一、本课题的研究内容及目的基于HR0019这个新的化合物潜在的药理活性，我们需要对它进行药代动力学评价。
而为了准确评价其药理活性，我们必须开发一种该药物的分析方法，能够对其进行准确定量。
目前实验室已经完成了主要的方法开发，本次毕业设计主要是进行方法验证及方法调整。
研究内容主要有：1、对HR0019的HPLC-MS定量分析的方法开发，包括调试MS条件，调试HPLC条件。
2、对开发方法的验证，包括系统适用性、准确度、精密度、选择性、残留、基质效应、稀释可靠性、溶血效应、稳定性、回收率等。
二、主要成果形式 包括色谱条件、样品处理方式，以及方法验证的数据。
三、主要参考文献[1]Qiu,Qiyu;Domarkas,Juozas;Banerjee,Ranjita;Katsoulas,Athanasia;,cNamee,james P;Jean-Claude,Bertrand J.Type Ⅱcombi-molecules:design and binary targeting properties of the novel triazolinium-containing molecules JDD36 and JDE05.[J]ANTI-CABCER DRUGS.Volume 18(2),February 2007,pp 171-177.[2] Heather L.Watt, Zakaria Rachid, and Bertrand J. Jean-Claude.The Concept of Divergent Targeting through the Activation and Inhibition of Receptors as a Novel Chemotherapeutic Strategy: Signaling Responses to Strong DNA-Reactive CombinatorialMimicries.[J] Journal of Signal Transduction Volume 2012, Article ID 282050, 17 pages doi:10.1155/2012/282050.[3] 裴丽，罗艳，李翔，王丽伟。
《吉非替尼含量测定方法研究进展》实用药物与临床2013 年第16卷第7期。
[4] Structure-based ensemble-QSAR model: a novel approach to the study of the EGFR tyrosine kinase and its inhibitors.Xian-qiang SUN, Lei CHEN, Yao-zong LI, Wei-hua LI1, Gui-xia LIU1, Yao-quan TU, Yun TANG.[J]Acta Pharmacologica Sinica (2014) 35: 301310.[5] Malleshappa N. Noolvi* and Harun M. Patel.3D QSAR STUDIES ON A SERIES OF QUINAZOLINE DERRIVATIVES AS TYROSINE KINASE (EGFR) INHIBITOR: THE k-NEAREST NEIGHBOR MOLECULAR FIELD ANALYSIS APPROACH.[J] Journal of Basic and Clinical Pharmacy Vol-001 Issue-003 June 2010 August 2010 153-175.[6] Suman Rao, Anne-Laure Larroque-Lombard,Lisa Peyrard,Cdric Thauvin,Zakaria Rachid,Christopher Williams, Bertrand J. Jean-Claude. Target Modulation by a Kinase Inhibitor Engineered to Induce a Tandem Blockade of the Epidermal Growth Factor Receptor(EGFR) and c-Src: The Concept of Type III Combi-Targeting.[J] PLOS ONE,DOI:10.1371/journal.pone.0117215February 6,2015.[7] Synthesis of half-mustard combi-molecules with fluorescence properties: correlation with EGFR status. Zakaria Rachid, Fouad Brahimi, Juozas Domarkas and Bertrand Jacques Jean-Claude.[J] Bioorganic amp; Medicinal Chemistry Letters 15 (2005) 11351138.[8] A bioanalytical investigation on the exquisitely strong in vitro potency of theEGFRDNA targeting type II combi-molecule ZR2003 and its mitigated in vivo antitumour activity. Nahid Golabi, Fouad Brahimi, Ying Huang, Zakaria Rachid, Qiyu Qiu, Anne-Laure Larroque-Lombard,Bertrand J. Jean-Claude.[J]Journal of Pharmaceutical and Biomedical Analysis. Journal of Pharmaceutical and Biomedical Analysis 56 (2011) 592 599.[9] Ying Huang, Zakaria Rachid, Lisa Peyrard,Zhor Senhaji Mouhri, Christopher,Williams and Bertrand J. Jean-Claude.Positional Isomerization of A Non-Cleavable Combi-Molecule Dramatically Altered Tumor Cell Response Profile.[J]Chem Biol Drug Des 2015; 85: 153162[10] 谢楠_多靶点酪氨酸激酶抑制剂AL_8326抗肿瘤活性及机制研究 浙江大学硕士学位论文 [11] 吉非替尼可能通过EGFR启动子甲基化诱导肺腺癌细胞继发性耐药的研究_王起龙 中南大学硕士学位论文[12] Wang L，Lim MY，Chin T，et al． Ｒapid determination of gefitinib and its main metabolite,O-desmethyl gefitinib in human plasma using liquid chromatography-tandem mass spectrometry.［J］Journal of Chromatography B，2011，879( 22) : 2155-2161．[13] Guetens G，Prenen H，De Boeck G， et al． Sensitive and specific quantification of the anticancer agent ZD1839( Gefitinib) in plasma by on-column focusing capillary liquid chromatography-tandem mass spectrometry［J］． J Chromatogr A，2005，1082( 1) : 2-5．[14] Chahbouni A，Den Burger JC，Vos ＲM，et al． Simultaneous quantification of erlotinib，gefitinib，and imatinib in human plasma by liquid chromatography tandem mass spectrometry［J］． Ther Drug Monit，2009，31( 6) : 683-687．[15] Honeywell Ｒ，Yarzadah K，Giovannetti E，et al． Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry［J］.Journal of Chromatography B，2010，878( 15-16) : 1059-1068.四、工作进度3月1日~3月25日 资料查找，文献阅读；熟悉生物样品前处理的基本方法、方法验证的主要内容、HPLC-MS仪器操作以及方法开发的相关步骤。
以上是毕业论文文献综述，课题毕业论文、任务书、外文翻译、程序设计、图纸设计等资料可联系客服协助查找。
