS The assay was linear within the range of 0.10-20.00 ng·mL^(-1).Intra-and inter-day precision for LLOQ was less than 4.46%and the relative error was 12.00%-15.13%.For quality control samples,the intra-and inter-day precisions were less than 2.88%and the relative error was 3.10%-12.11%.The average extraction recovery was 75.69%.The matrix effect and carryover were negligible.After validation,the method was applied to the determination of AZV in plasma of chronic dialysis patients with COVID-19.CONCLUSIONS The established LC-MS/MS method is simple,sensitive and accurate,and it can be applied to the therapeutic drug monitoring of AZV in clinical practice.

关 键 词：阿兹夫定 血药浓度 液相色谱-串联质谱法 治疗药物监测 

分 类 号：R969[医药卫生—药理学] R917[医药卫生—药学]