NOVEL METHOD FOR RAPID SEPARATION AND DETECTION OF DRUGS

描述：（申请人摘要） PI最近开发了一种超快速，高分辨率的方法， 滥用药物和相关化合物的分析测定。 基于 电喷雾离子化与离子迁移率分离和质谱 检测，该方法分离的化合物的分辨率相当 传统的色谱方法在毫秒时间尺度上， 检测限类似于气相色谱法后可能的检测限。 在 色谱术语，理论塔板数大于20万， 在小于一秒的时间内测量，伴随的板高度为600 nm 检测限小于1 ppb（ng/mL）。 虽然离子迁移率 光谱测定法已被常规地用于挥发性物质的街道检测。 药物滥用，它一直不符合检测极性和 生物基质中的非挥发性药物。 这项拨款申请提出 评价电喷雾/离子迁移谱/质谱 (ESI/IMS/MS）作为一种快速灵敏的测量分析方法 从复杂的基质中提取滥用药物， 用于测量阿片样物质和其它肽的构象状态的仪器 兴趣 该项目分为三个阶段，1）评估 ESI/IMS/MS作为定量分析的快速分离和检测装置 和从液体样品中定性确定滥用药物; 2） 二次电喷雾离子化/IMS/MS作为测定 从蒸气样品中测定滥用药物：和3）构象异构体 目的肽的表征和异构体分离。 此外 对于独立的装置，仪器将连接到液体和 气相色谱 该项目的成功完成不仅 产生用于快速定量的分析方法， 查明滥用药物，而且还将提供一种研究工具， 可以直接与体内透析实验结合或用于获得 高分辨率的空间和时间药物浓度分布， 细胞外间隙

DESCRIPTION: (Applicant's Abstract) The PI has recently developed an ultra-rapid, high-resolution method for the analytical determination of drugs of abuse and related compounds. Based on electrospray ionization with ion mobility separation and mass spectrometric detection, this method separates compounds with resolving powers comparable to traditional chromatographic methods on a millisecond time scale and with detection limits similar to that possible after gas chromatography. In chromatographic terms, theoretical plate numbers larger than 200,000 have been measured in less than a second with concomitant plate heights of 600 nm at detection limits less that 1 ppb (ng/mL). While ion mobility spectrometry has been routinely used for the street detection of volatile drugs of abuse, it has not been compatible with the detection of polar and non-volatile drugs in biological matrices. This grant application proposes to evaluate electrospray/ion mobility spectrometry/mass spectrometry (ESI/IMS/MS) as an analytical method for the rapid and sensitive measurement of drugs of abuse from complex matrixes and as a fundamental research instrument to measure conformational states of opioid and other peptides of interest. The project is divided into three phases, 1) the evaluation of ESI/IMS/MS as a rapid separation and detection device for the quantitative and qualitative determination of drugs of abuse from liquid samples; 2) the evaluation of secondary electrospray ionization/IMS/MS as a method for the determination of drugs of abuse from vapor samples: and 3) conformer characterization and isomer separation of peptides of interest. In addition to a stand-alone device the instrument will be coupled to both liquid and gas chromatography. Successful completion of the project will not only result in an analytical method for the rapid quantification and identification of drugs of abuse, but will also provide a research tool that can be coupled directly to in vivo dialysis experiments or used to obtain highly resolved spatial and temporal drug concentration profiles in extracellular space.