近日,公安部禁du情報(bào)技術(shù)中心李靜老師,使用IPHASE品牌產(chǎn)品:人肝微粒體在《Biomedical Chromatography》全威期刊上發(fā)表文章《UPLC-HR-MS/MS-based determination study on the metabolism of four synthetic microsomes cannabinoids ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA, by human liver》,影響因子1.8!
本論文中提到:自2012年以來(lái),非法藥物市場(chǎng)上出現(xiàn)了幾種帶有纈氨基酸酰胺殘留的大ma模擬吲唑和吲哚衍生物,并逐漸用萘基或金剛烷基團(tuán),取代了老一代合成大ma素(SCs)。其中,ADB-FUBICA、AB-FUBICA、AB-BICA 和 ADB-BICA 最近在國(guó)內(nèi)被發(fā)現(xiàn),但遺憾的是,目前尚無(wú)關(guān)于其體外人體代謝的信息。因此,篩選其消費(fèi)的生物監(jiān)測(cè)研究缺乏有關(guān)潛在生物標(biāo)志物(例如代謝物)的任何信息,為了彌合這一差距,通過(guò)與人肝微粒體孵育來(lái)研究它們的I期代謝,并通過(guò)超高效液相色譜-高分辨率串聯(lián)質(zhì)譜(UPLC-HR-MS/MS)鑒定代謝物,發(fā)現(xiàn)1-氨基烷基部分的N-脫烷基化和羥基化產(chǎn)生的代謝物對(duì)這四種物質(zhì)均占主導(dǎo)地位,其他經(jīng)過(guò)羥基化、酰胺水解和脫氫的代謝物也在研究中被觀察到,根據(jù)研究,建議N-脫烷基化和羥基化代謝物是監(jiān)測(cè)其攝入量的合適和適當(dāng)?shù)姆治鰳?biāo)志物。
摘要
Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA were detected in China recently, but unfortunately no information about their in vitro human metabolism is available for now. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e.g.metabolites) to target. To bridge this gap, we investigated their phase I metabolism by incubating with human liver microsomes, and the metabolites were identified by Ultra Performance liquid chromatography-high resolution-tandem mass spectrometry (UPLC-HR-MS/MS). Metabolites generated by N-dealkylation and hydroxylation on the 1-amino-alkyl moiety were found to be predominant for all these four substances, and others which underwent hydroxylation, amide hydrolysis and dehydrogenation were also observed in our investigation. Based on our research, we recommend that the N-dealkylation and hydroxylation metabolites are suitable and appropriate analytical markers for monitoring their intake.
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