Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish
Cefazolin sodium is an essential drug that is widely used in clinical therapy for certain infective diseases caused by bacteria. As drug impurities are considered to be one of the most important causes of drug safety issues, we studied embryotoxicity, cardiotoxicity, and neurotoxicity of nine cefazo...
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doaj-abc5d04190574853acc386eb7715108e2020-11-24T22:29:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-06-01810.3389/fphar.2017.00403266291Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in ZebrafishBo Chen0Zhu-Qing Gao1Ying Liu2Yang-Min Zheng3Ying Han4Jing-Pu Zhang5Chang-Qin Hu6Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, ChinaDivision of Antibiotics, National Institutes for Food and Drug Control, Graduate School of Peking Union Medical CollegeBeijing, ChinaDivision of Antibiotics, National Institutes for Food and Drug Control, Graduate School of Peking Union Medical CollegeBeijing, ChinaDepartment of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, ChinaDivision of Antibiotics, National Institutes for Food and Drug Control, Graduate School of Peking Union Medical CollegeBeijing, ChinaDepartment of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, ChinaDivision of Antibiotics, National Institutes for Food and Drug Control, Graduate School of Peking Union Medical CollegeBeijing, ChinaCefazolin sodium is an essential drug that is widely used in clinical therapy for certain infective diseases caused by bacteria. As drug impurities are considered to be one of the most important causes of drug safety issues, we studied embryotoxicity, cardiotoxicity, and neurotoxicity of nine cefazolin sodium impurities in zebrafish embryo and larvae for the objective control of impurity profiling. LC-MS/MS was employed to analyze the compound absorbance in vivo, and the structure-toxicity relationship was approached. Our results suggested that the structure of MMTD (2-mercapto-5-methyl-1, 3, 4-thiadiazole) is the main toxic functional group for embryo deformities; the 7-ACA (7-aminocephalosporanic acid) structure mainly affects motor nerve function; and both the MMTD and 7-ACA structures are responsible for cardiac effects. Impurity G (7-ACA) presented with the strongest toxicity; impurity A was most extensively absorbed to embryo and larvae; and impurity F (MMTD) exhibited the strongest apparent toxic effect; Therefore, impurities F and G should be monitored from the cefazolin sodium preparations.http://journal.frontiersin.org/article/10.3389/fphar.2017.00403/fullcefazolinimpuritiesstructure-toxicity correlationtoxicity evaluationzebrafish |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo Chen Zhu-Qing Gao Ying Liu Yang-Min Zheng Ying Han Jing-Pu Zhang Chang-Qin Hu |
spellingShingle |
Bo Chen Zhu-Qing Gao Ying Liu Yang-Min Zheng Ying Han Jing-Pu Zhang Chang-Qin Hu Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish Frontiers in Pharmacology cefazolin impurities structure-toxicity correlation toxicity evaluation zebrafish |
author_facet |
Bo Chen Zhu-Qing Gao Ying Liu Yang-Min Zheng Ying Han Jing-Pu Zhang Chang-Qin Hu |
author_sort |
Bo Chen |
title |
Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish |
title_short |
Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish |
title_full |
Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish |
title_fullStr |
Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish |
title_full_unstemmed |
Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish |
title_sort |
embryo and developmental toxicity of cefazolin sodium impurities in zebrafish |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2017-06-01 |
description |
Cefazolin sodium is an essential drug that is widely used in clinical therapy for certain infective diseases caused by bacteria. As drug impurities are considered to be one of the most important causes of drug safety issues, we studied embryotoxicity, cardiotoxicity, and neurotoxicity of nine cefazolin sodium impurities in zebrafish embryo and larvae for the objective control of impurity profiling. LC-MS/MS was employed to analyze the compound absorbance in vivo, and the structure-toxicity relationship was approached. Our results suggested that the structure of MMTD (2-mercapto-5-methyl-1, 3, 4-thiadiazole) is the main toxic functional group for embryo deformities; the 7-ACA (7-aminocephalosporanic acid) structure mainly affects motor nerve function; and both the MMTD and 7-ACA structures are responsible for cardiac effects. Impurity G (7-ACA) presented with the strongest toxicity; impurity A was most extensively absorbed to embryo and larvae; and impurity F (MMTD) exhibited the strongest apparent toxic effect; Therefore, impurities F and G should be monitored from the cefazolin sodium preparations. |
topic |
cefazolin impurities structure-toxicity correlation toxicity evaluation zebrafish |
url |
http://journal.frontiersin.org/article/10.3389/fphar.2017.00403/full |
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