[交流] 【求助】求助，有哪些种类的代谢方式产生的代谢物极性比母药小？

已经请教一专家，但是至今未收到回复。所以在此请教你们。 现把邮件里的信息拷贝如下。时间紧，没有翻译过来。请见谅。 Dear Prof. Hsieh Y, I hope this mail will not surprise you. Up to now, I have read and studied several papers of you and consider you are a versatile scholar in pharmaceutical science. We absolutely believe you are expert in the application of mass spectrometry for metabolism studies. Therefore, we would like to send this mail to consult you for some questions in this field. Recently, we studied a polyphenolic natural product, illustrated in the following figure (AA), and found several metabolites of this compound in dog plasma. To our surprise, most of there metabolites are more hydrophobic compared with their parent compound. To our knowledge, metabolites including phase I and phase II are more hydrophilic than their parent drugs. We used C18-RP column to separate those metabolites and the natural product. Four metabolites were found in the dosed dog plasma. We have confirmed those metabolites by comparing the chromatograms form the plasma samples of the predosed dog. We have identified the glucuronide metabolite of the natural product. This identification has been illustrated in the figure. The other three metabolites exhibit longer retention time compared with their parent compound AA, which indicates that these metabolites are more hydrophobic than their parent compound. This observation has confused us and leads to difficulty in the identification of these metabolites. Could you tell us what metabolic pathways can generate the metabolites with more hydrophobic properties compared with their parent compounds? We will be grateful of your help and consideration sincerely. The figure has been appended to this mail followingly. Representative MRM chromatogram of AA in dosed dog plasma. Best wishes to you, Sincerely,

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