【摘要】：采用液相色譜-線性離子阱-靜電場軌道阱高分辨質(zhì)譜(LC/LTQ-Orbitrap MS)技術(shù)研究候選藥物T-VA的裂解規(guī)律及體內(nèi)代謝,建立了大鼠體內(nèi)T-VA及其代謝產(chǎn)物的LC/MSn分析方法,分析討論了各自的主要碎片離子峰、質(zhì)譜特征與結(jié)構(gòu)信息,發(fā)現(xiàn)了血漿中主要代謝物M1。借鑒藥物化學(xué)的方法,合成得到了代謝產(chǎn)物實體M1-1,經(jīng)1 HNMR、13 CNMR、HRMS確認(rèn)其結(jié)構(gòu),根據(jù)其色譜、質(zhì)譜特征進(jìn)行驗證,結(jié)果表明,合成得到的M1-1即為血漿主要代謝物M1。借助PC12細(xì)胞模型驗證了代謝產(chǎn)物M1的神經(jīng)保護(hù)活性,該結(jié)果可為進(jìn)一步研究其生物轉(zhuǎn)化過程與前藥修飾提供重要信息。
[Abstract]:The pyrolysis law and in vivo metabolism of candidate drug T-VA were studied by liquid chromatography-linear ion trap electrostatic field orbital trap high resolution mass spectrometry (LC/LTQ-Orbitrap MS). A LC/MSn method for the analysis of T-VA and its metabolites in rats was established. The ion peaks of their main fragments, the characteristics and structural information of mass spectrometry were analyzed and discussed, and the main metabolites M _ 1 in plasma were found. Using the method of drug chemistry for reference, the metabolite entity M1 鈮，

本文編號：2496953