液相色谱-质谱联用同时测定人血浆中奈玛特韦、利托那韦及巴瑞替尼的浓度  

Simultaneous Determination of Nirmatrelvir,Ritonavir and Baricitinib Concentrations in Human Plasma by LC-MS/MS

作　　者：熊歆[1,2] 应颖秋 张现化[1,2] 刘维[1] 路明 陈静[4] 赵荣生[1,2] 周从亚[1,2] 杨平[1,2] 杨丽 赵立波 XIONG Xin;YING Ying-qiu;ZHANG Xian-hua;LIU Wei;LU Ming;CHEN Jing;ZHAO Rong-sheng;ZHOU Cong-ya;YANG Ping;YANG Li;ZHAO Li-bo(Department of Pharmacy,Peking University Third Hospital,Beijing 100191,China;Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University,Beijing 100191,China;Department of Respiratory and Critical Care Medicine,Peking University Third Hospital,Beijing 100191,China;Department of Infectious Disease,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]北京大学第三医院呼吸与危重医学科,北京100191 [4]北京大学第三医院感染疾病科,北京100191

出　　处：《中国药学杂志》2023年第11期1015-1019,共5页Chinese Pharmaceutical Journal

基　　金：北京大学第三医院新冠感染队列子任务资助(BYSYDL2023001-05);北京大学第三医院临床重点项目资助(BYSYZD2021002)。

摘　　要：目的建立同时测定人血浆中奈玛特韦、利托那韦和巴瑞替尼浓度的液相色谱-质谱联用法(LC-MS/MS),应用于检测新型冠状病毒感染患者的血药浓度。方法以沙奎那韦为内标,血浆经OstroTM除磷脂板进行前处理后,直接进行LC-MS/MS分析,色谱柱Waters Atlantis T3(2.1 mm×50 mm,3μm),流动相甲醇(含0.1%甲酸,5%水)-5 mmol·L^(-1)甲酸铵水溶液(含0.1%甲酸,5%乙腈),梯度洗脱,流速:0.3 mL·min-1,柱温40°C,进样量:0.5μL,电喷雾电离源,正离子模式,采用多反应监测模式,定量分析离子对分别为m/z 500.3→319.2(奈玛特韦),m/z 721.4→296.1(利托那韦),m/z 372.1→251.1(巴瑞替尼),m/z 671.5→570.4(沙奎那韦)。结果奈玛特韦线性范围在50~10000 ng·mL^(-1),利托那韦线性范围在10~2000 ng·mL^(-1),巴瑞替尼线性范围在1~200 ng·mL^(-1)。奈玛特韦、利托那韦和巴瑞替尼的批内和批间精密度(RSD%)均小于15%,准确度(RE%)均在±15%以内。此方法成功应用于临床新冠病毒感染合并肾功能不全患者的治疗药物监测。结论该方法灵敏,准确,简便,快速,可适用于奈玛特韦、利托那韦和巴瑞替尼的血药浓度监测。OBJECTIVE To develop a method for the simultaneous determination of nirmatrelvir,ritonavir and baricitinib,and apply the method for therapeutic drug monitoring in SARS-CoV-2-infected individuals.METHODS Using saquinavir as internal standard(IS),after extracted by OstroTM plate,the concentrations of nirmatrelvir,ritonavir and baricitinib in human plasma were detected by LC-MS/MS.The analytical column was Waters Atlantis T3(2.1 mm×50 mm,3μm)and the mobile phase was methanol(containing 0.1%formic acid and 5.0%water)-5 mmol·L^(-1) ammonium formate(containing 0.1%formic acid and 5.0%acetonitrile)under gradient elution at the flow rate of 0.3 mL·min-1.The column temperature was maintained at 40℃,and the injection volume was 0.5μL.The multiple reaction monitoring(MRM)was used to quantitatively analyze the ionization pairs as m/z 500.3→319.2(nirmatrelvir),m/z 721.4→296.1(ritonavir),m/z 372.1→251.1(baricitinib)and m/z 671.5→570.4(saquinavir).RESULTS The linear range of nirmatrelvir was 50-10000 ng·mL^(-1),ritonavir was 10-2000 ng·mL^(-1),and baricitinib was 1-200 ng·mL^(-1).For nirmatrelvir,ritonavir and baricitinib,the precisions(RSD%)of intra-day and inter-day were lower than 15%,the accuracies(RE%)were within±15%.This method was successfully applied to determine human plasma samples from patients with chronic renal dysfunction.CONCLUSION This developed method is sensitive,accurate,simple and rapid.It is suitable for the determination of nirmatrelvir,ritonavir and baricitinib in human plasma in clinical research.

关 键 词：液相色谱-质谱联用法 奈玛特韦 利托那韦 巴瑞替尼 治疗药物监测 

分 类 号：R969[医药卫生—药理学] R917[医药卫生—药学]