- A novel ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed to enable the analysis of ultra-low levels of lignin phenols (<100fmol) in environmental samples. The method included a sample clean-up with a polymer sorbent based solid-phase extraction and reversed-phase chromatography that allowed separation of all lignin phenols with minimal interference from co-eluting matrix components. The application of 13C-labeled surrogate standards effectively compensated for variability associated with sample preparation and ion suppression. The method was fully validated and compared to gas chromatography-electron impact ionization-tandem mass spectrometry for Suwannee River humic acid standard reference material and extracted riverine dissolved organic matter. The comparison demonstrated the robustness and suitability of the method for ultra-low lignin phenol concentrations and high matrix interference. The simple and fast sample preparation coupled to analysis without derivatization makes it feasible for routine and high-volume analyses.