Study on Therapeutic Drug Monitoring Method of Risdiplam in Patients with Spinal Muscular Atrophy
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,2.6 μm),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 2 μL.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=0.999 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.Conclusion This method is easy,efficient and fast,which can be used for TDM of risdiplam in patients with spinal muscular atrophy.
spinal muscular atrophyrisdiplamUPLC-MS/MStherapeutic drug monitoringcontent determination
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