Advances with Solid Substrate Spray Mass Spectrometry for Quantitative Illicit Drug Measurement
Date
2023-08-28
Authors
Laxton, John-Clare
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Abstract
The opioid crisis continues to be the leading cause of overdose and death among people who use drugs (PWUD). Harm reduction drug checking (HRDC) services aimed at preventing accidental overdose events do so by offering pre-consumption chemical measurements to help PWUD make informed decisions regarding a drug they intend to use. Conventional on-site drug checking technologies such as immunoassay test strips, colorimetry test strips, FT-IR, and portable Raman spectroscopy results do not possess adequate sensitivity for trace levels of toxic drugs, and/or the selectivity to detect newly emerging threats as they appear in the illicit drug supply. Chapter 1 of this thesis provides background information, as well as framework to why mass spectrometry (MS) is the ideal candidate for the analytical task of quantitative HRDC. Solid-substrate electrospray ionization (ESI) was developed as a rapid and direct ionization method for the qualitative and quantitative analysis of complex samples with little to no sample preparation. In this thesis, paper spray mass spectrometry (PS-MS) and paper capillary spray ionization (PCSI), two derivatives of solid-substrate ESI, were utilized for quantitative illicit drug measurements.
Conventional (quantitative) chemical analysis requires samples to be sent to centralized laboratories with the requisite supporting infrastructure, however, innovations to the field of portable MS has revolutionized the paradigm of real-time chemical analysis by bringing the laboratory to the sample, answering chemical questions when and where they are needed. In Chapter 2 of this thesis, a simple, rapid, and quantitative ambient ionization tandem mass spectrometry method was developed and implemented for the analysis of real-world illicit drug samples utilizing a miniature mass spectrometer system. The performance, characterization, and improvement of a portable/miniature mass spectrometer (based on a rectilinear quadrupole ion trap) was initially characterized using legally exempt test kit drug standards. A novel spray solvent addition system was developed to improve inter- and intra-day reproducibility, calibration linearity, and analytical sensitivity. The system was then evaluated as a potential on-site, rapid, point-of-care chemical diagnostic system to identify and quantify illicit drug analytes. Target analytes were detected and quantified via PCSI-MS/MS for samples where conventional on-site drug checking technologies were not always effective.
In Chapter 3 of this thesis, various internal standard (ISTD) utilization strategies were evaluated with the goal of simplifying HRDC PS-MS quantitative measurements while drastically reducing waste. This was achieved by depositing ISTDs on PS-MS strips, pre- and post-sample deposition, to evaluate its quantitative performance of illicit drug analytes. Pre-sample ISTD depositions reduce disruptions in (PS-MS) HRDC services due to ISTD supply/integrity and improves turnaround time for chemical analysis; all of which reduce analytical costs (i.e., ISTD consumables, labor costs, solvent) for real world samples. Post-sample ISTD depositions offer the ability to send in-field samples to off-site laboratories for appropriate ISTD deposition. A parallel study assessed the analytical performance of delivering 1 nanogram of ISTD per paper strip by one of two methods: 1) the conventional method by “Hand”, depositing volumes with a mechanical micropipette, and 2) by “Robot” through the assistance of a robotic liquid handling system. The goal of this thesis is to promote the feasibility and wide-spread adoption of solid-substrate spray-based MS technology as an on-site HRDC tool.
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Keywords
Paper Spray Mass Spectrometry, Quantitative Harm Reduction Drug Checking