氢核磁共振定量法测定伊立替康中间体含量  

Content Determination of Irinotecan Intermediate by Quantitative Hydrogen Nuclear Magnetic Resonance

作　　者：毛联岗 程青芳 MAO Liangang;CHENG Qingfang(JARI Pharmaceutical Co.,Ltd.,Lianyungang,Jiangsu,China 222000;School of Pharmacy,Jiangsu Ocean University,Lianyungang,Jiangsu,China 222005)

机构地区：[1]连云港杰瑞药业有限公司,江苏连云港222000 [2]江苏海洋大学药学院,江苏连云港222005

出　　处：《中国药业》2022年第8期92-95,共4页China Pharmaceuticals

基　　金：江苏省连云港高新区科技项目[ZD201917]。

摘　　要：目的建立测定伊立替康中间体盐酸1-氯甲酰基-4-哌啶基哌啶含量的氢核磁共振定量法。方法试验条件:内标为盐酸吉西他滨,内标峰为盐酸吉西他滨δ7.99,δ6.26,δ6.21处质子峰,定量峰为待测物δ2.38处质子峰,溶剂为重水;测定温度为22℃,激发脉冲角度为30°,采样32次,脉冲延迟时间为20 s,脉冲宽度为9.42μs,采样时间为3.2768 s,扫描宽度为10000 Hz,线宽因子为0.3 Hz,观测频率为500.11 MHz。结果待测样品和内标物质的量比在0.5106~1.9169范围内与待测样品和内标的峰面积比值线性关系良好(r=0.9973,n=6);精密度、稳定性、重复性试验的RSD均小于0.6%。氢核磁共振定量法测定的3批样品含量分别为98.38%,98.19%,98.25%,与质量平衡法结果的98.09%,97.70%,97.88%接近。结论所建立的方法专属性良好,可用于测定盐酸1-氯甲酰基-4-哌啶基哌啶的含量。ObjectiveTo establish a quantitative hydrogen nuclear magnetic resonance(qNMR)method for the content determination of 1-chloroformyl-4-piperidinylpiperidine hydrochloride(an intermediate of irinotecan).Methods follows:the internal standard substance was gemcitabine hydrochloride,the internal standard peak were proton peaks at δ7.99,δ6.26,and δ6.21 of gemcitabine hydrochloride,and the quantitative peak was the proton peak at δ2.38 of the sample to be tested,and the solvent was heavy water.The measured temperature was 22℃,the excitation pulse angle was 30°,the samples were taken 32times,the pulse delay time was 20 s,and the pulse width was 9.42μs.The sampling time was 3.2768 s,the scan width was 10000 Hz,the linewidth factor was 0.3 Hz,and the observation frequency was 500.11 MHz.ResultsThe amount of substance ratio of the sample to be tested and the internal standard substance had a good relationship with the peak area ratio of the sample to be tested and the internal standard substance in the range of 0.5106-1.9169(r=0.9973,n=6).The RSDs of precision,stability and repeatability tests were less than 0.6%.The contents of three batches of samples determined by qNMR were 98.38%,98.19% and 98.25%,which were close to 98.09%,97.70% and 97.88% of the results of the mass balance method.ConclusionThe established method has good specificity,which can be used for the content determination of 1-chloroformyl-4-piperidinylpiperidine hydrochloride.

关 键 词：氢核磁共振定量法 盐酸1-氯甲酰基-4-哌啶基哌啶 盐酸吉西他滨 含量测定 

分 类 号：R917[医药卫生—药物分析学] R979.1[医药卫生—药学]