Pharmacokinetic and brain distribution study of an anti-glioblastoma agent in mice by HPLC-MS/MS.
Pharmacokinetic and brain distribution study of an anti-glioblastoma agent in mice by HPLC-MS/MS.
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DOI：
10.1002/bmc.5310
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发表时间：
2022-03
影响因子：
1.8
通讯作者：
Su, Bin
中科院分区：
文献类型：
--
作者：
Li, Yaxin;Dano, Raina;Li, Cathy;Zhang, Wenjing;Lathia, Justin D.;Wang, Bingcheng;Su, Bin
此前，化合物I在小鼠异种移植研究中显示出强大的抗胶质母细胞瘤活性，且没有毒性。本研究建立了一种灵敏、快速的高效液相色谱-串联质谱法(LC-MS/MS)，用于研究化合物I在小鼠体内的药代动力学和脑内分布。采用蛋白质沉淀法从小鼠血浆和脑匀浆中提取该化合物，采用Kinetex C18色谱柱，流动相为乙腈-0.1%甲酸水(50：50，v/v)。用多反应监测对分析物进行检测，以获得化合物的定量反应。日内、日间精密度分别为8.29%和3.85%，精密度在±7.33%以内。该方法已成功地应用于化合物I在小鼠血浆和脑组织中的药代动力学研究。结果表明，化合物I在血浆中的峰浓度在1h内达到峰值，表观消除半衰期为4.06h，脑组织中化合物I的峰值浓度为0.88μg/g，表明化合物I分布迅速，能通过血脑屏障。所得药代动力学曲线为进一步研究化合物I作为潜在的抗胶质母细胞瘤药物提供了有价值的信息。
Previously compound I showed great anti-glioblastoma activity without toxicity in a mouse xenograft study. In this study, a sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed and validated to investigate the pharmacokinetics and brain distribution of compound I in mice. The protein precipitation method was applied to extract the compound from mouse plasma and brain homogenates, and it was then separated using a Kinetex C18 column with a mobile phase consisting of acetonitrile–0.1% formic acid water (50:50, v/v). The analytes were detected with multiple reaction monitoring for the quantitative response of the compounds. The inter- and intra-day precisions were <8.29 and 3.85%, respectively, and the accuracy range was within ±7.33%. The method was successfully applied to evaluate the pharmacokinetics of compound I in mouse plasma and brain tissue. The peak concentration in plasma was achieved within 1 h. The apparent elimination half-life was 4.06 h. The peak concentration of compound I in brain tissue was 0.88 μg/g. The results indicated that compound I was rapidly distributed and could cross the blood–brain barrier. The pharmacokinetic profile summarized provides valuable information for the further investigation of compound I as a potential anti-glioblastoma agent.
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影响因子：
--
作者：
Zalcman N;Canello T;Ovadia H;Charbit H;Zelikovitch B;Mordechai A;Fellig Y;Rabani S;Shahar T;Lossos A;Lavon I
通讯作者：
Lavon I
DOI：
10.1186/s13046-018-0762-y
发表时间：
2018-04-27
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liu X;Feng C;Liu J;Cao L;Xiang G;Liu F;Wang S;Jiao J;Niu Y
通讯作者：
Niu Y
影响因子：
1.1
作者：
Davis ME
通讯作者：
Davis ME
影响因子：
4.8
作者：
Li, Jianzhuo;Fu, Xueqi;Zhang, Haitao
通讯作者：
Zhang, Haitao
影响因子：
51.1
作者：
Stupp, Roger;Hegi, Monika E.;Mirimanoff, Rene-Olivier
通讯作者：
Mirimanoff, Rene-Olivier