【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Phenomenex 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=0.999 1,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。更多还原

【Abstract】 Objective To establish a therapeutic drug monitoring （TDM） method of risdiplam in patients with spinal muscular atrophy.MethodsUltra-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 was0.07%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）.ResultsThe linear range of risdiplam was1.95-125.00 ng/mL （R²=0.999 1,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.ConclusionThis method is easy,efficient and fast,which can be used for TDM of risdiplam in patients with spinal muscular atrophy.更多还原