INSTRUMENT SYSTEM FOR RAPID HPLC/MS ANALYSIS OF DRUGS

这项拟议工作的目标是开发一种基于 飞行时间质谱仪和高效液体 专为快速和灵敏的分析而设计的色层分析技术 血液和尿液中的药物及其代谢物。这台仪器将会 使自动化药物筛选系统的未来发展成为可能 将在五分钟或更短时间内进行广谱药物分析， 使结果能够用于紧急诊断程序。 从高效液相色谱法洗脱出来的分析物将通过喷雾电离进行电离。 技术。将连续形成的离子转移到并存储 在一种独特的三维离子陷阱中，它们周期性地从 提取出来进行飞行时间质量分析。提取的离子到达 探测器在小于500微秒的间隔内，按其质量的顺序 在此期间，包含全质量光谱的瞬变信号 产生单位质量分辨率为m/z 2000或更大的信息。 积分瞬变记录器采集、求和和处理2000 从探测器每秒产生并记录10个瞬变信号 到每秒100个质谱图。这一过程的组合将 实现极高的灵敏度(检测下限小于10-9 摩尔)，因为在分析的每个阶段都非常有效地使用了样品 以及在高效液相色谱仪和 离子陷阱/飞行时间/质谱仪的高灵敏度和光谱产生率 使数据反卷积能够有效地应用于 层析未分解组分的鉴定与定量 组件。减少对层析分离的依赖，允许10- 将色谱运行时间缩短为原来的1倍或更多，而不会牺牲 敏感性或分析性信息。 组装的LC/MS系统将用于鉴定固定相， 运动阶段、仪器配置和实验 协议将最大限度地减少身份识别的分析时间和 血液中单一或混合药物及其代谢物的定量 和尿液，同时仍保持完全的分析完整性。LC/MS 寻求90-180秒的分析时间，从而实现广谱 目前需要在很短的时间内完成药物分析 必填项。最终目标将是描述组件和 将与LC/MS技术相结合以充分执行的过程 在适合诊断的时间范围内进行自动药物分析 有效性。

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.