Pseudoenhanced Peak Efficiency in Liquid Chromatography-High Resolution Mass Spectrometry Using Multiple Second Derivatives

A mathematical approach is introduced to achieve pseudoenhanced peak efficiency in liquid chromatography-high resolution mass spectrometry (LC-HRMS¹), utilizing second-derivative transformations with respect to time and Gaussian smoothing cycles. The pipeline involved interpolating all MS scans, recorded as profile scans, onto a common m/z axis, allowing for second-derivative transformations for each m/z increment with respect to time across the entire data set. Validation using a public study (comprising 1100 compounds analyzed on a Thermo Q Exactive) demonstrates substantial improvements in feature detection and resolution, with qualitative and quantitative benefits. The transformation enables increased peak efficiency by up to 2 orders of magnitude in multicycle implementations without requiring physical hardware enhancements. The approach provides enhanced separation of complex mixtures, reduced background contributions, and increased reliability in untargeted metabolomics and related analyses.