Forensic drug screening by liquid chromatography hyphenated with high-resolution mass spectrometry (LC-HRMS)

Liquid chromatography-high resolution mass spectrometry (LC-HRMS) has been widely used for screening small organic molecules in complex samples. Its selectivity and sensitivity allow for broad-scope screening of thousands of analytes. However, the complexity of the acquired data has complicated its implementation in high-throughput laboratories that analyze hundreds of samples per week and require that multiple users be able to analyze the data. Forensic laboratories have managed to harvest the merits of LC-HRMS technology using robust and often leveled data analysis(/acquisition) workflows, without spending a disproportionate amount of time evaluating inconclusive or false positive identifications. This critical review describes the full analytical process of LC-HRMS-based forensic drug screening, from sample preparation to data analysis and beyond. Interesting solutions are highlighted, and two emerging trends will be discussed: i) the use of free online tools to improve forensic drug screening, and ii) re-use of data to improve forensic services. •Forensic drug screening should be scalable, flexible, and reproducible.•Levelling and tailoring improve data analysis workflows.•Caveats and false negative identifications must be identified.•Detection of new psychoactive substances are facilitated with free online tools.•Data re-use can augment forensic drug screening and services.