Forensic Drug Screening Enhanced by Liquid Chromatography-High Resolution Mass Spectrometry (LC–HRMS)

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Combining liquid chromatography (LC) with high resolution mass spectrometry (HRMS) has led to incredibly detailed results in forensic drug screenings, though not without challenges.

Forensic drug screening is a critical task that requires the detection of small organic molecules in complex samples with a high degree of sensitivity and selectivity. The use of liquid chromatography-high resolution mass spectrometry (LC–HRMS) has significantly improved the forensic drug screening process in recent years. However, the complexity of the data obtained from LC–HRMS has led to challenges in implementing this technique in high-throughput laboratories.

LC–HRMS is a powerful analytical technique used to identify and quantify small organic molecules in complex samples. It combines the separation capabilities of liquid chromatography with the sensitivity and selectivity of high-resolution mass spectrometry. LC–HRMS is used in a variety of applications, including drug discovery, metabolomics, environmental analysis, and forensic science.

A recent critical review published in the TrAC Trends in Analytical Chemistry journal by Marie Mardal, from the University of Copenhagen in Denmark and University of Norway in Tromsø, Norway, described the full analytical process of LC–HRMS-based forensic drug screening (1). The review highlights the importance of scalable, flexible, and reproducible forensic drug screening methods.

The review also discusses the use of leveling and tailoring to improve data analysis workflows, and the need to identify caveats and false negative identifications in forensic drug screening. The detection of new psychoactive substances has been facilitated by free online tools that can be used to enhance forensic drug screening. Furthermore, data re-use can augment forensic drug screening and services.


LC–HRMS has significantly improved the accuracy and efficiency of forensic drug screening by allowing for broad-scope screening of thousands of analytes with high sensitivity and selectivity. However, it is essential to develop robust data analysis workflows to deal with the complexity of the data obtained from this technique.

In conclusion, the review by Mardal provides insight into the current state of forensic drug screening by LC–HRMS, highlights interesting solutions to improve the screening process, and discusses emerging trends in this field. The use of LC–HRMS in forensic drug screening is expected to continue to grow, and the development of new data analysis workflows and tools will further enhance the accuracy and efficiency of this critical process.


(1) Heinsvig, P. J.; Noble, C.; Dalsgaard, P. W.; Mardal, M. Forensic drug screening by liquid chromatography hyphenated with high-resolution mass spectrometry (LC–HRMS). Trends Analyt Chem, 2023, 162, 117023. DOI: