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Development and validation of an HPLC method for quantitation of BA-TPQ, a novel iminoquinone anticancer agent, and an initial pharmacokinetic study in mice.一种用于定量新型亚氨基醌抗癌剂BA-TPQ的高效液相色谱法的开发与验证以及在小鼠中的初步药代动力学研究。
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2
Development and validation of an HPLC-MS/MS analytical method for quantitative analysis of TCBA-TPQ, a novel anticancer makaluvamine analog, and application in a pharmacokinetic study in rats.一种用于新型抗癌马卡鲁胺类似物TCBA-TPQ定量分析的HPLC-MS/MS分析方法的建立与验证及其在大鼠药代动力学研究中的应用
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A novel synthetic iminoquinone, BA-TPQ, as an anti-breast cancer agent: in vitro and in vivo activity and mechanisms of action.新型合成亚胺醌 BA-TPQ 作为一种抗乳腺癌药物：体外和体内活性及作用机制。
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Highly efficient delivery of potent anticancer iminoquinone derivative by multilayer hydrogel cubes.多层水凝胶立方体高效递送强效抗癌亚胺醌衍生物
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Identification of the ZAK-MKK4-JNK-TGFβ signaling pathway as a molecular target for novel synthetic iminoquinone anticancer compound BA-TPQ.鉴定 ZAK-MKK4-JNK-TGFβ 信号通路为新型合成亚胺醌类抗癌化合物 BA-TPQ 的分子靶标。
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Preclinical evaluation of anticancer efficacy and pharmacological properties of FBA-TPQ, a novel synthetic makaluvamine analog.新型合成马卡鲁瓦明类似物 FBA-TPQ 的抗癌功效和药理学特性的临床前评价。
Mar Drugs. 2012 May;10(5):1138-1155. doi: 10.3390/md10051138. Epub 2012 May 23.
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Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy.通读化合物 13 可恢复肌营养不良症（Duchenne 型肌营养不良症）mdx 小鼠模型中的肌营养不良蛋白表达并改善肌肉功能。
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本文引用的文献

1
A novel synthetic iminoquinone, BA-TPQ, as an anti-breast cancer agent: in vitro and in vivo activity and mechanisms of action.新型合成亚胺醌 BA-TPQ 作为一种抗乳腺癌药物：体外和体内活性及作用机制。
Breast Cancer Res Treat. 2010 Sep;123(2):321-31. doi: 10.1007/s10549-009-0638-0. Epub 2009 Nov 21.
2
Synthesis and in vitro anti-lung cancer activity of novel 1, 3, 4, 8-tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogs.新型1,3,4,8-四氢吡咯并[4,3,2-de]喹啉-8(1H)-酮生物碱类似物的合成及其体外抗肺癌活性
Med Chem. 2009 May;5(3):227-36. doi: 10.2174/157340609788185873.
3
HPLC in natural product analysis: the detection issue.高效液相色谱法在天然产物分析中的检测问题。
Planta Med. 2009 Jun;75(7):719-34. doi: 10.1055/s-0028-1088393. Epub 2009 Jan 14.
4
Synthesis and antiproliferative activity of benzyl and phenethyl analogs of makaluvamines.马卡鲁胺的苄基和苯乙基类似物的合成及其抗增殖活性
Bioorg Med Chem. 2008 Mar 1;16(5):2541-9. doi: 10.1016/j.bmc.2007.11.051. Epub 2007 Nov 28.
5
Predicting oral clearance in humans: how close can we get with allometry?预测人体口服清除率：通过异速生长法我们能做到多接近实际情况？
Clin Pharmacokinet. 2008;47(1):35-45. doi: 10.2165/00003088-200847010-00004.
6
Key elements of bioanalytical method validation for small molecules.小分子生物分析方法验证的关键要素。
AAPS J. 2007 Mar 30;9(1):E109-14. doi: 10.1208/aapsj0901011.
7
Analogs of the marine alkaloid makaluvamines: synthesis, topoisomerase II inhibition, and anticancer activity.海洋生物碱马卡鲁胺类似物：合成、拓扑异构酶II抑制作用及抗癌活性。
Bioorg Med Chem Lett. 2007 May 15;17(10):2890-3. doi: 10.1016/j.bmcl.2007.02.065. Epub 2007 Feb 25.
8
Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.多种分析物的生物分析在药物发现与开发中的适用性：包括分析方法开发考量的精选案例研究综述
Biomed Chromatogr. 2006 May;20(5):383-414. doi: 10.1002/bmc.594.
9
Predicting pharmacokinetics and drug interactions in patients from in vitro and in vivo models: the experience with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an anti-cancer drug eliminated mainly by conjugation.通过体外和体内模型预测患者的药代动力学和药物相互作用：以5,6-二甲基呫吨酮-4-乙酸（DMXAA）为例，一种主要通过结合作用消除的抗癌药物的经验。
Drug Metab Rev. 2002 Nov;34(4):751-90. doi: 10.1081/dmr-120015693.
10
[Development of measurement of new quinolones in body fluids by HPLC using column switching and their application to drug interaction].[采用柱切换的高效液相色谱法测定体液中新型喹诺酮类药物及其在药物相互作用中的应用]
Yakugaku Zasshi. 2001 May;121(5):319-26. doi: 10.1248/yakushi.121.319.

