Traditional immunoassay (IA)-based drug screens are limited in their scope of analysis and specificity. Their reliance on the cross-reactivity of antibody reagents is a limiting factor, particularly in light of the emergence of new therapeutics, emerging drugs, and new psychoactive substances (NPS). High resolution mass spectrometry (HRMS)-based techniques can offer improved versatility and specificity and increase the scope of analytical testing. In this study, a validated HRMS screening procedure was used to reanalyze adjudicated blood samples previously tested by immunoassay. IA methods employed enzyme-linked immunosorbent assay (ELISA) and enzyme multiplied immunotechnique (EMIT®). The comprehensive HRMS screen utilized supported liquid extraction (SLE) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Specimens previously tested by IA were reanalyzed using the HRMS screen following long term storage. The LC-QTOF-MS toxicology screen produced an additional 709 positive drug findings (67 compounds) among a population of 919 previously analyzed blood specimens. This study highlights the analytical benefits of MS-based toxicological screening and the advantages of data acquisition modalities that permit retrospective data interrogation. (Publisher abstract provided.)
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