"ANALYTICAL SUPPORT AND PK SAMPLE ANALYSIS FOR PRECLINICAL PHARMACOLOGY STUDIES"

本任务指令旨在为NCI提供的血浆和/或肿瘤样本中的推定治疗药物的定量提供分析支持。还应在数据允许的范围内进行药代动力学分析。需要快速周转。该任务订单下有一个基本工作和九个选项。 承包商应为NCI提供的血浆和/或肿瘤样本中小分子抗癌剂的定量提供分析支持。这些样品可能来自小鼠的有效性或药效学研究或其他药理学/毒理学研究。 所有研究的活体部分将在其他NCI指定机构进行。假设出于成本计算的目的，将提供总共400个样品用于一种化合物的定量，并且将不超过两个基质（例如，血浆、肿瘤碎片）。 应针对基本任务开展以下具体活动： 1. 采用LC-MS/MS方法定量血浆和肿瘤样本中的化合物，并根据需要进行有限验证。应使用适合于发现研究的标准方法。假设药物样小分子约为300-900 MW。 2. 确定NCI提供给你的总共400个未知样本中的化合物水平。 运行适当的空白、标准品和QC样品。 将尽可能提供控制矩阵。 3. 非房室PK参数（Cmax、Tmax、AUC、t1/2、]等）应进行计算（如获得的数据所允许）。

The purpose of this Task Order is to provide analytical support for the quantification of putative therapeutic agents in plasma and/or tumor samples to be provided by NCI. Pharmacokinetic analysis to the extent allowed by the data shall also be performed. Rapid turn-around is required. There is a base effort and nine options under this task order. The contractor shall provide analytical support for the quantification of small-molecule anticancer agents in plasma and/or tumor samples to be provided by NCI. These samples may be derived from efficacy or pharmacodynamic studies in mice or other pharmacology/toxicology studies to be specified. The in-life portion of all studies will be conducted at other NCI-designated facilities. Assume for costing purposes that a total 400 samples will be provided for quantification of one compound and that there will be no more than two matrices (e.g., plasma, tumor fragments). The following specific activities shall be carried out for the Base Task: 1. Implement LC-MS/MS methodology for the quantification of the compounds in plasma and tumor samples and perform limited validation as required. Standard approaches suitable for discovery studies shall be used. Assume a drug-like small molecule of ~300-900 MW. 2. Determine levels of the compound in a total of 400 unknown samples to be provided to you by NCI. Run appropriate blanks, standards, and QC samples. Control matrix will be provided to the extent available. 3. Non-compartmental PK parameters (Cmax, Tmax, AUC, t1/2,], etc.) should be calculated (as permitted by the data obtained).