Browsing by Author "Jett, Rachel"

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    Paper spray mass spectrometry for rapid drug screening
    (2017-08) Jett, Rachel; Manicke, Nicholas; Goodpaster, John; McLeish, Michael
    Paper spray mass spectrometry is an alternative technique for toxicological screening that is able to quickly and adequately screen for compounds encountered in postmortem investigations with little sample handling and no sample preparation. For analysis of dried blood spots using a triple quadrupole mass spectrometer, detection criteria were defined to align with relevant regulatory guidelines while considering how fragment ion selection, method sensitivity, and fragment ion ratio tolerances are best utilized in paper spray mass spectrometry. For analysis, drugs and drug metabolites relevant to postmortem investigations were spiked into drug-free blood, and by monitoring two fragment ion channels in selected reaction monitoring mode, as well as the ratio between the two fragment ions, a method was developed capable of detecting over 120 drug and drug metabolites at concentrations relevant to postmortem drug screening. Total analysis time for the developed method is less than 8 minutes, and less than 50µL of sample and 5mL of solvent are consumed during analysis.
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    Toxicological Drug Screening using Paper Spray High-Resolution Tandem Mass Spectrometry (HR-MS/MS)
    (Oxford, 2018-06) McKenna, Josiah; Jett, Rachel; Shanks, Kevin; Manicke, Nicholas E.; Chemistry and Chemical Biology, School of Science
    Immunoassays and high-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) are both widely used methods for drug screening in toxicology. We investigated an alternative approach for rapid drug screening: paper spray MS (PS-MS). In paper spray, the biofluid sample is spotted onto a paper substrate. Upon application of a spray solvent and an electric potential, extraction and ionization occur directly from the paper without any need for additional sample preparation. We developed two paper spray high-resolution MS/MS targeted drug screening assays using a quadrupole-orbitrap mass spectrometer, one the positive ion mode and one in the negative ion mode. In the positive ion mode, over 130 drugs and drug metabolites were semi-quantitatively screened at sub-toxic concentrations in a single 2.5 min analysis. Limits of detection and calibration performances for each target compound are reported. The PS-MS/MS assay was tested on authentic postmortem specimens, and its screening ability and semi-quantitative performance were evaluated against independent LC–MS-MS screening and confirmation assays with good agreement. The paper spray MS/MS showed good qualitative agreement with LC–MS-MS; the true positive rate of paper spray MS/MS was 92%, and the true negative rate was over 98%. The quantitative results between the two methods were also acceptable for a screening application; Passing-Bablok regression yielded a slope of 1.17 and a Pearson’s correlation coefficient of 0.996. A separate PS-MS/MS negative ion screening method was also developed for a small panel of barbiturates and structural analogs, demonstrating its potential for acidic drug detection and screening.