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

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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.