~1H-核磁共振定量法测定盐酸厄洛替尼含量

Determination of Erlotinib Hydrochloride by Proton Nuclear Magnetic Resonance

目的建立快速、准确的测定盐酸厄洛替尼含量的氢核磁共振定量分析方法。方法以马来酸为内标,DMSO-d6为溶剂,在测试温度为300℃,脉冲宽度9.54μs,弛豫时间20 s和扫描次数为64次条件下测定氢核磁共振谱,通过比较马来酸内标峰与盐酸厄洛替尼定量峰面积,从而计算出盐酸厄洛替尼含量。结果马来酸δ6.26处单峰信号作为内标峰,盐酸厄洛替尼δ8.84和δ8.47处作为定量峰,以两个定量峰面积的平均值计算盐酸厄洛替尼含量。盐酸厄洛替尼在2.88~19.08 mg·mL^(-1)浓度范围内与质子峰面积线性关系良好。精密度RSD为0.36%(n=6),重复性为0.83%(n=6),加样回收率为100.91%(n=6)。测得3批盐酸厄洛替尼含量含量分别为92.26%,91.94%和92.09%,平均含量为92.10%,RSD为0.17%。测定结果与质量平衡法定值结果基本一致。结论该方法操作简便、测定结果准确,为盐酸厄洛替尼的含量测定提供了新方法,适用于其原料药的质量控制。

ObjectiveTo establish a rapid and accurate method for quantitative determination of erlotinib hydrochloride by proton nuclear magnetic resonance(1H NMR).MethodsMaleic acid was used as an internal standard,and DMSO d6was employed as solvent.The pulse width was9.54μs,the delay time was20s,the scanning frequency was64and the testing temperature was set as300℃.Under this condition,the1H NMR data of the mixture of erlotinib hydrochloride and maleic acid were obtained.The content of erlotinib hydrochloride was calculated by comparing the response signal area of sample(As)and internal standard(Ar).ResultsProton signal peaked atδ8.84andδ8.47for erlotinib hydrochloride and atδ6.26for maleic acid served as quantitation peaks.The content of erlotinib hydrochloride was obtained by calculating the average of the test results of the two quantitative peaks.The concentration of erlotinib hydrochloride(2.88~19.08mg·mL-1)and the peak area of quantification peaks showed a good linear correlation.The precision RSD was0.36%(n=6),the repeatability RSD was0.83%(n=6)and the sample recovery was100.91%(n=6).The content of3batches of erlotinib hydrochloride was92.26%,91.94%and92.09%,the average was92.10%and its RSD was0.17%.The obtained results were generally consistent with those obtained from mass balance method.ConclusionThis established method is simple to handle as compared to traditional methods,and the analysis results are accurate.1H NMR provides a novel method for the determination of erlotinib hydrochloride and can be used for the quality control of erlotinib hydrochloride.