Sensitive and Rapid Screening of Synthetic Drugs by Mass Spectrometry

通过质谱法灵敏快速地筛选合成药物

• 批准号: 9226136
• 负责人: Nicholas E Manicke
• 金额: $ 21.75万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9226136
• 关键词: Accident and Emergency department; Acute; Address; Adoption; Back; Biological Assay; Blood; Blood specimen; Cannabis; Chemical Structure; Chemicals; Chromatography; Clinic; Clinical; Collaborations; Complex; Data; Designer Drugs; Detection; Deterioration; Development; Devices; Drug abuse; Drug usage; Fentanyl; Future; Goals; Gold; Health; High Pressure Liquid Chromatography; Hospitalization; Hospitals; Human; Hybrids; Immunoassay; Indiana; Intoxication; Laboratories; Law Enforcement; Life; Link; Mass Spectrum Analysis; Measurement; Measures; Medical; Methods; New Agents; Paper; Paper Chromatography; Patients; Performance; Pharmaceutical Preparations; Pilot Projects; Plasma; Poison; Preclinical Drug Evaluation; Preparation; Prevalence; Public Health; Recording of previous events; Resolution; Risk; Running; Sampling; Solvents; Speed; Suggestion; Symptoms; System; Techniques; Technology; Test Result; Testing; Time; Toxic effect; Toxicology; Universities; Urine; Validation; acute toxicity; base; cathinone; clinical effect; cross reactivity; drug use screening; experience; improved; insight; instrumentation; ionization; manufacturing process; mass spectrometer; medical complication; method development; point of care; prevent; screening; small molecule; synthetic cannabinoid; synthetic drug; tandem mass spectrometry; tool; virtual; wasting

Project Summary Synthetic, or designer, drugs represent a serious public health risk. Compared to the traditional drugs for which they are sold as substitutes, synthetic drugs are often more potent and can result in life-threatening medical complications. One of the difficulties in preventing complications from synthetic drugs is that they go undetected by routine drug screens used in hospitals. Clinicians are therefore unaware of what the patient took. Moreover, determining when new synthetic drugs hit the street and whether there are complications related to their abuse is delayed. While samples can be sent to reference laboratories for testing, the results often do not come back for days or weeks making the tests of little help for the involved clinicians and are therefore rarely sent. Mass spectrometry is an attractive option for performing synthetic drug screens because it is sensitive, selective, and is a platform technology that can adapted relatively quickly as new agents emerge. The use of mass spectrometry for this purpose at or near the point of care is limited, however, due to the complexity of the analyses. The focus of this proposal is to simplify the entire analytical workflow required to perform mass spectrometric assays in order to make the use of MS assays more feasible for rapid screening of synthetic drugs. The core technology in the proposal is paper spray mass spectrometry, a direct analysis method in which biofluids samples such as blood can be analyzed directly without sample preparation. All of the components needed to perform the extraction and ionization of analytes from complex matrices can be contained within an inexpensive disposable cartridge. No sample preparation is performed, no solvent waste is generated, and no carry-over or clogging occur. These advantages make paper spray MS an attractive option for synthetic drug screening. The sensitivity of paper spray MS needs to be improved by about an order of magnitude to make it adequate for screening synthetic cannabinoids and fentanyl derivatives, however. In this proposal, we aim to develop and test a disposable paper spray cartridge that can dramatically improve the sensitivity of paper spray MS without increasing the complexity of the analysis. The general approach is to perform analyte preconcentration and separation from the sample matrix automatically on an inexpensive disposable cartridge, one requiring no special device or human action. We will also begin testing these methods on blood samples of patients presenting to the Emergency Department who are suspected to have used synthetic drug.

项目摘要 合成或设计的药物代表着严重的公共健康风险。与传统药物相比 作为替代品出售的合成药物通常更有效，可能会导致生命危险 医疗并发症。预防合成药物并发症的困难之一是它们会 未被医院使用的常规药物筛查发现。因此，临床医生不知道患者服用了什么。 此外，确定新的合成药物何时上市以及是否存在与 他们的虐待被推迟了。虽然样品可以被送到参考实验室进行检测，但结果往往不会 回来几天或几周，对相关的临床医生几乎没有帮助，因此很少 已发送。质谱学是进行合成药物筛选的一个有吸引力的选择，因为它很敏感， 选择性，是一种平台技术，可以随着新代理的出现而相对较快地适应。对.的使用 然而，在护理点处或附近用于此目的的质谱学是有限的，因为 分析。这项建议的重点是简化执行大量工作所需的整个分析工作流程 光谱分析，以使MS分析更适用于合成药物的快速筛选。 该提案中的核心技术是纸喷雾质谱仪，这是一种直接分析方法，其中 血液等生物流体样本可以直接分析，而不需要样品制备。所有的组件 从复杂的基质中提取和电离分析物所需的物质可以包含在 廉价的一次性墨盒。不进行样品制备，不产生溶剂浪费，不 发生结转或堵塞。这些优点使纸喷雾MS成为合成药物的一个有吸引力的选择 放映。喷纸MS的灵敏度需要提高大约一个数量级才能使其 然而，足以筛选合成大麻素和芬太尼的衍生物。在这项建议中，我们的目标是 开发并测试一种可显著提高纸张喷雾敏感性的一次性喷纸墨盒 MS，而不会增加分析的复杂性。一般的方法是进行分析物 在廉价的一次性盒上自动从样品基质中预浓缩和分离， 一种不需要特殊设备或人工操作的装置。我们还将开始对这些方法进行血样测试。 到急诊科就诊的疑似使用合成药物的病人。