Toxicity evaluation of main zopiclone impurities based on quantitative structure–activity relationship models and in vitro tests

化学 遗传毒性 毒性 杂质 急性毒性 佐匹克隆 斑马鱼 体外 数量结构-活动关系 药理学 毒理 环境化学 生物化学 立体化学 生物 有机化学 基因 催眠药
作者
Yin Jie,Hairuo Wen,Hua Chen
出处
期刊:Journal of Applied Toxicology [Wiley]
卷期号:43 (2): 230-241 被引量:1
标识
DOI:10.1002/jat.4376
摘要

Toxicity evaluation of main zopiclone impurities can provide a basis for safety assessment and quality standards of zopiclone. In this study, the impurity profile of zopiclone was analyzed using forced degradation and related substances of zopiclone tablets using high-performance liquid chromatography (HPLC). Furthermore, various quantitative structure-activity relationship (QSAR) models were used to compare the toxicity, especially genotoxicity of two main zopiclone degradation impurities, namely, impurity B and 2-amino-5-chloropyridine. The predictive genotoxicity results were verified using an in vitro bacterial reverse mutation (Ames) test. Meanwhile, using zebrafish embryos as an animal model, zopiclone and its main impurities were analyzed at different concentrations, and their effects on zebrafish development, including embryonic teratogenesis and lethality, were examined. The results showed that impurity B and 2-amino-5-chloropyridine were the main degradation impurities of zopiclone; the latter's content increased with increase in the solution storage time. QSAR prediction and in vitro test results confirmed that both impurity B and 2-amino-5-chloropyridine were non-mutagenic and classified in the fifth impurity category. According to ICH M7 guidelines, these could be controlled as general non-mutagenic impurities. The relative toxicity to zebrafish embryo development was the highest for 2-amino-5-chloropyridine, followed by impurity B and zopiclone, and the malformation rate and mortality of embryos were concentration dependent. In conclusion, an increase in the control limit of 2-amino-5-chloropyridine is recommended when the quality standards of zopiclone materials and preparations are revised to ensure safety and quality control. The specific limit value of this impurity should be determined through further evaluation and research.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
shatang发布了新的文献求助10
1秒前
叽里呱啦完成签到 ,获得积分10
1秒前
1秒前
搞怪的滑板完成签到,获得积分10
2秒前
花开富贵发布了新的文献求助10
2秒前
周佳豪完成签到,获得积分10
3秒前
123456发布了新的文献求助10
4秒前
郑万恶完成签到,获得积分10
4秒前
zjw关闭了zjw文献求助
5秒前
xctdyl1992完成签到,获得积分10
5秒前
宫城百事顺完成签到,获得积分10
6秒前
耿大海发布了新的文献求助10
6秒前
7秒前
7秒前
7秒前
哈哈哈完成签到,获得积分20
8秒前
8秒前
青山完成签到,获得积分10
8秒前
mouxq发布了新的文献求助10
8秒前
小狗说好运来完成签到 ,获得积分10
10秒前
123321发布了新的文献求助10
10秒前
10秒前
12秒前
jerry发布了新的文献求助30
12秒前
shatang完成签到 ,获得积分10
14秒前
cc发布了新的文献求助10
14秒前
Florencia发布了新的文献求助10
14秒前
小郭子发布了新的文献求助10
14秒前
Orange应助LJQ采纳,获得10
15秒前
17秒前
小蘑菇应助王玉河采纳,获得10
21秒前
量子星尘发布了新的文献求助10
21秒前
zhy完成签到,获得积分10
22秒前
XXXX完成签到,获得积分10
23秒前
ding应助yuyy采纳,获得10
23秒前
9298488完成签到,获得积分10
25秒前
科研小白发布了新的文献求助10
26秒前
JamesPei应助菜菜一只采纳,获得10
27秒前
高分求助中
The Mother of All Tableaux Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 2400
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Cognitive Neuroscience: The Biology of the Mind (Sixth Edition) 1000
Optimal Transport: A Comprehensive Introduction to Modeling, Analysis, Simulation, Applications 800
Official Methods of Analysis of AOAC INTERNATIONAL 600
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3959547
求助须知:如何正确求助?哪些是违规求助? 3505776
关于积分的说明 11126213
捐赠科研通 3237706
什么是DOI,文献DOI怎么找? 1789252
邀请新用户注册赠送积分活动 871647
科研通“疑难数据库(出版商)”最低求助积分说明 802931