High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection–Capillary Electrophoresis–Mass Spectrometry

Autores

Alicia DiBattista†, Dianne Rampersaud‡, Howard Lee‡, Marcus Kim§, and Philip Britz-McKibbin*† † Department of Chemistry and Chemical Biology, McMaster University, Hamilton L8S 4L8, Canada ‡ Seroclinix Corporation, Mississauga, ON L4W 5B9, Canada § Agilent Technologies Inc., Mississauga, ON L5N 5M4, Canada *E-mail: britz@mcmaster.ca.

Abstract

New technologies are urgently required for reliable drug screening given a worldwide epidemic of prescription drug abuse and its devastating socioeconomic impacts on public health. Primary screening of drugs of abuse (DoA) currently relies on immunoassays that are prone to bias and are not applicable to detect an alarming array of psychoactive stimulants, tranquilizers, and synthetic opioids. These limitations impact patient safety when monitoring for medication compliance, drug substitution, or misuse/abuse and require follow-up confirmatory testing by more specific yet lower throughput instrumental methods. Herein, we introduce a high throughput platform for nontargeted screening of a broad spectrum of DoA and their metabolites based on multisegment injection–capillary electrophoresis–mass spectrometry (MSI–CE–MS). We demonstrate that MSI–CE–MS enables serial injections of 10 samples within a single run (<3 min/sample) where multiplexed electrophoretic separations are coupled to high resolution MS with full-scan data acquisition. Unambiguous drug identification was achieved by four or more independent parameters, including comigration with a deuterated internal standard or in silico prediction of electromigration behavior together with accurate mass, most likely molecular formula, as well as MS/MS as required for confirmation testing. Acceptable precision was demonstrated for over 50 DoA at 3 concentration levels over 4 days (median coefficient of variance = 13%, n = 117) with minimal ion suppression, isobaric interferences, and sample carry-over (<1%). This approach offers a rapid yet accurate method for simultaneous detection and identification of DoA at their recommended screening cutoff levels in human urine while allowing for systematic surveillance, specimen verification, and retrospective testing of designer drugs that elude conventional drug tests.

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