title: [Analysis and evaluation of the impurity of felodipine and its tablets].
abstract: The paper reports the systematic study on felodipine and its impurities in tablets, to improve its quality standards for the control of the related substances. HPLC-DAD, UPLC-MS, IR and NMR methods were used for the isolation of felodipine and its impurities in tablets, their identification and the zebrafish animal model was used for the analysis of the toxic impurities. In felodipine material and its tablets, three impurities are isolated and identified. They are impurity 1 [dimethyl 4-(2, 3-dichlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate], impurity 2 [ethyl methyl 4-(2, 3-dichlorophenyl)-2, 6-dimethylpyridine-3, 5-dicarboxylate] and impurity 3 [diethyl 4-(2, 3-dichlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate], separately. The result of zebrafish animal model analysis showed that the teratogenic effects of four compounds were: impurity 3 > or = felodipine > impurity 1 > impurity 2, lethal effects were as follows: impurity 2 = impurity 3 > felodipine > or = impurity 1. This study confirmed the toxicity of three impurities in felodipine. According to the results, the paper suggested the amendments to the standard of the medicine and provided the support to the control of impurities in the manufacturing process.
authors.affiliation: National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Li-Ju
authors.initials: LJ
authors.lastname: Yu
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Tong
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Zhang
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Shi
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D015736:Felodipine / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D011786:Quality Control; D013055:Spectrophotometry, Infrared; D013607:Tablets; D053719:Tandem Mass Spectrometry; D015027:Zebrafish
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004364:Pharmaceutical Preparations; D013607:Tablets; D015736:Felodipine