Determination of aqueous stability and degradation products of series of coumarin dimers

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• 作者：Snjež ; ana Dragojević ; Vitomir Š ; unjić ; Vlatka Bencetić ; -Mihaljević ; Jovica Ralić ; Milan Mesić ; Ivaylo Jivkov Elenkov ; Anita Filipović ; Su&#x10d ; i
• 关键词：Aqueous stability ; Coumarin dimers ; HPLC-DAD– ; MS analysis ; Decomposition rate ; Metabolic stability
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2011
• 出版时间：5 January 2011
• 年：2011
• 卷：54
• 期：1
• 页码：37-47
• 全文大小：1952 K

文摘

The stability in aqueous solution of five classes of coumarin dimers (I–V, compounds 1–29) was studied by HPLC–MS/MS at various pH values. The relationship between chemical structure and stability is discussed. It was found that dimeric compounds with strong electron withdrawing groups (EWGs) on the α-carbon to the bridging C-atom are stable at all pH values, whereas other derivatives undergo retro-Michael addition at rates which are also affected by the substituents on the aromatic rings. In some cases formation of stable isomers or oxidation products was observed. In order to evaluate their developability and potential for progression to in vivo studies, representative compounds were tested in an in vitro microsomal stability assay.