本文選題：香豆素　切入點(diǎn)：-MOP　出處：《河南師范大學(xué)學(xué)報(bào)(自然科學(xué)版)》2017年02期 　論文類型：期刊論文

【摘要】：以香豆素為探針底物,建立了測(cè)定小鼠血液中香豆素及其代謝物的超高效液相色譜-軌道阱高分辨質(zhì)譜(UPLC-Orbitrap HRMS)法.以4-甲基傘形酮為內(nèi)標(biāo),樣品用乙腈沉淀蛋白后,直接進(jìn)入XDB-C_(18)色譜柱分離并采用一級(jí)全掃描和數(shù)據(jù)依賴二級(jí)掃描(Full MS/dd MS~2)模式進(jìn)行質(zhì)譜分析.通過測(cè)定7-羥基香豆素的生成量評(píng)估5-甲氧基補(bǔ)骨脂素(5-MOP)對(duì)小鼠CYP2A5酶活性的影響.結(jié)果表明:各目標(biāo)物的檢出限為0.011~0.016 ng/m L,回收率和日內(nèi)精密度分別為90.2%~110.4%和1.86%~7.08%.方法選擇性好,分析效率高,適合于小鼠血液中香豆素及其代謝物的測(cè)定.5-MOP組小鼠香豆素的最大血藥濃度Cmax為對(duì)照組的1.42倍(P0.01),藥時(shí)曲線下面積AUC0-∞為1.59倍(P0.05),半衰期t_(1/2)為1.05倍(P0.01),5-MOP能夠顯著抑制小鼠CYP2A5酶活性.
[Abstract]:Using coumarin as the probe substrate, an ultra-high performance liquid chromatography-orbital trap high resolution mass spectrometry (UPLC-Orbitrap HRMS) method was established for the determination of coumarin and its metabolites in blood of mice. Using 4-methylpara-ketone as internal standard, the protein was precipitated with acetonitrile. It was separated directly into XDB-Cn18) column and analyzed by mass spectrometry using full MS/dd MS2) mode. The activity of 5-methoxy psoralen 5-MOP was evaluated by determining the production of 7-hydroxycoumarin in mice, and the activity of 5-methoxy-psoralen 5-MOP in mice was evaluated by measuring the content of 7-hydroxy-coumarin (7-hydroxy-coumarin). The results showed that the detection limit of each target was 0.011 ~ 0.016 ng/m / L, the recovery rate and intra-day precision were 90.22 ~ 110.4% and 1.86 ~ 7.08, respectively. Analysis efficiency is high, The maximum blood concentration of coumarin in 5-MOP group was 1.42 times of that of control group (P 0.01), the area under the curve was 1.59 times (P 0.05), and the half-life of coumarin was 1.05 times (P 0.01 / 2), and the activity of CYP2A5 was significantly inhibited by 5-MOP.
【作者單位】： 中國(guó)煙草總公司鄭州煙草研究院;
【基金】：國(guó)家自然科學(xué)基金(21175153,21307163) 中國(guó)煙草總公司鄭州煙草研究院院長(zhǎng)科技發(fā)展基金項(xiàng)目(602011CA0310)
【分類號(hào)】：R-33;O657.63

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