Impact of sample preparation and analytical procedures on the comprehensive identification and measurement of LC-amenable food contact chemicals migrating from recycled paper food contact materials

• Migration is more effective in recovering tributyl phthalate and ethylparaben. • Direct injection at 5 μL boosts accuracy for bisphenols, PFOS, and phthalates. • Reconstitution reduces analyte quantities. • Distinct chemical profiles were revealed for migration and extraction. The chemical safety of food contact materials (FCMs), particularly those made from recycled paper, is a critical concern due to the potential migration of harmful substances into food. This study employed migration and exhaustive extraction methodologies to evaluate the impact of sample preparation techniques, such as evaporation, reconstitution, solvent selection, and injection volumes, on the identification of non-volatile food contact chemicals (FCCs) via liquid chromatography-high resolution mass spectrometry (LC-HRMS). Exhaustive extraction recovered a broader range of analytes, capturing compounds under extreme conditions, while migration yielded less pronounced results. However, certain chemicals, such as tributyl phthalate and ethylparaben were more effectively recovered under migration conditions. Direct injection at a 5 μL volume minimized analyte loss, enhancing detection accuracy for key substances such as bisphenols, perfluorooctanesulfonate (PFOS), and phthalates. Variations in sample preparation methods significantly influenced the extraction of LC-amenable compounds, with reconstitution found to reduce the signal of certain analytes. The inclusion of analytical blanks was critical in identifying and controlling background contamination. Principal Component Analysis (PCA) further revealed distinct profiles between migration and exhaustive extraction samples, highlighting the complementary nature of these approaches. This research supports the development of safer practices in FCM production and hazard analysis.