Analytical Method Develop.--Anticancer /Antiviral Agents

表征药剂的药代动力学的首要任务是具有用于定量生物液体和组织中药剂的可靠且可再现的分析方法。我们的研究工作一直致力于开发特异性靶向肿瘤的异常生物学的药剂，例如，改变的信号转导途径、血管生成的抑制或参与恶性表型发生的肽生长因子的结合。这些化合物的成功开发需要广泛使用药代动力学和药效学概念。此外，确定这些药剂在组织或血浆中的浓度在关联功效或毒性方面是极其重要的。这与标准细胞毒性药物的开发不同，在标准细胞毒性药物中，骨髓抑制是注意到的主要并发症，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转化药代动力学/药效学研究。这包括几个配备有光电二极管阵列检测器的液相色谱系统，这些检测器由HP Chemstation软件（在PC计算机上运行）控制，以及精密荧光、LC-MSD（质谱检测器）和电化学检测器。我们还利用GC技术，并与拥有NMR和AAS仪器的实验室合作。在某些情况下，ELISA和RIA是优选的定量方法。CPRC开发了监测TNP-470、苯乙酸、苯丁酸、他莫昔芬、UCN-01、CAI、沙利度胺、COL-3和辅酶Q10的分析方法。此外，我们还从生物体液中定量苏拉明、紫杉醇、美法仑、多西他赛、长春碱、哌立福辛、SU 5416、2 ME、MS 275、酮康唑、CC 5013和AZT。该实验室还在合作开发两种放射免疫分析方法：PSC 833和蓖麻毒素免疫毒素（CD 19和CD 22）。最后，CPRC在通过ELISA测量多种细胞因子和生长因子（VEGF、bFGF、TGFb、TNF、MMP 2、MMP 9）的血浆浓度中是有效的。

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).