Analytical Method Develop.--Anticancer /Antiviral Agents

分析方法开发--抗癌/抗病毒药物

• 批准号: 6558335
• 负责人: William Douglas Figg
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6558335
• 关键词: analytical chemistry; angiogenesis inhibitors; antineoplastics; antiviral agents; butyrates; chromatography; cofactor; drug screening /evaluation; enzyme linked immunosorbent assay; human tissue; immunoconjugates; melphalan; method development; paclitaxel; patient oriented research; pharmacokinetics; phenylacetates; phenylbutyrates; phenylcarboxylate; radioimmunoassay; spectrometry; staurosporine; suramin; tamoxifen; thalidomide; tissue inhibitor of metalloproteinases; vinblastine; zidovudine

The first priority in characterizing the pharmacokinetics of an agent is to have a reliable and reproducible analytical method for quantitating agents in biological fluids and tissues. Our research efforts have been devoted to the development of agents that specifically target the aberrant biology of neoplasms, e.g., altered signal transduction pathways, inhibition of angiogenesis, or binding of peptide growth factors involved in the genesis of the malignant phenotype. The successful development of such compounds requires extensive use of pharmacokinetic and pharmacodynamic concepts. In addition, determining the concentration of these agents in tissue or plasma is of the utmost importance in correlating efficacy or toxicity. This differs from the development of standard cytotoxic agents in which myelosuppression is the predominate complication noted and concentration analysis is not emphasized. Within the Clinical Pharmacology Research Core (CPRC), HPLC is often utilized to develop analytical methods. We use state of the art equipment to support our translational pharmacokinetic/ pharmacodynamic research. This includes several Liquid Chromatograph systems equipped with photo diode array detectors which are controlled by HP Chemstation software (run on pentium computers), as well as precision fluorescence, LC-MSD (mass spectroscopy detector), and electrochemical detectors. We also utilize GC techniques and collaborate with laboratories that have NMR and AAS instruments. In some cases, ELISA and RIA are the preferred method of quantification. The CPRC has developed analytical methods for monitoring TNP-470, phenylacetate, phenylbutyrate, tamoxifen, UCN-01, CAI, thalidomide, COL-3 and coenzyme Q10. Furthermore, we are also quantitating suramin, paclitaxel, melphalan, docetaxel, vinblastine, perifosine, SU5416, 2ME, MS275, ketoconazole, CC5013, and AZT from biological fluids. The laboratory is also working in collaboration on the development of two RIA assay methods: PSC 833 and ricin immunotoxins (CD19 and CD22). Lastly, the CPRC is active in measuring plasma concentrations of numerous cytokines and growth factors by ELISA (VEGF, bFGF, TGFb, TNF, MMP2, MMP9).

表征药物的药代动力学的首要任务是具有可靠且可再现的分析方法，用于定量生物流体和组织中的药物。我们的研究工作专门针对特异性针对肿瘤异常生物学的药物的发展，例如，信号转导途径改变，抑制血管生成或涉及恶性表型形成的肽生长因子的结合。成功开发此类化合物需要广泛使用药代动力学和药效学概念。另外，确定这些药物在组织或血浆中的浓度对于将功效或毒性相关联至关重要。这与标准的细胞毒性剂的发展不同，其中骨髓抑制是所指出的主要并发症，并且不强调浓度分析。在临床药理学研究核心（CPRC）中，HPLC通常用于开发分析方法。我们使用最先进的设备来支持我们的翻译药代动力学/药效研究。这包括配备了照片二极管阵列探测器的几种液态色谱系统，这些系统由HP ChemStation软件（在奔腾计算机上运行）以及精密荧光，LC-MSD（质谱检测器）和电化学检测器控制。我们还利用GC技术并与具有NMR和AAS仪器的实验室合作。在某些情况下，ELISA和RIA是定量的首选方法。 CPRC开发了用于监测TNP-470，苯乙酸酯，苯基丁酸，他莫昔芬，UCN-01，CAI，CAI，Thalidomide，Col-3和Coenzyme Q10的分析方法。此外，我们还在定量苏拉明，紫杉醇，梅尔法兰，多西他赛，长胶质素，perifosine，su5416、2ME，MS275，酮康唑，CC5013和AZT。该实验室还致力于开发两种RIA测定方法：PSC 833和Ricin免疫毒素（CD19和CD22）。最后，CPRC活跃于测量ELISA（VEGF，BFGF，TGFB，TNF，TNF，MMP2，MMP9）的众多细胞因子和生长因子的血浆浓度。