脊髓性肌萎缩症患者利司扑兰治疗药物监测方法研究  

Study on Therapeutic Drug Monitoring Method of Risdiplam in Patients with Spinal Muscular Atrophy

作　　者：吴献 黄晓会[2] 林志燕[2] 刘艳[2] 蒋文高[1] 刘昕竹 张健 WU Xian;HUANG Xiaohui;LIN Zhiyan;LIU Yan;JIANG Wengao;LIU Xinzhu;ZHANG Jian(College of Pharmacy,Chongqing Medical University,Chongqing,China 400016;Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China 200092)

机构地区：[1]重庆医科大学药学院,重庆400016 [2]上海交通大学医学院附属新华医院,上海200092

出　　处：《中国药业》2024年第12期58-61,共4页China Pharmaceuticals

基　　金：中国药学会医院药学专业委员会人才专项资助项目[CPA-Z05-ZC-2022-003];教育部·上海市生物医药临床研究与转化协同创新中心重点科研项目[CCTS-2022205]。

摘　　要：目的建立脊髓性肌萎缩症患者利司扑兰治疗药物监测的方法。方法采用超高效液相色谱串联质谱法,色谱柱为Phe‐nomenex Kinetex XB C18柱(50 mm×3 mm,2.6µm),流动相为0.07%甲酸水溶液(pH 4.5)-0.07%甲酸乙腈溶液(pH 5.5),梯度洗脱,流速为0.3 mL/min,柱温为40℃,进样量为2µL;采用电喷雾离子源(正离子模式),多反应监测模式,利司扑兰的离子对m/z分别为402.2→319.2、402.2→374.4,RG7800的离子对m/z为417.3→360.2。结果利司扑兰质量浓度在1.95~125.00 ng/mL范围内与其峰面积与内标峰面积比值线性关系良好(R2=0.9991,n=8),定量限为1.95 ng/mL;基质效应试验结果的变异系数均小于12%;精密度、稳定性试验结果的RSD均小于20%,准确度分别为87%~108%、87%~113%。6例患者利司扑兰血药浓度为13.03~91.14 ng/mL。结论该方法操作简便、高效快速,可用于脊髓性肌萎缩症患者利司扑兰的治疗药物监测。Objective To establish a therapeutic drug monitoring(TDM)method of risdiplam in patients with spinal muscular atrophy.Methods Ultra-high-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)was adopted,the chromatographic column was the Phenomenex Kinetex XB C18 column(50 mm×3 mm,2.6µm),the mobile phase was 0.07%formic acid aqueous solution(pH 4.5)-0.07%formic acid acetonitrile solution(pH 5.5)with gradient elution,the flow rate was 0.3 mL/min,the column temperature was 40℃,and the injection volume was 2µL.The electro-spray ionization was adopted with positive ion mode and multiple reaction monitoring mode.The mass-to-charge ratios(m/z)were 402.2→319.2(risdiplam),402.2→374.4(risdiplam)and 417.3→360.2(RG7800).Results The linear range of risdiplam was 1.95-125.00 ng/mL(R2=0.9991,n=8).The limit of quantitation was 1.95 ng/mL.The coefficient of variation of the matrix effect test was lower than 12%.The RSDs of precision and stability tests were lower than 20%,with accuracy ranging from 87%to 108%and 87%to 113%,respectively.The plasma concentration of risdiplam in six patients was in the range of 13.03 to 91.14 ng/mL.Conclusion This method is easy,efficient and fast,which can be used for TDM of risdiplam in patients with spinal muscular atrophy.

关 键 词：脊髓性肌萎缩症 利司扑兰 超高效液相色谱串联质谱法 治疗药物监测 含量测定 

分 类 号：R917[医药卫生—药物分析学]