奈玛特韦原料药含量的定量核磁共振法测定

Determination of Nirmatrelvir by Quantitative Nuclear Magnetic Resonance

建立了测定奈玛特韦原料药绝对含量的定量核磁共振氢谱法(1H qNMR)。基于奈玛特韦在溶液中的构象稳定条件,以DMSO-D_(6)和D_(2)O(5∶1,体积比)为溶剂,δ4.96(1H,dd)和δ4.67(1H,dd)处的质子信号作为奈玛特韦的定量峰,δ6.22(1H,t)和δ5.84(1H,d)为拉米夫定的内标峰。样品与内标摩尔比在0.5∶1.0~1.2∶1.0范围时的线性拟合方程为Y=0.4564X-0.0005(r^(2)=0.9999),该方法专属性强,耐用性、重复性良好,回收率满足要求,稳定性可达48 h。该方法测得的奈玛特韦样品的含量为99.23%(相对标准偏差为0.24%)。^(1)H qNMR法操作简单,具有无损、准确快速的特点,适用于新药奈玛特韦绝对含量的测定。

A quantitative nuclear magnetic resonance(1H qNMR)method was developed for the de⁃termination of the absolute content of nirmatrelvir API.Based on the conformationally stable condi⁃tions of nemativir in solution,the proton signals atδ4.96(1H,dd),δ4.67(1H,dd)andδ6.22(1H,t),δ5.84(1H,d)were selected as the quantitative peaks for nirmatrelvir and lamivudine re⁃spectively in DMSO-D_(6) and D_(2)O(5∶1,by volume)solvents on BRUKER AV-500 NMR instrument.The qNMR method exhibited a high specificity,and an linear fitting equation Y=0.4564X-0.0005(r^(2)=0.9999)was obtained in the range of 0.5∶1.0-1.2∶1.0 for the molar ratio of sample to inter⁃nal standard,and the results showed good durability,reproducibility,recovery and 48-hour stabili⁃ty.The content of nirmatrelvir was determined to be 99.23%(RSD=0.24%)by qNMR.The 1H qNMR method is simple,non-destructive,accurate and rapid,which is suitable for determination on the absolute content of nirmatrelvir API.