ULTRATRACE DRUG ANALYSIS USING THE QUADRUPOLE ION TRAP

使用四极离子阱进行 ULTRATRACE 药物分析

• 批准号: 3438510
• 负责人: ROBERT C DOREY
• 金额: $ 5.54万
• 依托单位: WICHITA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438510
• 关键词: anticonvulsants; antidepressants; fluphenazine; human therapy evaluation; mental disorder chemotherapy; nervous system disorder chemotherapy; pharmacokinetics; plasma; tranquilizer

Novel methods are proposed for monitoring of therapeutic drugs which are present in plasma at extremely low concentrations. Many important drugs both exhibit wide-ranging effects and are present near or below the limit of detection of available analytical techniques. Gas chromatography/chemical ionization mass spectrometry (GC/CIMS) and gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS) provide the sensitivity and specificity needed for extremely low-level drug analysis, but equipment cost precludes their widespread use. This proposal concerns the development of GC/CIMS and GC/MS/MS techniques using the quadrupole ion trap (QUIT) for applications in trace-level drug analysis. The physical characteristics of the QUIT make it inherently suitable for such techniques. The mechanical simplicity of the instrument also reduces its cost far below standard GC/CIMS and GC/MS/MS instruments. These two techniques will provide lower detection limits and better discrimination against interfering compounds than standard gas chromatography/(electron ionization) mass spectrometry (GC/MS), currently the method of choice for trace drug analysis. Model compounds for this project are drugs used in psychiatric practice. These drugs are prime candidates for therapeutic monitoring because of their ability to simultaneously affect several systems within the brain. However, many are also present in plasma at levels near or below the limits of detection of available assay methods. The new techniques will first be demonstrated with the tricyclic antidepressants and antiepileptics, which can be measured by GC/MS. The low-level neuroleptics fluphenazine, fluphenazine decanoate, trifluoperazine, and thiothixene are present in plasma at concentrations too low to be measured reliably by GC/MS, and analysis of these compounds by the above techniques will be an essential step in understanding their function and more effective therapeutic use.

提出了用于监测治疗药物的新方法， 在血浆中以极低浓度存在。 许多重要药物 两者都表现出广泛的影响，并且接近或低于极限 检测可用的分析技术。 气体 色谱/化学电离质谱（GC/CIMS）和气相色谱 色谱/质谱/质谱（GC/MS/MS）提供了 极低水平药物分析所需的灵敏度和特异性， 但是设备成本阻碍了它们的广泛使用。 本建议涉及GC/CIMS和GC/MS/MS技术的发展 使用四极离子阱（QUIT）用于痕量级药物 分析. 退出的物理特性使其固有的 适合这种技术。 该仪器的机械简单性 其成本远低于标准GC/CIMS和GC/MS/MS仪器。 这两种技术将提供更低的检测限和更好的 与标准气体相比，对干扰化合物的鉴别 色谱/（电子电离）质谱（GC/MS），目前 痕量药物分析的首选方法。 该项目的模型化合物是用于精神病学实践的药物。 这些药物是治疗监测的主要候选药物，因为 他们同时影响大脑中几个系统的能力。 然而，许多也存在于血浆中的水平接近或低于限度 检测可用的分析方法。 新技术将首先 三环类抗抑郁药和抗癫痫药， 可以通过GC/MS测量。低水平的精神抑制剂氟奋乃静， 氟奋乃静癸酸酯、三氟拉嗪和硫代噻吨存在于 血浆浓度过低，无法通过GC/MS可靠测量，以及 通过上述技术分析这些化合物将是必不可少的 进一步了解它们功能和更有效的治疗用途。