INSTRUMENT SYSTEM FOR RAPID HPLC/MS ANALYSIS OF DRUGS

用于药物快速 HPLC/MS 分析的仪器系统

• 批准号: 2187485
• 负责人: CHRISTIE G ENKE
• 金额: $ 11.05万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2187485
• 关键词: biomedical equipment development; drug detection; high performance liquid chromatography; mass spectrometry

The aim of the proposed work is to develop an instrument system based on time-of-flight mass spectrometry (TOF-MS) and high performance liquid chromatography (HPLC) specifically for the rapid and sensitive analysis of drugs and their metabolites in blood and urine. This instrument will enable the future development of an automated drug-screening system that will conduct wide-spectrum drug analyses in five minutes or less, enabling the results to be used in emergency diagnostic procedures. Analytes eluting from the HPLC will be ionized by a spray ionization technique. The continuously formed ions are transferred to, and stored in, a unique three-dimensional ion trap from which they are periodically extracted for time-of-flight mass analysis. Extracted ions arrive at the detector, in order of their mass, over an interval of less than 500 mus during which time, a transient signal containing full mass spectral information with unit mass resolution to m/z 2000 or greater is produced. An integrating transient recorder acquires, sums, and processes the 2000 transient signals per second from the detector to produce and record 10 to 100 mass spectra per second. This combination of processes will achieve extremely high sensitivity (detection limits of less than 10-9 mole) due to the very efficient use of sample in each stage of analysis and the compacting of analyte response that occurs in the HPLC and the ion-trap/TOF/MS. The high sensitivity and spectral generation rates enable the effective application of data deconvolution for the identification and quantitation of chromatographically unresolved components. Reduced reliance on chromatographic separation allows 10- fold or more reduction in chromatographic run time with no sacrifice in sensitivity or analytical information. The assembled LC/MS system will be used to identify the stationary phase, the moving phase, the instrumental configuration, and the experimental protocol that will minimize the analysis time for the identification and quantitation of single or mixed drugs and/or their metabolites in blood and urine while still maintaining full analytical integrity. An LC/MS analysis time of 90-180 seconds is sought, enabling a broad spectrum analysis of drugs to be accomplished in a fraction of the time presently required. A final objective will be to delineate the components and processes that will combine with the LC/MS technique to perform fully automated drug analyses in a time frame suitable for diagnostic effectiveness.

拟议工作的目的是开发一个仪器系统的基础上， 飞行时间质谱（TOF-MS）和高效液相色谱 高效液相色谱（HPLC），专门用于快速和灵敏的分析 血液和尿液中药物及其代谢物的含量。 该工具将 使自动药物筛选系统的未来发展成为可能， 将在五分钟或更短的时间内进行广谱药物分析， 使得结果能够用于紧急诊断过程。 从HPLC洗脱的分析物将通过喷雾电离进行电离 法 连续形成的离子被转移到 在独特三维离子阱中，它们周期性地 提取用于飞行时间质量分析。 提取的离子到达 在小于500 μ s的时间间隔内，按质量排列的探测器 在此期间，包含全质谱的瞬态信号 产生具有m/z 2000或更高的单位质量分辨率的信息。 一个集成的瞬态记录仪采集、求和并处理2000个 从检测器产生并记录每秒的瞬态信号10 到每秒100个质谱 这些过程的组合将 实现极高的灵敏度（检测限小于10-9 摩尔），这是由于在分析的每个阶段都非常有效地使用了样品 以及在HPLC中发生的分析物响应的压缩， 离子阱/飞行时间/质谱。高灵敏度和光谱产生率 使数据反褶积的有效应用， 鉴别和定量色谱上未分离的 件. 减少对色谱分离的依赖， 色谱运行时间缩短1倍或更多， 敏感性或分析信息。 组装的LC/MS系统将用于鉴别固定相， 移动相，仪器配置和实验 将最大限度地减少识别分析时间的方案， 血液中单一或混合药物和/或其代谢物的定量 和尿液，同时仍然保持完整的分析完整性。 的LC/MS 90-180秒的分析时间是寻求， 药物分析将在目前的一小部分时间内完成 必需的. 最后一个目标将是界定各组成部分， 将联合收割机与LC/MS技术相结合， 在适合诊断的时间范围内进行自动化药物分析 有效性