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

“临床前药理学研究的分析支持和 PK 样品分析”

• 批准号: 10037669
• 负责人: JAN BEUMER
• 金额: $ 2.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2024-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10037669
• 关键词: Antineoplastic Agents; Contractor; Data; Drug Kinetics; Life; Methodology; Mus; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology Study; Pharmacology and Toxicology; Plasma; Running; Sampling; Specific qualifier value; Therapeutic Agents; Validation; base; cost; pre-clinical; small molecule; tumor

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).

本任务指令的目的是为 NCI 提供的血浆和/或肿瘤样本中推定治疗药物的定量提供分析支持。还应进行数据允许范围内的药代动力学分析。需要快速周转。此任务订单下有一项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药物的定量提供分析支持。这些样品可能来自小鼠的功效或药效学研究或其他指定的药理学/毒理学研究。 所有研究的现实部分将在 NCI 指定的其他设施中进行。出于成本核算的目的，假设将提供总共 400 个样品用于量化一种化合物，并且基质不超过两个（例如血浆、肿瘤碎片）。 基础任务应开展以下具体活动： 1. 采用 LC-MS/MS 方法对血浆和肿瘤样品中的化合物进行定量，并根据需要进行有限验证。应使用适合发现研究的标准方法。假设约 300-900 MW 的药物样小分子。 2. 确定 NCI 向您提供的总共 400 个未知样品中化合物的含量。 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. 应计算非房室 PK 参数（Cmax、Tmax、AUC、t1/2、]等）（在获得的数据允许的情况下）。