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δ 5.51,苯磺酸氨氯地平化学位移δ 5.31为定量峰,马来酸化学位移δ 6.27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1.580 0~9.480 2 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0.983 9~5.903 6 mg·mL-1质量浓度范围内呈现良好的线性关系(r=0.999 9),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 shift δ 5.51 of candesartan cilexetil and δ 5.31 of amlodipine besylate were used as the quantitative peaks. δ 6.27 of maleic acid was the quantitative peak of internal standard. DMSO-d6 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 1.580 0- 9.480 2 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 0.983 9-5.903 6 mg·mL-1 (r=0.999 9). 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.
[1] 全球高血压报告:与无声杀手的竞赛[R]. 日内瓦:世界卫生组织, 2023
Global Report on Hypertension: the Race Against a Silent Killer[R]. Geneva: World Health Organization; 2023
[2] 房静. 坎地沙坦酯片的制备及质量控制[D]. 天津:天津医科大学,2021
FANG J. The Preparation and Quality Control of Candesartan Cilexetil Tablets[D]. Tianjin:Tianjin Medical University, 2021
[3] 马永义. 苯磺酸氨氯地平的质量研究[D]. 长春:吉林大学,2006
MA YY. Quality of Amlodipine Besylate[D]. Changchun: Jilin University, 2006
[4] 叶兴龙. 沙坦类血管紧张素受体阻滞剂联用钙拮抗剂治疗糖尿病并发高血压进展[J]. 中国民康医学,2012,24(24):3055
YE XL. Saltan angiotensin receptor blockers in combination with calcium antagonists for the treatment of diabetes mellitus complicated by hypertension progression[J]. Med J Chin People's Health, 2012, 24(24):3055
[5] 刘莉,叶鹏. 血管紧张素受体拮抗剂与钙拮抗剂或利尿剂联用对家庭血压变异性的影响[J]. 中华高血压杂志,2012,20(6):529
LIU L, YE P. Effect of angiotensin receptor antagonists in combination with calcium antagonists or diuretics on blood pressure variability in families[J]. Chin J Hypertens, 2012, 20(6):529
[6] 毛柯,陈宁,卢定强. 坎地沙坦酯氨氯地平片含量测定[J]. 药学与临床研究,2014,22(3):226
MAO K, CHEN N, LU DQ. Content determination of candesartan cilexetil and amlodipine tablets by HPLC[J]. Pharm Clin Res, 2014, 22(3):226
[7] 赵晓妍,李丽. 坎地沙坦酯氨氯地平片中两种组分的含量测定[J]. 医药导报,2012,31(9):1203
ZHAO XY, LI L. Determination of two components in candesartan cilexetil and amlodipine besylate combination tablets[J]. Herald Med, 2012, 31(9):1203
[8] BELAL TS, MAHROUS MS, ABDEL-KHALEK MM, et al. Validated spectrofluorimetric determination of two pharmaceutical antihypertensive mixtures containing amlodipine besylate together with either candesartan cilexetil or telmisartan [J]. Luminescence (Chichester, England), 2014, 29 (7): 893
[9] 中华人民共和国药典2020 年版.四部[S]. 2020:53
ChP 2020. Vol Ⅳ[S]. 2020:53
[10] 宋春辉,刘翠梅,贾薇,等. 低场和高场核磁共振技术用于甲基苯丙胺及其掺杂物定量分析[J]. 药物分析杂志,2023,43(5):793
SONG CH, LIU CM, JIA W, et al. Quantitative analysis of methamphetamine and adulterants by low-field and high-field NMR[J]. Chin J Pharm Anal, 2023, 43(5):793
[11] 刘静,冯玉飞,刘阳,等. 核磁共振技术在首批中药化学对照品研制中的应用[J]. 中国现代中药,2022,24(2):298
LIU J, FENG YF, LIU Y, et al. Application of nuclear magnetic resonance in development of first batch of traditional chinese medicine chemical reference substances[J]. Mod Chin Med, 2022, 24(2):298
[12] 闫慧娇,王志伟,林云良,等. 氢核磁定量分析技术测定人参皂苷Rd对照品含量的研究[J]. 山东科学,2018,31(4):26
YAN HJ, WANG ZW, LIN YL, et al. Quantitative 1H NMR based content determination of ginsenoside Rd[J]. Shandong Sci,2018,31(4):26
[13] FOTAKIS C, CHRISTODOULEAS D, ZOUMPOULAKIS P, et al. Comparative biophysical studies of sartan class drug molecules losartan and candesartan (CV-11974) with membrane bilayers[J]. J Phys Chemy B, 115(19): 6180
[14] REFAT MS, AL-SAIF FA. Mononuclear transition and non-transition complexes of amlodipine besylate as antihypertensive agent: synthesis, spectral, thermal, and antimicrobial studies[J]. Res Chem Intermed, 2015, 41:1421
[15] JP 18 [S]. 2021:615
[16] 裴云山. 蛋白质二硫键异构酶与小分子抑制剂及客户蛋白相互作用的核磁共振波谱研究[D]. 北京:中国科学院大学(中国科学院精密测量科学与技术创新研究院),2022
PEI YS. Study on the Interaction of Protein Disulfide Isomerase with Small Molecule Inhibitor and Client Proteins by NMR[D]. Beijing:University of Chinese Academy of Sciences, 2022
[17] 李永利,陈鹰,李杰. 反门控去耦技术-定量核磁共振法测定染料木素的含量[J]. 理化检验-化学分册,2022,58(6):629
LI YL, CHEN Y, LI J. Content determination of genistein by the method of inverse gated decoupling technique and quantitative NMR[J]. Phys Test Chem Anal (Part B:Chem Anal), 2022, 58(6):629
[18] 孙余娟. 核磁共振技术检测乳制品中兽药残留的研究[D]. 天津:天津理工大学,2021
SUN YJ. Detection of Veterinary Drug Residues In Dairy Products by Nuclear Magnetic Resonance[D]. Tianjin:Tianjin University of Technology, 2021
[19] 李彭,赵阳,赵彦彪,等. 核磁共振技术及定量核磁共振技术在毒品分析中的应用(英文)[J]. 刑事技术,2017,42(4):312
LI P, ZHAO Y, ZHAO YB, et al. NMR and qNMR for drug analysis[J]. Forensic Sci Technol, 2017, 42(4):312
