A High Throughput Platform for Multiplexed Screening of Drugs of Abuse by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry

多段注射-毛细管电泳-质谱法多重筛查滥用药物的高通量平台

• 批准号: 501959-2016
• 负责人: BritzMcKibbin, Philip
• 金额: $ 8.92万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Idea to Innovation
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=609048
• 关键词: Throughput; Platform; Multiplexed; Screening; Drugs

New technologies are urgently required for more accurate yet reliable screening of drugs of abuse (DoA) given the worldwide epidemic of addiction to pain relief opioids and other classes of prescription medications. The socioeconomic impacts to the prescription drug abuse problem in Canada has been devastating to public health care and the criminal justice system, including mental illness and substance abuse, lost productivity, and an alarming increase in deaths due to drug overdose, such as the highly potent synthetic opioid, fentanyl. This project will introduce a high throughput platform for multiplexed screening of DoA in urine samples using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) that is suitable for implementation within an accredited clinical or forensic toxicology laboratory. Current approaches for primary screening of DoA rely on immunoassays that are prone to false positives and false negatives due to poor selectivity, which are not applicable to emerging classes of drugs due to the unavailability or long delays to access of viable antibody reagents that target only a single drug. Although liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used for confirmatory testing of screen-positive urine samples, it is not suitable for primary screening due its lower sample throughput and targeted nature of chemical analysis. We will overcome these limitations by optimizing and rigorously validating a patented screening technology based on MSI-CE-MS that relies on serial injections of up to ten urine samples within a single run (< 3 min/sample), where multiplexed electrophoretic separations are coupled to high resolution, accurate MS with full-scan data acquisition using a time-of-flight mass analyzer. This approach will offer a more selective, precise and less costly format for primary screening with high data fidelity, which will also enable unambiguous identification and detection of virtually an unlimited panel of DoA above accepted cut-off limits. Non-targeted drug screening based on MSI-CE-MS will also enable the discovery of new classes of lethal opioid analogs in adulterated or laced street drugs consumed at great risk by end-users. This innovative technology will introduce a superior screening platform to conventional immunoassays as required for more effective therapeutic drug monitoring programs and improved patient care while preventing drug diversion and tragic cases of accidental drug overdose.

鉴于全球范围内对止痛阿片类药物和其他类别处方药成瘾的流行，迫切需要新技术来更准确而可靠地筛查滥用药物（DoA）。加拿大处方药滥用问题的社会经济影响对公共卫生保健和刑事司法系统造成了毁灭性的影响，包括精神疾病和药物滥用，生产力下降，以及由于药物过量（如强效合成阿片类药物芬太尼）导致的死亡人数惊人增加。该项目将引入一个高通量平台，用于使用多段注射-毛细管电泳-质谱法（MSI-CE-MS）对尿液样本中的DoA进行多重筛选，该平台适用于经认可的临床或法医毒理学实验室。目前用于DoA的初级筛选的方法依赖于免疫测定，其由于选择性差而易于出现假阳性和假阴性，由于无法获得或长时间延迟获得仅靶向单一药物的可行抗体试剂，其不适用于新兴类别的药物。尽管液相色谱-串联质谱法（LC-MS/MS）用于筛查阳性尿液样本的确认检测，但由于其样本通量较低和化学分析的目标性，它不适合初步筛查。我们将通过优化和严格验证基于MSI-CE-MS的专利筛选技术来克服这些限制，该技术依赖于在单次运行中连续注射多达10个尿样（< 3分钟/样品），其中多路电泳分离与高分辨率，准确的MS结合，使用飞行时间质量分析仪进行全扫描数据采集。这种方法将提供一种更具选择性、更精确和成本更低的格式，用于具有高数据保真度的初级筛选，这也将能够明确识别和检测高于公认截止限值的几乎无限的DoA组。基于MSI-CE-MS的非靶向药物筛选也将能够发现最终用户在很大风险下消费的掺假或掺杂街头毒品中的新类别的致命阿片类药物类似物。这项创新技术将为传统免疫分析引入一个上级筛查平台，以实现更有效的治疗药物监测计划和改善患者护理，同时防止药物转移和意外药物过量的悲惨病例。