定量核磁共振波谱法测定坎地沙坦酯氨氯地平片中2个活性成分的绝对含量  

Determination of absolute contents of candesartan cilexetil and amlodipine besylate in candesartan cilexetil and amlodipine tablets by quantitative nuclear magnetic resonance

作　　者：张中玲 吴洪海[3] 陈忠奎 翁勤洁[4,5] ZHANG Zhong-ling;WU Hong-Hai;CHEN Zhong-kui;WENG Qin-jie(Polytechnic Institute of Zhejiang University,Hangzhou 31000,China;Hangzhou Leading Pharmatech Co.,Ltd.,Hangzhou 310058,China;College of Pharmaceutical Sciences Zhejiang University,Hangzhou 311100,China;GLP of Zhejiang University,Hangzhou 310058,China;Taizhou Institute of Zhejiang University,Taizhou 318001,China)

机构地区：[1]浙江大学工程师学院,杭州310000 [2]杭州先导医药科技有限责任公司,杭州310058 [3]浙江大学药学院,杭州311100 [4]浙江大学药物安全评价研究中心,杭州310058 [5]浙江大学台州研究院,台州318001

出　　处：《药物分析杂志》2024年第3期373-379,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立坎地沙坦酯氨氯地平片中坎地沙坦酯及苯磺酸氨氯地平2个活性成分绝对含量的定量核磁共振氢谱测定方法。方法:以坎地沙坦酯化学位移δ5.51,苯磺酸氨氯地平化学位移δ5.31为定量峰,马来酸化学位移δ6.27为内标定量峰,氘代二甲基亚砜(DMSO-d6)为溶剂,使用超导核磁共振波谱仪采集供试液的氢谱,对坎地沙坦酯氨氯地平片中坎地沙坦酯及苯磺酸氨氯地平2个活性成分绝对含量进行定量测定。结果:该方法专属性强,溶剂峰、水峰及辅料峰对待测定量峰无干扰。坎地沙坦酯在1.5800~9.4802 mg·mL^(-1)质量浓度范围内呈现良好的线性关系r=1.000,精密度、重复性及稳定性的RSD分别为0.070%、1.7%和0.68%,低、中、高浓度加标回收率在98.1%~99.2%;苯磺酸氨氯地平在0.9839~5.9036 mg·mL^(-1)质量浓度范围内呈现良好的线性关系(r=0.9999),精密度、重复性及稳定性的RSD分别为0.050%、1.8%和0.79%,低、中、高浓度加标回收率在99.1%~102.0%。运用该方法对2批参比制剂及不同来源的1批样品进行测试,坎地沙坦酯含量在98.10%~98.75%,苯磺酸氨氯地平含量在98.98%~99.60%。结论:该方法检测坎地沙坦酯氨氯地平片中2个活性成分的绝对含量快速、准确,且无需提供2个物质单组分对照品,为坎地沙坦酯氨氯地平片含量测定提供新的方法。Objective:To establish a method for determining the absolute contents of candesartan cilexetil and amlodipine besylate in candesartan cilexetil and amlodipine tablets by qNMR.Methods:The chemical shiftδ5.51 of candesartan cilexetil andδ5.31 of amlodipine besylate were used as the quantitative peaks.δ6.27 of maleic acid was the quantitative peak of internal standard.DMSO-d_6 was used as the solvent.Results:The method was highly specific and the solvent peak,water peak and excipient peaks did not interfere with the quantitative peaks.Candesartan cilexetil showed a good linear relationship in the concentration range of 1.5800-9.4802 mg·mL^(-1),r=1.000,RSDs of precision,repeatability and stability were 0.070%,1.7%and 0.68%,respectively.The recoveries of low,medium and high concentration spiked were 98.1%-99.2%.The linear range of amlodipine besylate was 0.9839-5.9036 mg·mL^(-1)(r=0.9999).The RSDs of precision,repeatability and stability were 0.050%,1.8%and 0.79%,respectively.The recovery of amlodipine besylate was 99.1%-102.0%.This method was used to test two batches of reference preparations and one batch of sample from different sources.The results showed that the content of candesatan cilexetil was between 98.10%to 98.75%,and that of amlldipine besylate was between 98.98%to 99.60%.Conclusion:This method is rapid and accurate and it is not necessary to use a single component reference substance.This method provides a new method to determine the content to candesartan cilexetil and amlodipine tablets.

关 键 词：坎地沙坦酯 苯磺酸氨氯地平 绝对含量 定量核磁共振法 

分 类 号：R917[医药卫生—药物分析学]