From promise to practice: why HRMS has yet to fully revolutionize forensic toxicology

Dear Co-Editors,

High-resolution mass spectrometry (HRMS), including quadrupole time-of-flight (QTOF) and Orbitrap mass spectrometry techniques, holds great promise for advancing forensic toxicology beyond the capabilities of nominal mass instrumentation. Manufacturers have excelled on improving physical instrument hardware parameters to increase sensitivity, resolution, robustness, and scanning speed performance, paired with the implementation of novel mass acquisition modes. These aspects are indeed critical, and current models seemingly have met these hardware needs for forensic toxicology applications. However, despite its potential, routine applications of HRMS in forensic laboratories remain largely confined to a targeted scope (or variations thereof), rather than its full intended capability: untargeted detection of unknown analytes with retrospective identification of unexpected and emerging substances. This limitation is not due to physical technological constraints but rather a lack of efficient software and data processing solutions from HRMS instrument manufacturers to enable handling of vast and complex datasets acquired through untargeted analysis. Furthermore, computational demands of such data-intensive processing require high-performance computers and data storage, yet many instruments lack the necessary computer hardware to efficiently handle the workload...