一种用于定量新型亚氨基醌抗癌剂BA-TPQ的高效液相色谱法的开发与验证以及在小鼠中的初步药代动力学研究。

Development and validation of an HPLC method for quantitation of BA-TPQ, a novel iminoquinone anticancer agent, and an initial pharmacokinetic study in mice.

作者信息

Li Haibo, Ezell Scharri J, Zhang Xiangrong, Wang Wei, Xu Hongxia, Rayburn Elizabeth R, Zhang Xu, Gurpinar Evrim, Yang Xinyi, Sommers Charnell I, Velu Sadanandan E, Zhang Ruiwen

机构信息

Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.

College of Preventive Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.

出版信息

Biomed Chromatogr. 2011 May;25(5):628-634. doi: 10.1002/bmc.1498. Epub 2010 Sep 15.

DOI:10.1002/bmc.1498
PMID:20845374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3769168/
Abstract

We herein describe the development and validation of an HPLC method for the quantitation of 7-(benzylamino)-1,3,4,8-tetrahydropyrrolo [4,3,2-de]quinolin-8(1H)-one (BA-TPQ), a newly synthesized iminoquinone anticancer agent. BA-TPQ was extracted from plasma and tissue samples by first precipitating proteins with acetonitrile followed by a liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out using a gradient flow rate on a Zorbax SB C(18) column, and the effluent was monitored by UV detection at 346 nm. The method was found to be precise, accurate, and specific, with a linear range of 3.91-1955.0  ng/mL in plasma, 19.55-1955.0  ng/mL in spleen, brain, and liver homogenates and 19.55-3910.0  ng/mL in heart, lung and kidney homogenates. The method was stable under all relevant conditions. Using this method, we also carried out an initial study determining plasma pharmacokinetics and tissue distribution of BA-TPQ in mice following intravenous administration. In summary, this simple and sensitive HPLC method can be used in future preclinical and clinical studies of BA-TPQ.

摘要

我们在此描述了一种用于定量7-(苄基氨基)-1,3,4,8-四氢吡咯并[4,3,2 - de]喹啉-8(1H)-酮（BA-TPQ）的高效液相色谱（HPLC）方法的开发与验证，BA-TPQ是一种新合成的亚氨基醌类抗癌剂。通过先用乙腈沉淀蛋白质，然后用乙酸乙酯进行液-液萃取，从血浆和组织样品中提取BA-TPQ。使用Zorbax SB C(18)柱上的梯度流速进行色谱分离，并通过在346 nm处的紫外检测监测流出物。该方法被发现具有精密度高、准确性好和特异性强的特点，在血浆中的线性范围为3.91 - 1955.0 ng/mL，在脾脏、脑和肝脏匀浆中的线性范围为19.55 - 1955.0 ng/mL，在心脏、肺和肾脏匀浆中的线性范围为19.55 - 3910.0 ng/mL。该方法在所有相关条件下均稳定。使用此方法，我们还进行了一项初步研究，以确定静脉给药后小鼠体内BA-TPQ的血浆药代动力学和组织分布。总之，这种简单且灵敏的HPLC方法可用于未来BA-TPQ的临床前和临床研究。