Mass spectrometry is the most powerful and flexible analytical tool we have for both broad and in-depth analysis of lipids, allowing for the discovery of novel biomarkers and the elucidation of pathomechanisms and therapeutic targets in the context of disease. However, for the capabilities of this technology to be translated to the clinical setting, several challenges need to be overcome, such as the reproducible identification and quantification of lipids between laboratories. This would allow us to establish reference intervals for individual lipids, which clinicians rely on for interpreting results and making diagnoses. For this, standardization of mass spectrometry data acquired on multiple different platforms needs to be achieved. This work sought to address this need by having 34 different laboratories measure the molar concentrations of a given set of individual ceramide species in the same 4 plasma samples. The goal was to assess the accuracy and concordance between the different platforms and protocols used and highlight the issues which may give rise to variability in the measured concentrations.

This community effort was the largest inter-laboratory and cross-platform standardization trial using human plasma to date. This work was able to demonstrate that lipid mass spectrometry data can be highly reproducible when the same normalization techniques and labelled standards are used, regardless of the sample preparation/lipid extraction method, separation technique, and type of mass spectrometer used. This study lays the foundation for determining reference values in diverse populations and different disease conditions that will advance our knowledge of the roles ceramides play in health disease and bring us a step forward to the use of mass spectrometry in the clinic.

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