Using photoreactivity studies to provide insight into the photosafety of pharmaceutical therapies

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• 作者：Mark H. Kleinman
• 关键词：3T3 NRU ; 3T3 Neutral Red Uptake phototoxicity test ; API ; Active pharmaceutical ingredient ; DP ; Drug product ; RNO ; N ; N-dimethyl-p-nitrosodimethylaniline ; ROS ; Reactive oxygen species ; SAR ; Structure-activity relationship
• 刊名：TrAC Trends in Analytical Chemistry
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：49
• 期：Complete
• 页码：100-107
• 全文大小：924 K

文摘

This review provides a framework that builds on the experimental design of photostability studies with the aim of improving their relevancy to photosafety studies. To this end, the mechanistic bases of the photodegradation-stress test, reactive oxygen species (ROS) assays, are discussed. Correlation between these studies and the 3T3 Neutral Red Uptake (3T3 NRU) phototoxicity test is explored. It is suggested that, in addition to the stress tests described in ICH Q1B, it is important to run the photostress forced degradation studies with the same light exposure as in the 3T3 NRU phototoxicity test. A decision tree that illustrates the relevant studies from analytical science has been constructed to support photosafety assessment in the pharmaceutical industry. Understanding the mechanistic relationship between the analytical stability and ROS assay in the context of the 3T3 NRU phototoxicity test can help analytical scientists contribute to multidisciplinary photosafety discussions.